Ministry of Health | Manatū Hauora

Immunisation Handbook
2017

Disclaimer

This publication, which has been prepared for, and is published by, the Ministry of Health, is for the assistance of those involved in providing immunisation services in New Zealand.

While the information and advice included in this publication are believed to be correct, no liability is accepted for any incorrect statement or advice. No person proposing to administer a vaccine to any other person should rely on the advice given in this publication without first exercising his or her professional judgement as to the appropriateness of administering that vaccine to another person.

Feedback

Comments on this book and suggestions for future editions are invited, to enhance the usefulness of future editions. These should be sent to the Manager Immunisation, Ministry of Health, at the address below.

Citation: Ministry of Health. 2017. Immunisation Handbook.
Wellington: Ministry of Health.

First published in May 2017
by the Ministry of Health
PO Box 5013, Wellington 6140, New Zealand

ISBN: 978-1-98-850251-9 (print)
ISBN: 978-1-98-850252-6 (online)
ISBN: 978-1-98-850253-3 (ebook)
HP 6600

This document is available on the Ministry of Health website.

CCBY This work is licensed under the Creative Commons Attribution 4.0 International licence. In essence, you are free to: share ie, copy and redistribute the material in any medium or format; adapt ie, remix, transform and build upon the material. You must give appropriate credit, provide a link to the licence and indicate if changes were made.

Contents

Foreword

The Immunisation Handbook Advisory Group

Acknowledgements

Main source books

Commonly used abbreviations

Introduction

1 General immunisation principles

2 Processes for safe immunisation

3 Vaccination questions and addressing concerns

4 Immunisation of special groups

5 Diphtheria

6 Haemophilus influenzae type b (Hib) disease

7 Hepatitis A

8 Hepatitis B

9 Human papillomavirus (HPV)

10 Influenza

11 Measles

12 Meningococcal disease

13 Mumps

14 Pertussis (whooping cough)

15 Pneumococcal disease

16 Poliomyelitis

17 Rotavirus

18 Rubella

19 Tetanus

20 Tuberculosis

21 Varicella (chickenpox)

22 Zoster (herpes zoster/‌shingles)

Appendices

Appendix 1:The history of immunisation in New Zealand

Appendix 2:Planning immunisation catch-ups

Appendix 3:Immunisation standards for vaccinators and guidelines for organisations offering immunisation services

Appendix 4:Authorisation of vaccinators and criteria for pharmacist vaccinators

Appendix 5:Immunisation certificate

Appendix 6:Passive immunisation

Appendix 7:Vaccine presentation, preparation, disposal, and needle-stick recommendations

Appendix 8:High-incidence TB countries

Appendix 9:Websites

Funded vaccines for special groups

List of tables

List of figures

Foreword

With the publication of the Immunisation Handbook 2017 (the Handbook), it is once again appropriate to extend the Ministry of Health’s thanks to everyone involved in supporting, promoting or delivering immunisations to the people of New Zealand. This Handbook has been designed as a comprehensive source of information on immunisation, to support you in the work you do.

Since the July 2014 edition of the Handbook, there have been two subsequent editions ie, the 2014 (2nd ed) and 2014 (3rd ed) released online. Both of these editions were updated with a few amendments and PHARMAC’s revised eligibility criteria for some of the vaccines for individuals at increased risk of the relevant vaccine-preventable diseases.

On 1 January 2017, PHARMAC approved funding for human papillomavirus vaccine for boys and girls up to the age of 27 years, and these changes were included in the 2014 (3rd ed) online Handbook versions. From July 2017 varicella vaccine will be introduced to the National Immunisation Schedule and is expected to significantly reduce the burden of varicella disease, particularly in young infants.

Immunisation coverage has continued to improve and as at 31 December 2016, 93.3 percent of 8-month-olds and 93.1 percent of
2-year-olds were fully immunised for the quarter. Significant progress has been made for immunisation at age 5 years in recent years, with coverage increasing from 82 percent in June 2015 to 89 percent in December 2016. Gains have consistently been made for Māori infants and children, with an increase in coverage at age 8 months from 78 percent in 2012 to 91 percent in December 2016. In the Human Papillomavirus (HPV) Immunisation Programme, equity has continued to be achieved for young Māori and Pacific women, and 12 district health boards achieved or exceeded the 2016 HPV immunisation coverage target of 65 percent of 12‑year-old girls having received all three HPV doses.

At a population level, the effects of increasing immunisation coverage are clearly discernible, with fewer cases of vaccine-preventable diseases as coverage increases. In New Zealand, we have seen significant decline in hepatitis B, Haemophilus influenzae type b, genital warts and, in infants, pneumococcal and rotavirus diseases since the introduction of vaccines.

The health community deserves praise for this improvement, but at the same time must continue with its efforts to increase coverage toward the point where herd immunity against the most infectious diseases can be achieved.

I congratulate you on these past achievements and encourage your ongoing commitment to improving immunisation coverage and reducing vaccine-preventable diseases in New Zealand. Pharmacists can now assist with achieving this goal. Due to a reclassification of the influenza, meningococcal, Tdap and zoster vaccines, pharmacists who have undergone Ministry-approved vaccinator training can now administer these vaccines to adults. In 2017 pharmacists have also been able to provide funded influenza vaccinations to those aged 65 years and older and to pregnant women. This provides more opportunities for people to be vaccinated against these infectious diseases.

Immunisation is an important opportunity for health professionals to interact with people from all walks of life: mothers with newborns, school-age children, and adults either working or retired. Your attitude and the conversations you have with people affect their attitudes toward immunisation and their engagement with the health care system in general. We hope this Handbook will help your interactions with your patients and their families/whānau.

In closing, I would like to thank the members of the Handbook Advisory Group who updated the Handbook – and also all the peer reviewers. I trust this edition, like its predecessors, will prove a valuable resource for health professionals.

Chai Chuah
Director-General of Health and Chief Executive

The Immunisation Handbook Advisory Group

The Immunisation Handbook Advisory Group provided expert technical and medical advice for the Immunisation Handbook 2017. The Ministry of Health wishes to thank them for their time and commitment during the Handbook update and rewrite. The Handbook Advisory Group members are as follows.

Dr Caroline McElnay
Public Health Medicine Specialist and Medical Officer of Health

Dr Edwin (Gary) Reynolds
General Practitioner

Associate Professor Nikki Turner
Director, Immunisation Advisory Centre and General Practitioner

Dr Ayesha Verrall
Infectious Diseases Physician, Infectious Diseases Epidemiologist

Dr Tony Walls
Paediatrician and Infectious Diseases Specialist

Dr Elizabeth Wilson
Paediatric Infectious Diseases Specialist

Acknowledgements

The Ministry of Health (the Ministry) appreciates the time and commitment of those involved in the updating and rewriting of the Immunisation Handbook 2017.

Karin Batty, Emma Best, Tim Blackmore, Lynette Collis, Jim Faed, Bernadette Heaphy, Sue Huang, the Immunisation Advisory Centre, the Institute of Environmental Science and Research, Lance Jennings, Tomasz Kiedrzynski, Susan Kenyon, Min Lo, Liza Lopez, Andrea McNeill, Chris Millar, Diana Murfitt, Helen Petousis-Harris, Stewart Reid, Stephen Ritchie, Loretta Roberts, Rebekah Roos, Taylor Saunders, Lesley Voss and Rachel Webb.

The Ministry would especially like to acknowledge the work of Vikki Cheer, the Handbook medical writer.

Main source books

American Academy of Pediatrics. 2015. Red Book: 2015 Report of the Committee on Infectious Diseases (29th edition). Kimberlin DW, Brady MT, Jackson MA, et al (eds). Elk Grove Village, IL: American Academy of Pediatrics.

Department of Health and Ageing. 2016. The Australian Immunisation Handbook (10th edition, updated 2016). Canberra, ACT: Department of Health and Ageing.

Ministry of Health. 2012. Communicable Disease Control Manual 2012. Wellington: Ministry of Health.

Plotkin SA, Orenstein WA, Offit PA (eds). 2013. Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.

New Zealand epidemiology data

Information on New Zealand epidemiology is sourced from data collated by the Institute of Environmental Science and Research (ESR), on behalf of the Ministry of Health, or from Analytical Services, Ministry of Health.

For the most up-to-date epidemiological data, see the ESR (www.esr.cri.nz) and Ministry of Health (www.health.govt.nz/nz-health-statistics) websites.

Commonly used abbreviations

23PPV 23-valent pneumococcal polysaccharide vaccine
ADT adult diphtheria and tetanus vaccine
AEFI adverse event following immunisation
AFP acute flaccid paralysis
AIDS acquired immunodeficiency syndrome
AOM acute otitis media
BCG bacillus Calmette–Guérin vaccine
CARM Centre for Adverse Reactions Monitoring
CPR cardiopulmonary resuscitation
CRS congenital rubella syndrome
DHB district health board
DMARD disease-modifying anti-rheumatic drug
DNA deoxyribonucleic acid
DT diphtheria and tetanus vaccine
DTaP diphtheria, tetanus and acellular pertussis vaccine
DTaP-IPV diphtheria, tetanus, acellular pertussis and inactivated polio vaccine
DTaP-IPV-HepB/Hib diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B and Haemophilus influenzae type b vaccine
DTwP diphtheria, tetanus and whole-cell pertussis vaccine
DTwPH diphtheria, tetanus, whole-cell pertussis and Haemophilus influenzae type b vaccine
ESR Institute of Environmental Science and Research
GBS Guillain–Barré syndrome
GP general practitioner
GSK GlaxoSmithKline (New Zealand) Limited
HAV hepatitis A virus
HBcAg hepatitis B core antigen
HBeAg hepatitis B e antigen
HBIG hepatitis B immunoglobulin
HBsAg hepatitis B surface antigen
HBV hepatitis B virus
HepB hepatitis B vaccine
Hib Haemophilus influenzae type b
HIV human immunodeficiency virus
HPV human papillomavirus
HSCT haematopoietic stem cell transplant
HZ herpes zoster
HZV herpes zoster vaccine
ICD International Classification of Diseases
IG immunoglobulin
IgG immunoglobulin G
IM intramuscular
IMAC Immunisation Advisory Centre
IPD invasive pneumococcal disease
IPV inactivated polio vaccine
ITP idiopathic thrombocytopenic purpura (also known as immune thrombocytopenia)
IV intravenous
IVIG intravenous immunoglobulin
LAIV live attenuated influenza vaccine
MCV4-D quadrivalent meningococcal conjugate vaccine (conjugated to diphtheria toxoid)
Medsafe New Zealand Medicines and Medical Devices Safety Authority
MenCCV meningococcal C conjugate vaccine
MeNZB meningococcal B vaccine
MMR measles, mumps and rubella vaccine
MMRV measles, mumps, rubella and varicella vaccine
MSD Merck Sharp & Dohme (New Zealand) Limited
NHI National Health Index
NIR National Immunisation Register
NTHi non-typeable Haemophilus influenzae
NZBS New Zealand Blood Service
OPV oral polio vaccine
PCR polymerase chain reaction
PCV7 7-valent pneumococcal conjugate vaccine
PCV10 10-valent pneumococcal conjugate vaccine
PCV13 13-valent pneumococcal conjugate vaccine
PFU plaque-forming unit
PHARMAC Pharmaceutical Management Agency
PMS practice management system (also known as patient management system)
PRP polyribosylribitol phosphate
PSNZ Pharmaceutical Society of New Zealand
PTAC Pharmacology and Therapeutics Advisory Committee
RIG rabies immunoglobulin
RNA ribonucleic acid
RV1 rotavirus vaccine (monovalent)
RV5 rotavirus vaccine (pentavalent)
SBVS School-Based Vaccination System
SC subcutaneous
SCID severe combined immune deficiency
STI sexually transmitted infection
SUDI sudden unexpected death in infancy
TB tuberculosis
Td adult tetanus and diphtheria vaccine
Tdap adult tetanus, diphtheria and acellular pertussis vaccine
TIG tetanus immunoglobulin
TIV trivalent inactivated vaccine
UK United Kingdom
US United States of America
VAPP vaccine-associated paralytic poliomyelitis
VLP virus-like particle
VTC vaccinator training course
VV varicella vaccine
VZV varicella zoster virus
WHO World Health Organization
ZIG zoster immunoglobulin

Introduction

In this chapter:

Changes to the Handbook in 2017

The National Immunisation Schedule

Changes to the National Immunisation Schedule from 1 July 2017

2017 changes to targeted programmes for special groups

Eligibility for publicly funded vaccines

Notifiable diseases

The purpose of the Immunisation Handbook 2017 (the Handbook) is to provide clinical guidelines for health professionals on the safest and most effective use of vaccines in their practice. These guidelines are based on the best scientific evidence available at the time of publication, from published and unpublished literature.

Changes to the Handbook in 2017

All chapters have been updated and revised since the 2014 edition. The following changes have been made.

The National Immunisation Schedule

The National Immunisation Schedule (the Schedule) is the series of publicly funded vaccines available in New Zealand (see Table 1). Some vaccines are also offered as targeted programmes in response to a recognised need (see Table 2). See also section 2.1.7 for a summary of the primary immunisation requirements for adults (funded) and other funded and unfunded recommendations for this age group.

On 1 July 2012 the management and purchasing of vaccines transferred from the Ministry of Health to PHARMAC. All publicly funded vaccines are now listed on PHARMAC’s Pharmaceutical Schedule (see www.pharmac.govt.nz), and the district health boards (DHBs) are responsible for funding these once PHARMAC has listed them.

PHARMAC considers medicine and vaccine funding applications from pharmaceutical suppliers, health professionals, consumer groups and patients. Usually, manufacturers/suppliers decide whether to make an application for funding. Normally this will follow registration and approval of the medicine or vaccine by Medsafe. PHARMAC will generally only consider an application for a medicine or vaccine to be funded once it has been registered and approved by Medsafe.

Following a vaccine funding application, PHARMAC will assess the vaccine, seek clinical input (for vaccines this may be from the immunisation subcommittee of the Pharmacology and Therapeutics Advisory Committee [PTAC] or from PTAC itself), and conduct an economic analysis. The recommendations from the immunisation subcommittee are then considered by PTAC, who will provide advice to PHARMAC. PHARMAC then decides what priority the application has for funding, and consults with the Ministry of Health on capacity and implementation issues that may be associated with introducing a new vaccine. Depending on the outcome of that process, PHARMAC may then negotiate with the supplier. If an agreement is reached, PHARMAC will consult with the health sector on a funding proposal.

The Ministry of Health remains responsible for and manages the National Immunisation Programme. The National Immunisation Programme:

The Ministry of Health works with PHARMAC to ensure there is a strong link between vaccine decisions, management and the National Immunisation Programme.

Changes to the National Immunisation Schedule from 1 July 2017

Table 1 shows the 2017 National Immunisation Schedule, and Table 2 shows the vaccines funded for special groups at higher risk of some diseases.

Changes to vaccine funding from 1 July 2017 are as follows.

  1. One dose of varicella vaccine (VV, Varilrix; see chapter 21 ‘Varicella’) will be introduced for:
  2. The monovalent rotavirus vaccine (RV1, Rotarix) replaces the pentavalent rotavirus vaccine (RV5, RotaTeq). RV1 is administered as a two-dose schedule, at ages 6 weeks and 3 months (see chapter 17 ‘Rotavirus’).
  3. The 10-valent pneumococcal vaccine (PCV10, Synflorix) replaces the 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13) at age 6 weeks, and at ages 3, 5 and 15 months (see chapter 15 ‘Pneumococcal disease’).
  4. The measles, mumps and rubella vaccine (MMR, Priorix) replaces the previously used MMR vaccine (MMR-II; see chapter 11 ‘Measles’).
  5. The monovalent Haemophilus influenzae type b vaccine (Hib, Hiberix) replaces the previously used Hib vaccine (Act-HIB; see chapter 6Haemophilus influenzae type b disease’).
  6. The influenza vaccine for the 2017 influenza season will be the trivalent inactivated vaccine Influvac. The quadrivalent inactivated vaccine, Influvac Tetra, will be used from the first full influenza season following the vaccine’s registration.
Table 1: National Immunisation Schedule, commencing 1 July 2017
Antigen(s) DTaP-IPV-HepB/Hib PCV10 RV1 MMR Hib VV DTaP-IPV Tdap HPV9 Td Influenza
Brand Infanrix-hexa Synflorix Rotarix Priorix Hiberix Varilrix Infanrix-IPV Boostrix Gardasil9 ADT Booster Influvac
Manufacturer GSK GSK GSK GSK GSK GSK GSK GSK Seqirus/
MSD
Seqirus Mylan
Pregnancy               a    
6 weeks                
3 months                
5 months                  
15 months     b          
4 years                  
11 or 12 yearsc              
2 dosesc
   
45 years                    
65 years                  
annually
  1. Tdap is for women during every pregnancy, from 28 to 38 weeks’ gestation.
  2. VV is funded for children born on or after 1 April 2016.
  3. HPV is funded for individuals aged 26 years and under: 2 doses for those aged 14 years and under; 3 doses for those aged 15–26 years; 3 doses for those aged 9–26 years with certain medical conditions, plus an additional dose post-chemotherapy.

2017 changes to targeted programmes for special groups

Vaccines funded for special groups are described in Table 2 below. Changes to existing programmes from 1 July 2017 are as follows.

  1. Hepatitis B vaccine (HepB, HBvaxPRO; see chapter 8) will continue to be funded for individuals with eligible conditions. In addition, HepB will be funded for post-haematopoietic transplant patients.
  2. Pneumococcal conjugate vaccine (PCV13, Prevenar 13) and pneumococcal polysaccharide vaccine (23PPV, Pneumovax 23) continue to be available for eligible individuals. In addition, PCV13 and 23PPV will be available for children with specific high-risk conditions.
Table 2: Funded vaccines for special groups – in addition to the routine schedule

Note: Vaccinators are advised to regularly check the Pharmaceutical Schedule and any online updates (www.pharmac.govt.nz) for changes to funding decisions for special groups. See also chapter 4 ‘Immunisation of special groups’.

Vaccine Individuals eligible for funded vaccine
Haemophilus influenzae type b (Hib)
(chapter 6)

For (re-)vaccination of patients who are:

  • post-haematopoietic stem cell transplant (HSCT) or chemotherapy
  • pre- or post-splenectomy or with functional asplenia
  • pre- or post-solid organ transplant
  • pre- or post-cochlear implants
  • undergoing renal dialysis and other severely immunosuppressive regimens

For use in testing for primary immune deficiencya

Hepatitis A
(chapter 7)

Transplant patients

Children with chronic liver disease

Close contacts of hepatitis A cases

Hepatitis B (HepB)
(chapter 8)

Household or sexual contacts of patients with acute or chronic hepatitis B virus (HBV) infection

Babies of mothers with chronic HBV infection need both hepatitis B vaccine (HepB) and hepatitis B immunoglobulin (HBIG) at birth

Children aged under 18 years who have not achieved positive serology and who require additional vaccination

HIV-positive patients

Hepatitis C-positive patients

Following non-consensual sexual intercourse

Patients following immunosuppressionb

Solid organ transplant patients

Post-HSCT patients

Following needle-stick injury

Dialysis patients

Liver or kidney transplant patients

Human papillomavirus (HPV)
(chapter 9)

People aged 9 to 26 years inclusive:

  • with confirmed HIV infection
  • transplant (including stem cell) patients
  • post-chemotherapy
Annual influenza vaccine
(chapter 10)

Patients aged 6 months to <65 years who:

  • have any of the following cardiovascular diseases:
    • ischaemic heart disease
    • congestive heart failure
    • rheumatic heart disease
    • congenital heart disease
    • cerebrovascular disease
  • have either of the following chronic respiratory diseases:
    • asthma, if on a regular preventative therapy
    • other chronic respiratory disease with impaired lung function
  • have diabetes
  • have chronic renal disease
  • have any cancer, excluding basal and squamous skin cancers if not invasive
  • have any of the following other conditions:
    • autoimmune disease
    • immune suppression or immune deficiency
    • HIV
    • transplant recipients
    • neuromuscular and central nervous system diseases/disorders
    • haemoglobinopathies
    • are children on long-term aspirin
    • have a cochlear implant
    • errors of metabolism at risk of major metabolic decompensation
    • pre- and post-splenectomy
    • Down syndrome
  • are pregnant
  • are children aged 4 years and under who have been hospitalised for respiratory illness or have a history of significant respiratory illness
  • are patients who are compulsorily detained long-term in a forensic unit within a DHB hospitalc
Measles, mumps and rubella (MMR)
(chapters 11, 13 and 18)
(Re-)vaccination of patients following immunosuppressionb
Meningococcal C conjugate vaccine (MenCCV) and quadrivalent meningococcal conjugate vaccine (MCV4-D)
(chapter 12)

Pre- and post-splenectomy or with functional or anatomical asplenia

HIV

Complement deficiency (acquired or inherited)

Pre- or post-solid organ transplant

Close contacts of meningococcal cases

HSCT (bone marrow transplant) patients

Following immunosuppressionb

Pertussis-‌containing vaccines
(chapter 14)

Pregnant women between 28 and 38 weeks’ gestation

(Re-)vaccination of patients who are:

  • post-HSCT or chemotherapy
  • pre- or post-splenectomy
  • pre- or post-solid organ transplant
  • undergoing renal dialysis or other severely immunosuppressive regimens
13-valent pneumococcal conjugate vaccine (PCV13) and 23‑valent pneumococcal polysaccharide vaccine (23PPV)
(chapter 15)

1 dose of PCV13 for high-risk children (over the age of 17 months and under 18 years who have received 4 doses of PCV10), and 2 doses of 23PPV for high-risk children aged under 18 years.

PCV13 and 23PPV for (re-)vaccination of high-risk children aged under 5 years:

  • on immunosuppressive therapy or radiation therapy (vaccinate when there is expected to be a sufficient immune response)
  • with primary immune deficiencies
  • with HIV infection
  • with renal failure or nephrotic syndrome
  • who are immune-suppressed following organ transplantation (including HSCT)
  • with cochlear implants or intracranial shunts
  • with cerebrospinal fluid leak
  • who are receiving corticosteroid therapy for more than 2 weeks, and who are on an equivalent daily dosage of prednisone of 2 mg/kg per day or greater, or children who weigh more than 10 kg on a total daily dosage of 20 mg or greater
  • with chronic pulmonary disease (including asthma treated with high-dose corticosteroid therapy)
  • preterm infants, born before 28 weeks’ gestation
  • with cardiac disease, with cyanosis or failure
  • with diabetes
  • with Down syndrome
  • who are pre- or post-splenectomy, or with functional asplenia

PCV13 for 23PPV for (re-)vaccination of patients aged 5 years and older:

  • with HIV
  • pre- or post-HSCTd or chemotherapyd
  • pre- or post-splenectomy or with functional asplenia
  • pre- or post-solid organ transplant
  • undergoing renal dialysis
  • with complement deficiency (acquired or inherited)
  • with cochlear implants
  • with primary immune deficiency

PCV13 and 23PPV for use in testing for primary immune deficiencya

Inactivated polio vaccine (IPV)
(chapter 16)
(Re-)vaccination of patients following immunosuppressionb
Tetanus and diphtheria (Td)
(chapter 19)

(Re-)vaccination of patients following immunosuppressionb

Boosting of patients with tetanus-prone wounds

For use in testing for primary immune deficiencya

Bacillus Calmette–Guérin (BCG)
(chapter 20 and Appendix 8)

For infants at increased risk of tuberculosis (TB):

  • living in a house or family with a person with current or past history of TB; or
  • having one or more household members or carers who within the last 5 years lived in a country with a rate of TB ≥40 per 100,000 for 6 months or longer; or
  • during their first 5 years will be living 3 months or longer in a country with a rate of TB ≥40 per 100,000
Varicella vaccine (VV)
(chapter 21)

Non-immune patients:

  • with chronic liver disease who may in future be candidates for transplantation
  • with deteriorating renal function before transplantation
  • prior to solid organ transplant
  • prior to any elective immunosuppressionb
  • for post-exposure prophylaxis of immune-competent hospital in-patients

Patients at least 2 years after bone marrow transplantation, on advice of their specialist

Patients at least 6 months after completion of chemotherapy, on advice of their specialist

HIV-positive patients with mild or moderate immunosuppression who are non-immune to varicella, on advice of their HIV specialist

Patients with inborn errors of metabolism at risk of major metabolic decompensation, with no clinical history of varicella

Household contacts of paediatric patients who are immunocompromised, or undergoing a procedure leading to immunocompromise, where the household contact has no clinical history of varicella

Household contacts of adult patients who have no clinical history of varicella and who are severely immunocompromised or undergoing a procedure leading to immunocompromise, where the household contact has no clinical history of varicella

  1. Upon the recommendation of an internal medicine physician or paediatrician.
  2. The period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days.
  3. This is a Pharmaceutical Schedule Section H – Hospital Medicines List funding restriction.
  4. PCV13 is funded pre- or post-HSCT or chemotherapy. 23PPV is only funded post-HSCT or chemotherapy.

Eligibility for publicly funded vaccines

Only vaccines given according to the Schedule are available free of charge, unless there is a specific funded programme in response to a recognised need (see Table 2). The immunisation benefit is paid by DHBs to providers for the administration of:

Currently there is no funding provided for the administration of tetanus and diphtheria (Td) boosters given at ages 45 and 65 years, although the vaccine is free.

The Health and Disability Services Eligibility Direction 2011 (the Eligibility Direction) issued by the Minister of Health sets out the eligibility criteria for publicly funded health and disability services in New Zealand. Only people who meet the eligibility criteria defined in the Eligibility Direction can receive publicly funded (ie, free or subsidised) health and disability services.

Regardless of their immigration and citizenship status, all children aged under 18 years are eligible to receive Schedule vaccines, and providers can claim the immunisation benefit for administering the vaccines. All children are also eligible for Well Child Tamariki Ora services.

Non-residents who were aged under 18 years when they commenced HPV vaccination are currently funded to complete the course, even if they are aged 18 years or older when they complete it.

Further information on eligibility can be found on the Ministry of Health website (www.health.govt.nz/eligibility).

Notifiable diseases

All diseases preventable by vaccines on the Schedule (or as part of a targeted programme) are notifiable, except for HPV, seasonal influenza, rotavirus and varicella.

Note: Rotavirus infections presenting as gastroenteritis are notifiable as acute gastroenteritis.

Notification processes, and the diseases to which they relate, have been updated in the Health Act and supporting Health (Infectious and Notifiable Diseases) Regulations 2016. See the Ministry of Health document Guidance on Infectious Disease Management under the Health Act 1956 (available at www.health.govt.nz/publication/guidance-infectious-disease-management-under-health-act-1956) for an explanation, as well as the processes and forms for notifiable diseases.

The case definitions used by the medical officer of health to classify the notified case for surveillance purposes (and to assist in identifying appropriate prevention and control activities) and the laboratory tests required to confirm the diagnosis can be found in the Communicable Disease Control Manual 2012. For the most up-to-date information, refer to the online version (available at www.health.govt.nz/publication/communicable-disease-control-manual-2012).

1 General immunisation principles

In this chapter:

1.1 Immunity and immunisation

1.2 From personal protection to community (herd) immunity

1.3 The importance of immunisation coverage

1.4 Classification of vaccines

1.5 Vaccine ingredients

1.6 Safety monitoring of vaccines in New Zealand

References

1.1 Immunity and immunisation

Immunity is the biological state of being able to resist disease: the primary objective of vaccination is to induce an immunological memory against specific diseases, so that if exposure to a disease-causing pathogen occurs, the immune response will neutralise the infection before disease can occur.

1.1.1 Immune recognition

One of the primary ways in which the immune system achieves elimination of pathogens and other unwanted foreign material is through a ‘self’ tag. Each cell in the body is equipped with a type of molecule that identifies the individual from any other, much like a barcode. Pathogens not only lack a ‘self’ tag, they also contain a range of material termed ‘virulence factors’ that the immune system recognises as danger signals.

Antigens (antibody generators) are the drivers of an immune response. Antigens are usually part of a foreign protein or glycoprotein; molecular shapes that the immune system recognises as foreign and trigger an adaptive immune response. While some vaccines contain the entire weakened or attenuated organism (such as measles, mumps and rubella vaccines), increasingly vaccines now contain purified antigens (as in acellular pertussis, HPV or pneumococcal vaccines).

The first process that occurs when a foreign antigen, such as a vaccine antigen, is introduced to the body is the recognition that the antigen is non-self. The antigen is taken up at the local site (such as the injection site) by professional phagocytic cells called antigen-presenting cells; for example, macrophages and dendritic cells. Once inside the antigen-presenting cells, degradation of the foreign protein (or microbe) occurs and tiny fragments are carried to the cell surface and displayed along with a ‘self’ tag molecule. These antigen-presenting cells then make their way through the lymph to the local lymph node where the adaptive immune response is initiated.

1.1.2 Induction of the adaptive immune response

The adaptive immune response occurs in lymphoid tissue, primarily the lymph nodes, of which there are 500–600 distributed throughout the body, including the spleen.

The adaptive immune response to most vaccines occurs at the draining lymph node proximal to the site of injection. The spleen and lymph nodes are densely populated with important effector lymphocytes of the immune response: the T-cells and B-cells. The lymph that flows through the nodes brings with it the vaccine antigen that has been captured at the injection site by the specialised antigen-presenting cells. Once in the lymph node the vaccine antigen, in combination with the cell that has carried it there, comes into contact with the specific T‑cells and B-cells.

Among the trillions of specific T and B lymphocytes (~1016 possibilities) there (usually) exists a match for the antigen. The process that occurs once these cells recognise each other is the primary immune response and it matures over a period of four to six weeks.

An early outcome of the interaction between these antigen-presenting cells and T and B lymphocytes is the production of antibody-producing B-cells. Antibody can be measured in the blood as soon as 4–7 days, but is usually more effectively measured weeks to months later. Initially, this is low in quantity and of low affinity for the antigen (binds weakly to the antigen), and primarily consists of the antibody subtype immunoglobulin M (IgM), often referred to as ‘early antibody’. It peaks at around 7–10 days then declines relatively quickly (see Figure 1.1).

For most vaccine-preventable diseases this process is too slow following infection, and disease occurs before an effective immune response can be mounted. Injecting a subunit part of the disease in the form of vaccine readies the immune response so an effective immune response can be mounted more rapidly when the wild disease is encountered.

1.1.3 Development of immune memory and the secondary response

Following the primary immune response, a reaction occurs within the lymph node. Over a period of around two months, cells that are less specific for the specific antigen are deleted, and those that are highly specific are retained and divide. During this time immunological memory cells also develop.

The next time the same antigen is introduced, either as a pathogen component or as a further dose of vaccine subunit, the immunological memory cells will recognise it and begin to proliferate. Highly specific antibody (primarily of the IgG subtype, but also IgA) is rapidly produced in large amounts. The lag phase is much shorter than the primary immune response (see Figure 1.1), just 1–4 days; the antibody peaks very quickly and lasts much longer.

The immune system has been readied by the vaccine; if the actual disease pathogen enters the body, then it is recognised by the immune system and is prevented from causing disease.

Figure 1.1: Comparison of primary and secondary immune responses to protein-containing vaccines

Secondary responses are faster (peaking at day 7) than the primary immune response and the antibody titres are higher, more prolonged and of higher neutralising capacity.

Figure 1.1: Comparison of primary and secondary immune responses to protein-containing vaccines
Figure 1.1: Comparison of primary and secondary immune responses to protein-containing vaccines
Innate immunity

Most infectious microbes (also known as micro-organisms) are prevented from entering the body by barriers such as skin, mucosa, cilia and a range of anti-microbial enzymes. Any microbes that breach these surface barriers are then attacked by other components of the innate immune system, such as polymorphonuclear leucocytes (neutrophils), macrophages and complement.

This non-specific immune response termed ‘innate’ is robotic and does not involve learnt or adaptive mechanisms. The cells and proteins of the innate immune system are able to recognise common microbial fragments and can kill microbes without the need for prior exposure. The cells of the innate immune system also interact with the cells of the adaptive immune system (eg, lymphocytes) to induce a cascade of events that results in the development of adaptive immunity and immune memory, as summarised in Figure 1.2.

Figure 1.2: Summary of non-specific innate and adaptive (specific) immunity
Figure 1.2: Summary of non-specific innate and adaptive (specific) immunity

1.1.4 Acquisition of adaptive immunity

Specific antibody can be acquired either naturally via infection or ‘artificially’ using vaccines by teaching the immune system to respond to specific parts of the potential pathogenic antigens. This is termed adaptive or learnt immunity.

Naturally acquired immunity

Naturally acquired immunity occurs either actively by experiencing the infection or passively through the transfer of maternal antibodies from mother to fetus or infant (transplacentally or in breastmilk).

Artificially acquired immunity

‘Artificially’ acquired immunity occurs either actively through vaccination or passively through administration of immunoglobulin (IG) (see Appendix 6).

While actively acquired immunity lasts from years to life, passively acquired immunity lasts from weeks to months as the transferred antibodies decay and are not renewed.

1.1.5 Maternally derived immunity

The passive transfer of antibody from mother to fetus provides an opportunity to provide protection to the neonate against several diseases before they are old enough to be vaccinated themselves. Maternal vaccination boosts the immunity of the mother, inducing high levels of maternal antibody. This antibody is actively transported across the placenta to concentrate at protective levels by birth (in term infants).

Important diseases that maternal vaccination is effective at preventing include neonatal tetanus, influenza and pertussis in the infant for the first weeks or months of life (see section 4.1 and the relevant disease chapters).

1.1.6 Summary

1.2 From personal protection to community (herd) immunity

By protecting individuals, vaccination can also protect the wider community. This herd immunity occurs when the vaccine coverage is high, meaning an infectious case is unlikely to encounter susceptible contacts, so transmission stops.

When a vaccine is able to prevent carriage and transmission of a human-only pathogen such as polio virus, measles virus or Streptococcus pneumoniae, the whole population benefits, and these agents can be reduced and even eliminated. This phenomenon, called herd or community immunity, can prevent infections spreading and therefore protect vulnerable members of the population, such as the very young, very old, or those with underlying conditions that increase their risk from infectious diseases (immunocompromised). These individuals may not themselves be able to receive some vaccines (eg, live vaccines) or may not mount an effective immune response to other vaccines.

The population benefits depend on the disease itself and the nature of the vaccine. A recent example of herd immunity in New Zealand is the significant reduction in rotavirus hospital discharge rates in children aged under 5 years following the July 2014 introduction of rotavirus vaccine for infants (see section 17.3.2).

1.2.1 Reproduction number (R₀) and herd immunity threshold (H)

A measure of the infectiousness of a disease is the basic reproduction number (R₀). This is the number of secondary cases generated by a typical infectious individual when the rest of the population is susceptible. In other words, R₀ describes the spreading potential of an infection in a population.1 Measles is one of the most infectious diseases, with an R₀ of 12–18 (Table 1.1). In other words, one person with measles is likely to infect up to 18 other susceptible people. Pertussis is similarly infectious.

If a significant proportion of the population are immune, then the chain of disease transmission is likely to be disrupted. The herd immunity threshold (H) is the proportion of immune individuals in a population that must be exceeded to prevent disease transmission. For example, to prevent measles or pertussis transmission, 92–94 percent of the population must be immune (Table 1.1).

R₀ must remain above 1 in order for an infection to continue to exist. Once R₀ drops below 1 (such as in the presence of an effective vaccination programme), the disease can be eliminated. The greater the proportion of the population that is immune to the infection, the lower the R₀ will be. For example, data2 indicates that a quadrivalent HPV vaccine programme with 70 percent coverage in young women may lead to the near disappearance of genital warts from the heterosexual population because the R₀ for HPV types 6 and 11 (causing genital warts) falls to below 1 (see ‘Herd immunity’ in section 9.4.2).

Table 1.1: Approximate basic reproduction numbers (in developed countries) and implied crude herd immunity thresholdsa for common vaccine-preventable diseasesb
Infection Basic reproduction number (R₀) Crude herd immunity threshold, H (%)
Diphtheria 6–7 83–85
Influenzac 1.4–4 30–75
Measlesd 12–18 92–94
Mumps 4–7 75–86
Pertussis 5–17 92–94
Polioe 2–20 50–95
Rubella 6–7 83–85
Varicella 8–10 Not defined

Notes

  1. The herd immunity threshold (H) is calculated as 1−1/R₀.
  2. The values given in this table are approximate: they do not properly reflect the range and diversity among populations, nor do they reflect the full immunological complexity underlying the epidemiology and persistence of these infections.
  3. The R₀ of influenza viruses varies among subtypes.
  4. Herd immunity thresholds as low as 55% have been published.
  5. This is complicated by uncertainties over immunity to infection and variation related to hygiene standards.

Adapted from: Fine PEM, Mulholland K. 2013. Community immunity. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders. Table 71.2.

1.2.2 Summary

1.3 The importance of immunisation coverage

High immunisation coverage not only means more individuals are protected but is vital to achieve herd immunity. High coverage reduces the spread of disease to those who have not been vaccinated for medical reasons (eg, children with leukaemia while receiving treatment) or because of age (eg, infants who are too young to respond to some vaccines). High coverage also reduces the spread of disease to those who may not mount an effective immune response to vaccines because of an underlying condition (eg, those on immunosuppressive regimes).

The World Health Organization (WHO) and the New Zealand government target for immunisation coverage is for at least 95 percent of children to be fully vaccinated by age 2 years. The New Zealand target includes a marker for on-time immunisation of 95 percent by age 8 months, as well as at age 2 years. This target is based on the need for:

For the three months ending 31 December 2016, 93.3 percent of New Zealand children were fully immunised by age 8 months and 93.1 percent were fully immunised by age 2 years. Up-to-date national and DHB immunisation coverage data is available on the Ministry of Health website (www.health.govt.nz/national-and-dhb-immunisation-data).

1.4 Classification of vaccines

There are three broad categories of vaccine type: live attenuated (weakened), killed/inactivated, and subunit. Examples of the different types of vaccines are summarised in Table 1.2.

Table 1.2: Classification of vaccines, with examples
Live attenuated Inactivated or whole killed Subunit

Measles

Mumps

Rubella

Varicella

Rotavirus

Tuberculosis (BCG)

Zoster

Poliomyelitis (IPV)

Hepatitis A

Some influenza vaccines

Toxoid:

  • diphtheria
  • tetanus

Polysaccharide:

  • pneumococcal (23-valent)

Conjugate:

  • pneumococcal (10- and 13-valent)
  • Haemophilus influenzae type b
  • meningococcal (monovalent and quadrivalent)

Recombinant:

  • hepatitis B
  • human papillomavirus

Other subunit:

  • pertussis, acellular
  • influenza

Note: Travel vaccines have been omitted from the above table.

1.4.1 Live attenuated vaccines

Live vaccines contain pathogens, usually viruses, which have been weakened (attenuated) so that they are able to replicate enough to induce an immune response but not cause disease. Immunity from live vaccines is usually very long-lived. The live vaccines on the National Immunisation Schedule are MMR, varicella and rotavirus vaccines.

1.4.2 Killed and inactivated vaccines

Killed vaccines contain whole bacteria that have been killed. The whole-cell pertussis vaccine is an example of a killed vaccine. There are no killed vaccines on the Schedule.

Inactivated vaccines contain viruses that have been inactivated in some way, such as splitting, so they are unable to replicate or cause disease. Examples of inactivated vaccines are influenza and polio vaccines.

1.4.3 Subunit vaccines

Subunit vaccines contain microbial fragments or particles that can induce an immune response which protects against disease. These are produced using a range of methods including recombinant engineering, detoxification processes and splitting and purification.

Toxoid vaccines

In some bacterial infections (eg, diphtheria, tetanus), the clinical manifestations of disease are caused not by the bacteria themselves but by the toxins they secrete. Toxoid vaccines are produced by harvesting a toxin and altering it chemically (usually with formaldehyde) to convert the toxin to a toxoid. The toxoid is then purified. Toxoid vaccines induce antibodies that neutralise the harmful exotoxins released from these bacteria.

Recombinant vaccines

Recombinant vaccines, such as those used against HBV and HPV, are made using a gene from the (disease-causing) pathogen. The gene is inserted into a cell system capable of producing large amounts of the protein of interest. The protein produced is capable of generating a protective immune response. For example, the gene for the hepatitis B surface antigen (HBsAg) is inserted into yeast cells, which replicate and produce large amounts of HBsAg. This is purified and used to make vaccine. The advantage of this approach is that it results in a very pure vaccine that is efficient to produce.

Polysaccharide and conjugate vaccines

Polysaccharides are strings of sugars. Some bacteria, such as Streptococcus pneumoniae and Neisseria meningitidis, have large amounts of polysaccharide on their surface, which encapsulate the bacteria. The polysaccharide capsules protect the bacteria from the host’s immune system and can make the bacteria more virulent. Historically, it has been difficult to stimulate an effective immune response to these polysaccharide capsules using vaccines, particularly in children aged under 2 years.

First-generation capsular polysaccharide vaccines contained antigens isolated from the different polysaccharide capsules (eg, 23PPV, see chapter 15). Polysaccharide vaccines are poorly immunogenic, and they only induce a primary immune response. They produce low affinity antibodies (which do not bind well to the antigen) and, because they do not elicit T-cell responses, immune memory is not strong. Multiple priming doses (even a single dose) can cause hyporesponsiveness in both children and adults to further doses. There is also concern that repeated doses could result in ‘clonal deletion’ where the specific B-cell pool becomes depleted due to successive primary responses.

The new generation conjugate vaccines (eg, PCV13 and MCV4-D) contain carrier proteins that are chemically attached to the polysaccharide antigens. Attaching relatively non-immunogenic polysaccharides to the highly immunogenic carrier proteins means that by activating a T-cell response, conjugate vaccines induce both high-affinity antibodies against the polysaccharide antigens, and immune memory.

Examples of carrier proteins and vaccines that use them are:

The new generation conjugate vaccines are limited by the number of polysaccharides that can be covalently linked to the carrier molecule, so there is still a role for polysaccharide vaccines to broaden the number of serotypes recognised. For example, PCV13 has 13 serotypes, compared to 23PPV with 23 serotypes. Conjugate vaccine technology is expected to improve so that polysaccharide vaccines can eventually be phased out.

Principles and implications for using polysaccharide and conjugate vaccines

1.4.4 Summary

1.5 Vaccine ingredients

In addition to the antigen, a vaccine may contain a range of other substances; for example, an immune enhancer (adjuvant) and/or a preservative. Traces of residual components from the manufacturing process may also be present in the vaccine. For further information on vaccine content, see chapter 3 and the vaccine sections within the disease chapters of this Handbook.

1.5.1 Adjuvants

Adjuvants are substances that enhance the immune response to an antigen through a range of mechanisms, including improving the delivery of the antigen to the innate immune system and to the lymphoid organs. Use of adjuvants also means that less antigen (which can be difficult to produce) is needed (antigen sparing).

Adjuvants licensed for human use include aluminium salts (eg, aluminium hydroxide and aluminium phosphate), oil-in-water emulsions (MF59, Novartis; AS03, GSK) and a bacterial endotoxin (AS04, GSK). Most non-live vaccines require an adjuvant, and most vaccines still use aluminium adjuvants. The amount of aluminium contained in a vaccine is very small compared with that present in our daily intake from food and water, including breastmilk.

1.5.2 Preservatives

Preservatives prevent the contamination of vaccines, particularly in multi-dose vials. 2-phenoxyethanol is an example of a preservative used in some vaccines. It is also used in many cosmetics and baby care products. Many vaccines do not contain a preservative. Mercury-based preservatives (thiomersal) are not used in vaccines on the New Zealand National Immunisation Schedule.

1.5.3 Stabilisers

Stabilisers protect the vaccine from adverse conditions (such as exposure to heat), inhibit chemical reactions and prevent components from separating. Examples include sucrose, lactose, albumin, gelatin, glycine and monosodium glutamate (MSG).

1.5.4 Surfactants/emulsifiers

These are wetting agents that alter the surface tension of a liquid, like a detergent does. Surfactants assist particles to remain suspended in liquid, preventing settling and clumping. A commonly used surfactant is polysorbate 80, made from sorbitol (sugar alcohol) and oleic acid (an omega fatty acid). It is also commonly used in foods such as ice-cream.

1.5.5 Residuals

Residuals are traces of substances that remain in the vaccine as an inevitable consequence of the manufacturing process. Regulatory bodies vary as to which trace substances must be specified. Residuals may include virus-inactivating agents (such as formaldehyde), antibiotics and other substances used in the manufacturing process, such as egg protein and gelatin.

1.6 Safety monitoring of vaccines in New Zealand

1.6.1 The approval of vaccines for use in New Zealand

Vaccines, like all medicines, have benefits and risks of harm. Before a medicine or vaccine is approved for use, it must be tested in clinical trials to determine its efficacy and safety profile. Information about efficacy and potential risks of harm is identified from the clinical trial data and assessed before the medicine or vaccine is approved for use.

Known information about each medicine and vaccine is published for health professionals in a manufacturer’s data sheet, available on the Medsafe website (www.medsafe.govt.nz). Consumer medicine information is usually also published.

Once the vaccine is used freely (ie, outside of the clinical trials), further information becomes available on its safety profile. Some adverse reactions are rare and may not be seen until a very large number of people have received the medicine or vaccine. This is one of the reasons why it is important to monitor all medicines and vaccines after they have been approved (registered). Note that some vaccines that are approved for use by Medsafe may not have been made available for distribution by the manufacturer or supplier.

Most countries (including New Zealand) have a safety monitoring system, which includes a voluntary spontaneous reporting scheme, to help identify any possible safety concerns. These reporting systems feed into the WHO Collaborating Centre for International Drug Monitoring, called the Uppsala Monitoring Centre, located in Sweden. This means that international data, often covering millions of doses, is available for Medsafe, which is the medicines regulator responsible for monitoring information to ensure that approved vaccines remain acceptably safe for use in New Zealand. Vaccine safety is never reviewed in isolation from the expected benefits of the vaccine; it is always looked at in terms of the risk–benefit balance.

In addition, the WHO plays an important role in vaccine safety through its Strategic Advisory Group of Experts on Immunization and the Global Advisory Committee on Vaccine Safety.

1.6.2 The New Zealand spontaneous reporting scheme

Two terms are used to describe spontaneous reports. Adverse events are undesirable events experienced by a person, which may or may not be causally associated with the vaccine. Adverse reactions are undesirable effects resulting from medicines or vaccines (ie, they are causally associated).

Spontaneous reports are case reports of adverse events that people have experienced while or after taking a medicine or having a vaccine. Medsafe contracts the collection, review and analysis of this information to the New Zealand Pharmacovigilance Centre at the University of Otago in Dunedin.

Health care professionals and consumers are encouraged to report adverse events following immunisation (AEFIs) to the Centre for Adverse Reactions Monitoring (CARM), which is part of the New Zealand Pharmacovigilance Centre. Pharmaceutical companies also submit adverse event reports.

Further information about suspected adverse reactions (and events following immunisation) reported in New Zealand can be found in the Suspected Medicine Adverse Reaction Search (SMARS) on the Medsafe website (www.medsafe.govt.nz/projects/B1/ADRDisclaimer.asp). See below for details about how to report to CARM and what information should be reported.

1.6.3 AEFI reporting process – notifying CARM

How to report to CARM

Adverse events may be reported to CARM by:

Send reporting forms to:

Freepost 112002
The Medical Assessor
Centre for Adverse Reactions Monitoring (CARM)

University of Otago Medical School
PO Box 913
Dunedin 9710

Telephone:   (03) 479 7247
Fax:                 (03) 479 7150
Email:            carmnz@otago.ac.nz
Website:       www.otago.ac.nz/carm

In terms of guidance, the sort of information the reporting form generally requires is a patient identifier (gender, age, initial), a medicine, a reaction and the reporter’s contact details.

What should be reported?

Health professionals/vaccinators should report:

Individuals or parents/guardians should be encouraged to notify vaccinators of any AEFI that they consider may have been caused by the vaccination. Alternatively, individuals or parents/guardians may wish to notify CARM themselves, or they can contact their general practice or the Immunisation Advisory Centre (IMAC) (0800 IMMUNE /
0800 466 863) to help with notification.

If in doubt, report it.

Table 1.3: Examples of AEFIs to be reported
Timeframe Event
All vaccines
Within 24 hours of vaccination

Anaphylactic reaction (acute hypersensitivity reaction)

Anaphylaxis

Persistent inconsolable screaming (more than 3 hours)

Hypotonic-hyporesponsive episode

Fever >40°C

Within 5 days of vaccination

Severe local reaction

Sepsis

Injection site abscess

Within 12 days of vaccination

Seizures, including febrile seizures

Encephalopathy

Within 3 months of vaccination

Acute flaccid paralysis* (AFP), including Guillain–Barré syndrome (GBS)

Brachial neuritis (usually occurs 2–28 days after tetanus-containing vaccine)

Thrombocytopenia (usually occurs 15–35 days after MMR)

Between 1 and 12 months after BCG vaccination

Lymphadenitis

Disseminated BCG infection

Osteitis/osteomyelitis

No time limit

Intussusception after rotavirus vaccine

Any death, hospitalisation, or other severe or unusual events of clinical concern that are thought by health professionals or the public to possibly be related to vaccination

Newly introduced vaccines, or those with new indications or being delivered by a different route
No time limit All suspected adverse reactions

*     AFP in children is also monitored by the New Zealand Paediatric Surveillance Unit as part of polio eradication surveillance (see chapter 16).

Seriousness of AEFIs

Reports of suspected adverse reactions or AEFIs can be categorised as serious or non-serious. This categorisation system is a tool used to try and prioritise safety concerns. It is not a reflection of the importance of the events to the consumer or their health care professional. Because a report is defined as serious based on what is reported, it is possible to have both serious and non-serious cases reporting the same type of event; for example, headache.

International convention defines the seriousness of reports based on the outcome or nature of the reported event as documented in the report, irrespective of whether there is any association to the medicine or vaccine.

Serious events are based on the following international criteria:

CARM assessment of causality

The WHO recommends that individual reports of adverse reactions to vaccines are assessed for causality. This assessment is a tool used to help detect new safety concerns; it is not a determination of whether a vaccine caused an adverse reaction.

The person reporting the event will receive a letter of response from CARM commenting on the adverse effect, the causal relationship, the number of other similar events, and advice about future use of the vaccine in the individual. Also, where applicable, CARM will provide a validated AEFI code to the NIR.

The information provided by CARM:

1.6.4 What does Medsafe do with this information?

Medsafe and CARM analyse spontaneous reports in conjunction with other information to determine whether there are any new potential safety signals. Medsafe seeks the advice of independent experts through the Medicines Adverse Reactions Committee, or may form working groups of experts to provide advice. Medsafe works closely with other regulatory authorities from around the world.

Medsafe undertakes a risk–benefit assessment of safety signals to decide if action is required. Further information on risk–benefit assessment is provided on the Medsafe website (www.medsafe.govt.nz/Consumers/ Safety-of-Medicines/Medsafe-Evaluation-Process.asp).

Most safety signals are not supported by any additional information, and no action is taken, although Medsafe may continue to monitor the issue closely. A small number of possible safety signals are confirmed as real. In these cases, Medsafe has a number of regulatory actions it can take, including withdrawing the product.

In New Zealand, it is less likely that any new rare side-effects to vaccines will be detected because of the small number of people immunised compared to other countries. Therefore, Medsafe uses international data available from the WHO, other regulators and pharmaceutical companies to help assess any reports of rare events following immunisation and to determine if they may be new events linked to immunisation.

1.6.5 Advantages and limitations of spontaneous reports

Spontaneous reports have been shown to be a very simple way of identifying potential or possible safety signals with medicines, and over 90 countries have a spontaneous reporting system. They can be used to monitor the safety of medicines in real-life use over the lifetime of the medicine, and for all types of people.

The limitations of using spontaneous reports include under-reporting, a lack of reliable information on the extent of use of the medicine, and wide variations in the clinical details provided about the event and the history of the patient. Spontaneous reports are heavily subject to reporting bias, such as media or other attention on an issue. They are also not very effective at detecting adverse reactions that occur a long time after starting the medicine.

For these reasons, such reports are only used to identify safety signals. These signals require further formal epidemiological study before they can be validated or discounted. Information obtained from spontaneous reports needs to be interpreted with caution.

Understanding vaccine safety and spontaneous reporting

Spontaneous report patterns can be variable, and they depend on many factors. Summaries of reported events following immunisation are not lists of known or proven adverse reactions to vaccines. They cannot be used to determine the frequency of adverse reactions to vaccines in the whole population, and they cannot be used to directly compare the relative safety of vaccines. They must not be interpreted and used as such.

Health care professionals and consumers are encouraged to report any suspicions that an event they have experienced may have been caused by vaccination. Therefore, reports sent to CARM may be:

With any vaccine, the adverse events that are generally reported include:

There will always be a number of coincidental events reported because vaccines are given to large sections of the population. In some cases, vaccines are specifically targeted at people with underlying medical conditions (eg, the influenza vaccine). The challenge is to be able to distinguish these coincidental ‘background’ events from those that may have been caused by the vaccine. There are a range of research methods for assessing the risk of an event after a vaccine compared with the risk with no vaccine exposure.

The time between immunisation and an event can be important in determining whether the event was coincidental. Most reactions to vaccines occur within a very short time of immunisation, usually within days.

Another important approach taken when assessing vaccine safety is comparing the number of reports for a specific event with the expected background rate for that event. When doing this, it is important to ensure that definite diagnoses of the events reported were made and to adjust the background rate for any differences in population groups and seasonal variations.3

References

  1. Fine PEM, Mulholland K. 2013. Community immunity. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  2. Read TRH, Hocking JS, Chen MY, et al. 2011. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sexually Transmitted Infections 87(7): 544–7.
  3. Sexton K, McNicholas A, Galloway Y, et al. 2009. Henoch-Schönlein purpura and meningococcal B vaccination. Archives of Disease in Childhood 94(3): 224–6.

2 Processes for safe immunisation

In this chapter:

2.1 Pre-vaccination

2.2 Vaccine administration

2.3 Post-vaccination

References

2.1 Pre-vaccination

The ‘Immunisation standards for vaccinators’ and the ‘Guidelines for organisations storing vaccines and/or offering immunisation services’ apply to the delivery of all Schedule vaccines and those not on the Schedule. See Appendix 3.

The vaccinator is responsible for ensuring all the vaccines they are handling and administering have been stored at the recommended temperature range of +2°C to +8°C at all times (see ‘Cold chain management’ below and the National Standards for Vaccine Storage and Transportation for Immunisation Providers 20171). Information on vaccine presentation, preparation and disposal can be found in Appendix 7.

Vaccinators are expected to know and observe standard occupational health and safety guidelines in order to minimise the risk of spreading infection and needle-stick injury (see Appendix 7).

All vaccinations on the New Zealand National Immunisation Schedule are given parenterally (by injection) except for the rotavirus vaccine which is given non-parenterally (orally). For non-parenteral vaccine administration, follow the manufacturer’s instructions.

2.1.1 Cold chain management

All vaccines must be stored and/or transported within the recommended temperature range of +2°C to +8°C at all times. Refer to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 20171 for detailed vaccine storage, transportation and destruction information.

The ‘cold chain’ is defined as ‘the system of transporting and storing vaccines within the recommended temperature range of +2°C to +8°C from the place of manufacture to the point of vaccine administration (the individual)’. The integrity of the cold chain is dependent not only on the equipment used for storage, transportation and monitoring but also on the people involved and the processes/practices they undertake.

Table 2.1: Key points for cold chain management
All vaccinators are responsible for ensuring the vaccines they administer have been stored correctly.
All immunisation providers storing vaccines must use a pharmaceutical refrigerator.
The pharmaceutical refrigerator minimum and maximum temperatures must be monitored and recorded at the same time on a daily basis.
All immunisation providers must monitor the refrigerator with an electronic temperature recording device (eg, a data logger) that records and downloads data on a weekly basis. This should be compared with the daily minimum/maximum recordings.
All immunisation providers who store vaccines and/or offer immunisation services must achieve Cold Chain Accreditation.
Each immunisation provider must have a written cold chain management policy in place and ensure their policy is reviewed and updated annually. Each vaccinator is responsible to ensure they are able to access this policy, as it will contain important practice information on vaccine storage.
If the vaccine refrigerator temperature goes outside the recommended +2°C to +8°C range
  • Label the vaccines ‘not for use’.

If the refrigerator is currently running within the +2°C to +8°C range, leave the labelled vaccines in your refrigerator.

If the refrigerator is not within the +2°C to +8°C range, pack your labelled vaccines into a chilly bin, with a temperature monitoring device and consider transporting to your back-up provider (details for this are in your cold chain policy).

  • Download the data logger and check for inconsistencies or temperature fluctuations; note any temperature fluctuations outside the +2°C to +8°C range, and the time period.
  • Contact your local immunisation coordinator for advice and further actions.
  • Document the steps and actions you have taken.

2.1.2 Informed consent

What is informed consent?

Informed consent is a fundamental concept in the provision of health care services, including immunisation. It is based on ethical obligations that are supported by legal provisions (eg, the Health and Disability Commissioner Act 1994, Code of Health and Disability Services Consumers’ Rights 1996, Health Information Privacy Code 1994, Privacy Act 1993 and Privacy Amendment Act 2013).

Providing meaningful information to enable an informed choice, and seeking informed consent, is a duty that all health and disability providers must meet to uphold the rights of health and disability consumers. Informed consent includes the right to be honestly and openly informed about one’s personal health matters. The right to agree to treatment carries with it the right to refuse and withdraw from treatment.

Informed consent is also an external expression of a health care provider’s pivotal ethical duty to uphold and enhance their patient’s autonomy by respecting the patient’s personhood in every aspect of their relationship with that individual.

The informed consent process

Informed consent is a process whereby the individual and/or their representative (if the individual does not have the capacity to consent) are appropriately informed in an environment and manner that are meaningful. Then, having been well informed, they are willing and able to agree to what is being suggested without coercion.

Regardless of age, an individual and/or their parent/guardian must be able to understand:

With regard to vaccination, the individual or parent/guardian needs to understand the benefits and risks of vaccination, including those to the child and community, in order to make an informed choice and give informed consent.

The essential elements of the informed consent process are effective communication, full information and freely given competent consent. The specific rights in the Code of Health and Disability Services Consumers’ Rights that represent these three elements are:

For example, section 7(1) of the Code states that ‘services may be provided to a consumer only if that consumer makes an informed choice and gives informed consent, except where any enactment, or the common law, or any other provision of the Code provides otherwise.’ Information on the Code of Health and Disability Services Consumers’ Rights can be found on the Health and Disability Commissioner’s website (www.hdc.org.nz).

Health professionals have legal obligations to obtain informed consent prior to a procedure and prior to data collection (eg, data collected for the NIR). Unless there are specific legal exceptions to the need for consent, the health professional who acts without consent potentially faces the prospect of a civil claim for exemplary damages, criminal prosecution for assault (sections 190 and 196 of the Crimes Act 1961), complaints to the Health and Disability Commissioner, and professional disciplining.

Ensuring that an individual has made an informed choice regarding treatment options has been included in the Health Practitioners Competence Assurance Act 2003. This Act ensures that health practitioners are, and remain, competent and safe to practise. For example, the Nursing Council of New Zealand competencies for the Registered Nurse Scope of Practice, Competency 2.4, ‘ensures the client has adequate explanation of the effects, consequences and alternatives of proposed treatment options’ (see the Nursing Council of New Zealand website, www.nursingcouncil.org.nz).

Privacy, and control over personal information

The right to authorise, or to exert some control over, the collection and disclosure of personal information about oneself is a right closely allied to that of consent to treatment and is also relevant to personal integrity and autonomy. The Health Information Privacy Code 1994 gives people the right to access, and seek correction of, health information about them (Rules 6 and 7). It also requires health agencies collecting identifiable information to be open about how and for what purpose that information will be stored, and who will be able to see it (Rule 3).

Parents and guardians have a similar right of access to information about their children under section 22F of the Health Act 1956. This right is limited in that access requests can be refused if providing the information would be contrary to the interests or wishes of the child.

Further information about privacy and health information can be found on the Privacy Commissioner’s website (www.privacy.org.nz), or by calling the privacy enquiries line: 0800 803 909.

Immunisation consent in primary care

Parents should be prepared during the antenatal period for the choice they will have to make about their child’s vaccination. During the third trimester of pregnancy, the lead maternity carer must provide Ministry of Health information on immunisation and the NIR. This is a requirement under clause DA21(c) of the Primary Maternity Services Notice 2007, pursuant to section 88 of the New Zealand Public Health and Disability Act 2000.

Vaccine hesitancy

Vaccine hesitancy refers to delay in acceptance or refusal of vaccines despite availability of vaccination services. Vaccine hesitancy is complex and context specific varying across time, place and vaccines. It includes factors such as complacency, convenience and confidence.

WHO: Addressing Vaccine Hesitancy (www.who.int/immunization/programmes_systems/vaccine_hesitancy/en/)

Effective communication and active listening are key components of the informed consent process, especially when health care providers are working with vaccine-hesitant individuals/parents/guardians.

Information for parents, guardians and health care providers

Health care providers must offer information without individuals or parents/guardians having to ask for it. The depth of information offered or required may differ, but it should at least ensure that the individual or parent/guardian understands what the vaccine is for and the possible side-effects, as well as information about the vaccination programme, the NIR and the risks of not being vaccinated (see chapter 3).

Every effort should be made to ensure that the need for information is met, including extra discussion time, use of an interpreter and alternative-language pamphlets. (Ministry of Health immunisation pamphlets are produced in several languages, and are available from the local authorised provider or can be ordered, viewed and/or downloaded from the HealthEd website: www.healthed.govt.nz)

Issues to discuss with individuals or parents/guardians about immunisation include:

Informed consent is required for each immunisation episode or dose. Presentation for an immunisation event should not be interpreted as implying consent. Individuals and parents/guardians have the right to change their mind at any time. Where consent is obtained formally but not in writing, the provider should document what was discussed, and that consent was obtained and by whom.

Ministry of Health information

Ministry of Health immunisation information for parents and guardians is available on the Ministry of Health’s website (www.health.govt.nz/immunisation). Parents and guardians may also order, view or download Ministry of Health immunisation information from the HealthEd website (www.healthed.govt.nz) or from the local authorised resource provider, including:

Further immunisation consent information for health care providers is also available in Appendix 3 of this Handbook ‘Immunisation standards for vaccinators and Guidelines for organisations offering immunisation services’. Responses to commonly asked questions and suggestions for addressing myths and concerns are available in chapter 3 of this Handbook ‘Vaccination questions and addressing concerns’.

Other information sources

Alternatively, contact:

Immunisation consent in other settings (eg, schools)

In mass immunisation campaigns, such as those undertaken at schools, the consent requirements are different from those that apply to the vaccination of individuals in primary care. The parent/guardian may not be with the child on the day of immunisation, so immunisation should proceed only after the parent/guardian has had the opportunity to read the immunisation information and discuss any areas of concern. Consent forms are provided for immunisations given in schools by public health nurses. For children aged under 16 years who are being immunised at school, written consent must be obtained from the parent/guardian. Individuals who are aged 16 years or older may self-consent.

Consent and children

Under the Code of Rights, every consumer, including a child, has the right to the information they need to make an informed choice or to give informed consent. The law relating to the ability of children to consent to medical treatment is complex. There is no one particular age at which all children can consent to all health and disability services. The presumption that parental consent is necessary in order to give health care to those aged under 16 years is inconsistent with common law developments and the Code of Rights.

The Code of Rights makes a presumption of competence (to give consent) in relation to children, although New Zealand is unusual in this respect (ie, the obligations regarding consent of minors are greater in New Zealand than in many other jurisdictions).

A child aged under 16 years has the right to give consent for minor treatment, including immunisation, providing he or she understands fully the benefits and risks involved. In 2002 the Health and Disability Commissioner provided an opinion of a child’s consent to a vaccine, whereby the Commissioner was satisfied that a 14-year-old was competent to give informed consent for an immunisation event due to an injury where a tetanus toxoid vaccine would be commonly given. More details of this opinion can be found on the Health and Disability Commissioner’s website (www.hdc.org.nz – Case: 01HDC02915).

Further information on informed consent can be found on the Health and Disability Commissioner’s website (www.hdc.org.nz).

2.1.3 Pre-vaccination screening

Prior to immunisation with any vaccine, the vaccinator should ascertain if the vaccinee (child or adult) has a condition or circumstance which may influence whether a vaccine is given, deferred or contraindicated. Refer to Table 2.2 below, which provides a checklist of conditions or circumstances to screen for, along with the appropriate action to take and a rationale.

The vaccinator will also need to determine which vaccines the vaccinee is due to have, assess the vaccinee’s overall current vaccination status and address parental concerns. The vaccinator also needs to advise the individual/parent/guardian they will need to remain for 20 minutes post-vaccination.

Table 2.2: Pre-vaccination screening and actions to take
Condition* or Circumstance Action Rationale

Is unwell today:

  • fever ≥38°C
  • acute systemic illness

Defer all vaccines until afebrile.

Note: Children with minor illnesses (without acute symptoms/signs) should be vaccinated.

To avoid an adverse event in an already unwell child, or to avoid attributing symptoms to vaccination.
Is a preterm infant and had apnoeas following immunisation in hospital (6-week and/or 3-month event) Re-admission for the next infant immunisation and respiratory monitoring for 48 to 72 hours may be warranted,3 but do not avoid or delay immunisation. There is a potential risk of apnoea in infants born before 28 weeks’ gestation.
Previously had a severe reaction to any vaccine Careful consideration will be needed depending on the nature of the reaction. If in doubt about the safety of future doses, seek specialist advice. Anaphylaxis to a previous vaccine dose or any component of the vaccine is an absolute contraindication to further vaccination with that vaccine.
Anaphylaxis to vaccine components (eg, gelatin, egg protein, neomycin)

Refer to the relevant vaccine data sheet (www.medsafe.govt.nz) for the components.

If an individual has had anaphylaxis to any component contained in a vaccine, seek specialist advice.

Egg allergy, including anaphylactic egg allergy, is not a contraindication to MMR vaccination.

However, a history of egg anaphylaxis warrants the first dose of influenza vaccine to be given in a supervised medical setting4 (see section 10.6.2).

Vaccinators need to be aware of the possibility that allergic reactions, including anaphylaxis, may occur after any vaccination without any apparent risk factors (see section 2.3.3).

Delayed hypersensitivity to a prior vaccine dose or a component of a vaccine is not a contraindication to further doses, but it is important to distinguish these from anaphylaxis.

Appropriate spacing between doses of the same vaccine (when was the last vaccination, and what was it?)

See section 2.1.5 and check the relevant disease chapters and catch-up schedules.

(See below for live parenteral vaccines.)

The general rule is for a minimum of 4 weeks between doses of a primary series and 4 months between the priming dose(s) and the booster.
Had a live parenteral vaccine within the last 4 weeks – if in doubt, check the individual’s immunisation status on the NIR (if applicable) Delay live attenuated parenteral vaccines to 4 weeks.

The antibody response to the first dose may interfere with the response to the second. They may be given on the same day without interference.

Note that this does not apply to rotavirus vaccine, which is a non-parenteral vaccine.

Had an injection of immunoglobulin or a blood transfusion within the last 11 months and is now due for a live vaccine

Check which product the person received and the interval since administration, and refer to Table A6.1.

Delay vaccination if necessary.

Live virus vaccines should be given at least 3 weeks before, or deferred for up to 11 months after, doses of human normal immunoglobulin or other blood products. The interval will be determined by the blood product and dose received.
Has a disease that lowers immunity, is receiving treatment that lowers immunity or is an infant of a mother who received immunosuppressive therapy during pregnancy

See chapter 4 ‘Immunisation of special groups’.

In some cases, specialist advice may need to be sought before vaccination.

Note: Persons living with someone with lowered immunity should be vaccinated, including with live viral vaccines (see section 4.3.1).

The safety and effectiveness of the vaccine may be suboptimal in persons who are immunocompromised.

Live attenuated vaccines may be contraindicated.

Is planning a pregnancy

See section 4.1.1 ‘For women planning pregnancy’.

Ensure women and household members have received all vaccines recommended for their age group.

Women should know if they are immune to rubella (section 18.5.3) and varicella (section 21.5.4).

Advise women not to become pregnant within 4 weeks of receiving live viral vaccines.

Vaccinating before pregnancy may prevent maternal illness, which could affect the infant, and may confer passive immunity to the newborn.
Is pregnant

See sections 4.1.2 ‘During pregnancy’ and 4.1.3 ‘Breastfeeding and post-partum’.

Influenza and Tdap vaccines are recommended.

Vaccinating (with inactivated vaccines) during pregnancy may prevent maternal illness, which could affect the infant, and may confer passive immunity to the newborn.
Live vaccines should be avoided until after the delivery. Deferring administration of live vaccines until after delivery is a precautionary safety measure. Studies of women who inadvertently received a live vaccine during pregnancy and their infants have not identified any adverse effects.
Undiagnosed or evolving neurological condition (for pertussis-containing vaccines only) Seek specialist advice. There is the potential for confusion about the role of vaccination in the context of a clinically unstable illness. The risks and benefits of withholding vaccination until the clinical situation has stabilised should be considered on an individual basis.
Thrombocytopenia or bleeding disorders

Administer intramuscular vaccines with caution:

  • use a 23-gauge or smaller needle and apply firm pressure to the injection site (without rubbing) for at least 10 minutes.
A haematoma may occur following intramuscular administration. The subcutaneous route is still recommended by some authorities – seek specialist advice when appropriate.

*     See chapter 4 ‘Immunisation of special groups’ for more information about pregnancy and lactation and for information about infants with special immunisation considerations, immune-deficient and immunosuppressed individuals, immigrants and refugees, travel, and occupational and other risk factors.

Adapted from: Department of Health and Ageing. 2016. The Australian Immunisation Handbook (10th edition; updated August 2016). Canberra, ACT: Department of Health and Ageing. Table 2.1.2.

2.1.4 Contraindications

No individual should be denied vaccination without serious consideration of the consequences, both for the individual and for the community. Where there is any doubt, seek advice from the individual’s general practitioner (GP), a public health medicine specialist, medical officer of health, consultant paediatrician or IMAC.

Live viral vaccines should not be given to pregnant women, nor, in general, to immunosuppressed individuals (see chapter 4).

See the relevant disease chapter section for more specific vaccine contraindications.

Conditions that are not contraindications to immunisation

The conditions in Table 2.3 are not contraindications to the immunisation of children and adults (see also section 3.1).

Table 2.3: Conditions that are not contraindications to immunisation

Individuals with these conditions should be vaccinated with all the recommended vaccines.

Mildly unwell, with a temperature less than 38°C
Asthma, hay fever, eczema, ‘snuffles’, allergy to house dust
Treatment with antibiotics or locally acting steroids
A breastfeeding mother or a breastfed child
Neonatal jaundice
Low weight in an otherwise healthy child
The child being over the usual age for immunisation – use age-appropriate vaccines, as per the catch-up schedules in Appendix 2 (the exception is rotavirus vaccine, see section 17.5.2)
A previous hypotonic-hyporesponsive episode (see section 2.3.3)
Clinical history of pertussis, measles, mumps or rubella infection – clinical history without laboratory confirmation cannot be taken as proof of immunity (even when an individual is proven to be immune to one or two of either measles, mumps or rubella, there is still the need for immunisation against the other/s, see the relevant chapters)
Prematurity, but an otherwise well infant – it is particularly important to immunise these children, who are likely to suffer severe illness if infected; immunisation is recommended at the usual chronological age (see ‘Preterm and low birthweight infants’ in section 4.2.1)
Stable neurological conditions, such as cerebral palsy or Down syndrome
Contact with an infectious disease
Egg allergy, including anaphylaxis, is not a contraindication to MMR vaccine (see section 11.6.3) or influenza vaccine (see section 10.6.2)
Family history of vaccine reactions
Family history of seizures
Family history of sudden unexpected death in infancy (SUDI)
Child’s mother or household member is pregnant or immunocompromised

2.1.5 Spacing of doses

In general, follow the recommendations in the manufacturers’ data sheets.

Principles for spacing of doses of the same vaccine

The immune response to a series of vaccines depends on the time interval between doses. The general rule is for a minimum of four weeks between doses of a primary series; however, the immune response may be better with longer intervals. A repeat dose of the same vaccine given less than four weeks after the previous dose may result in a reduced immune response. Specific recommendations for a rapid schedule by the manufacturer may apply for some vaccines.

Generally, a minimum interval of four to six months between priming dose(s) and the booster dose allows affinity maturation of memory B cells, and thus higher secondary responses (see section 1.1).

It is not necessary to repeat a prior dose if the time elapsed between doses is more than the recommended interval.

Spacing of different vaccines

Two or more parenterally administered live vaccines may be given at the same visit; for example, MMR and VV. However, when given at different visits, a minimum interval of four weeks is recommended. This interval is to avoid the response to the second vaccine being diminished due to interference from the response to the first vaccine. Note that no interval is required between administration of bacillus Calmette–Guérin (BCG) and rotavirus vaccines.

Unless there is a specific recommendation against it, an inactivated or subunit vaccine can be administered either simultaneously or at any time before or after a different inactivated, subunit or live vaccine.

Concurrent administration of vaccines

Best practice is to follow the Schedule. Changing the timing of visits or increasing the number of visits to avoid multiple injections delays protection against potentially serious diseases and may also lead to incomplete immunisation.

2.1.6 Catch-up programmes for unimmunised or partially immunised children

The objective of a catch-up programme is to complete a course of vaccinations that provides adequate protection. Catch-up programmes should be based on documented evidence of previous vaccination (eg, the child’s Well Child Tamariki Ora My Health Book, NIR or overseas immunisation records).

When children have missed vaccine doses, it is important to bring them up to date as quickly as possible. Where more than one vaccine is overdue, it is preferable to give as many as possible at the first visit. For children aged 15 months and older, MMR is the priority.

If the vaccinator is uncertain about how to plan a catch-up programme, they should contact the local immunisation coordinator, IMAC, medical officer of health or public health service.

Once catch-up is achieved, the child should continue as per the Schedule.

Vaccination of children with inadequate vaccination records

Children without a documented history of vaccination are recommended to have a full course of vaccinations appropriate for their age. In cases of doubt, it is safe to repeat vaccine doses: it is preferable for the individual to receive an unnecessary dose than to miss out a required dose(s) and not be fully protected.

2.1.7 Adult vaccination (aged 18 years and older)

Whenever adults are seen in general practice or by immunisation providers, there is an opportunity to ensure they have been adequately protected against the following diseases and have received at least a primary immunisation course as described in Table 2.4. If the requisite number of doses has not been received, catch-up vaccination is recommended and funded (see Appendix 2).

Women of childbearing age should know whether or not they are immune to rubella (see chapter 18) and varicella (see chapter 21).

Table 2.4: Primary immunisation requirements for adults (funded)
Disease Number of vaccine doses
Tetanus 3 doses
Diphtheria 3 doses
Poliomyelitis 3 doses
Measles, mumps, rubella 2 doses
HPV (aged 26 years and under) 3 doses*

*     Individuals who were under age 27 years when they commenced HPV vaccination are currently funded to complete the 3-dose course, even if they are older than 27 years when they complete it.

See Table 2.5 for adult vaccination recommendations, including vaccinations recommended for at-risk groups (funded vaccines are in the shaded boxes). See also chapter 4 ‘Immunisation of special groups’ for information about immunisation during pregnancy and lactation (section 4.1), of immunocompromised individuals (section 4.3), of immigrants and refugees (section 4.4), for travel (section 4.5), and for those with occupational and other risk factors (section 4.6).

Table 2.5: Adult (≥18 years) vaccination recommendations, excluding travel requirements
Vaccine Recommended and funded Recommended but not funded
Hib
(chapters 4 and 6)
(Re-)vaccination of patients post-haematopoietic stem cell transplant (HSCT) or chemotherapy; pre- or post-splenectomy or with functional asplenia; pre- or post-solid organ transplant, pre- or post-cochlear implants, renal dialysis and other severely immunosuppressive regimens  
Hepatitis A
(chapter 7)

Transplant patients

Close contacts of hepatitis A casesa

Patients with chronic hepatitis B or C infection; men who have sex with men; adults at occupational risk
Hepatitis B
(chapter 8)

Household or sexual contacts of patients with acute or chronic HBV infection

HIV-positive patients

Hepatitis C-positive patients

Following non-consensual sexual intercourse

Following immunosuppressionb

Solid organ transplant patients

Post-HSCT patients

Following needle-stick injury

Dialysis patients

Liver or kidney transplant patients

Non-immune adults at risk including occupational or other risk factors
HPV
(chapter 9)

Individuals aged 18–26 yearsc,d

Individuals aged 18–26 years:c,d

  • with confirmed HIV infection
  • transplant (including stem cell) patients
  • an additional dose post-chemotherapy

Adults ≥27 years:c,d,e

  • who have had little previous exposure to HPV and are now likely to be exposed
  • who are men who have sex with men
  • with HIV
Annual influenza vaccine
(chapter 10)

Pregnant women

Individuals aged 65 years and older

Individuals aged under 65 years with eligible conditions

All other adults
MMR
(chapters 11, 13 and 18)

Any individual susceptible to any one of these three diseases

(Re-)vaccination following immunosuppressionb

 
MenCCV and MCV4‑D
(chapters 4 and 12)

For patients who are pre- or post-splenectomy or with functional asplenia; with HIV; with complement deficiency (acquired, including monoclonal antibody therapy against C5, or inherited); who are pre- or post-solid organ transplant

Close contacts of meningococcal casesa

HSCT (bone marrow transplant) patients

Patients following immunosuppressionb

Young adults in communal accommodation

Laboratory personnel routinely exposed to N. meningitidis

Pertussis-containing vaccine (chapters 4 and 14)

Tdap for pregnant women from 28 to 38 weeks’ gestation of every pregnancy

Tdap for (re-)vaccination of patients who are post-HSCT or chemotherapy; pre- or post-splenectomy; pre- or post-solid organ transplant, renal dialysis and other severely immunosuppressive regimens

Tdap instead of Td if likely to be in contact with infants aged under 12 months
PCV13 and 23PPV
(chapters 4 and 15)
(Re-)vaccination of patients with HIV; pre- or post-HSCTf or chemotherapy;f pre- or post-splenectomy or with functional asplenia; pre- or post-solid organ transplant; renal dialysis; complement deficiency (acquired or inherited); cochlear implants; primary immune deficiency

PCV13 followed by 23PPV for those with certain conditions

PCV13 followed by 23PPV for those aged 65 years or older

IPV
(chapter 16)

Any unvaccinated or partially vaccinated individual

(Re-)vaccination following immunosuppressionb

 
Td
(chapters 5 and 19)
Td for susceptible individuals (including following immunosuppression); boostersg at 45 and 65 years; boosting of patients with tetanus-prone wounds Tdap instead of Td if likely to be in contact with infants aged under 12 months
Varicella
(chapter 21)

Non-immune patients:

  • with chronic liver disease who may need a transplant in the future
  • with deteriorating renal function before transplantation
  • prior to solid organ transplant
  • prior to any elective immunosuppressionb
  • for post-exposure prophylaxis of immune-competent hospital in-patients

Patients at least 2 years after bone marrow transplanth

Patients at least 6 months after completion of chemotherapyh

HIV-positive patients who are non-immune to varicella, with mild or moderate immunosuppressionh

Patients with inborn errors of metabolism at risk of major metabolic decompensation, with no clinical history of varicella

Household contacts of paediatric patients who are immunocompromised or undergoing a procedure leading to immunocompromise, where the household contact has no clinical history of varicella

Household contacts of adult patients who have no clinical history of varicella and who are severely immunocompromised or undergoing a procedure leading to immunocompromise, where the household contact has no clinical history of varicella

Susceptible adults
  1. Only 1 dose of vaccine is funded for close contacts.
  2. Note that the period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days.
  3. Individuals who started with HPV4 may complete their remaining doses with HPV9.
  4. Individuals who were <27 years when they commenced HPV vaccination are currently funded to complete the 3-dose course, even if they are ≥27 years when they complete it.
  5. HPV9 vaccine is registered for use in females aged 9–45 years and in males aged
    9–26 years. However, there are no theoretical concerns that the efficacy or safety of HPV vaccine in males up to the age of 45 years will differ significantly from females of the same age or younger males.
  6. PCV13 is funded pre- or post-HSCT or chemotherapy. 23PPV is only funded post-HSCT or chemotherapy.
  7. The administration charge for the Td booster is not funded, although the vaccine is free.
  8. On the advice of their specialist.

2.2 Vaccine administration

2.2.1 Minimising pain and distress at the time of vaccination

The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) key recommendations for minimising pain and distress at the time of vaccination are:5

See also section 2.3.2 and the IMAC factsheet Mitigating Vaccination Pain and Distress (available at www.immune.org.nz/resources/written-resources).

2.2.2 Preparing for vaccine administration

Correct vaccine administration is important, and vaccinators have a responsibility to see that vaccines are given:

The use of alternative sites will be based on professional judgement, including knowledge of the potential risks at each site and recommendations in the manufacturer’s data sheet.

The guidelines below will help to make the experience less distressing for the individual, parent/guardian and/or whānau, and vaccinator.

Table 2.6: Guidelines for vaccine administration
Preparation Immunisation event
Vaccinate in a private and appropriate setting. Draw up injections out of sight, if possible. Medical paraphernalia is commonplace to vaccinators, but it may heighten the anxiety of some individuals.
Prepare the area/room layout to suit the vaccinator and vaccination event. Ensure the individual or parent/guardian has had the opportunity to discuss any concerns and has given informed consent.
Be familiar with the vaccines (eg, their correct preparation, administration and the potential for adverse events). Be prepared to include other family members and whānau in the discussion, and explain to older children accompanying infants why the injections are being given and what will happen.
Be aware of the individual’s immunisation history (eg, submit an NIR status query if the history is unknown). Give the appropriate immunisations due and advise when the next immunisation event is due.
Ensure there are age-appropriate distractions available.

For babies, suggest that the mother breastfeeds baby before, during and after immunisation.

For children, sit them upright and talk quietly to the child before and during immunisation. Make eye contact and explain what is going to happen. Even when a child is unable to understand the words, an unhurried, quiet approach has a calming effect and reassures the parent/guardian.

See also section 2.3.2.

Ensure the relevant immunisation health education resources are available. Give written and verbal advice to the individual and parent/guardian. The advice should cover what may be expected after immunisation, and what to do in the event of an adverse event, along with advice on when to notify the vaccinator.
Removal of air bubbles

Advice for removal of air in the syringe before vaccine administration is dependent on the vaccine presentation. See Table 2.7.

Table 2.7: Guidelines for management of air bubbles in a vaccine syringe
Vaccine presentation Management of air bubbles
Vaccines supplied in a prefilled syringe with a fixed needle (eg, Influvac) Do not expel the air
Vaccines supplied in a prefilled syringe without a fixed needle (eg, Gardasil 9)

Add an appropriate administration needle

Do not expel the air

Vaccines supplied diluted in a vial (eg, HBvaxPRO)

Draw up the entire vaccine volume into a syringe

Expel the air until the vaccine is at the level of the syringe hub, then change the needle

Do not expel the air contained in the new needle

Vaccines supplied as diluent and powder/pellet requiring reconstitution (eg, Infanrix-hexa, Priorix)

Reconstitute the vaccine correctly

Draw up the entire vaccine volume into a syringe

Expel the air until the vaccine is at the level of the syringe hub, then change the needle

Do not expel the air contained in the new needle

Skin preparation

Skin preparation or cleansing when the injection site is clean is not necessary. However, if an alcohol swab is used, it must be allowed to dry for at least two minutes, otherwise alcohol may be tracked into the muscle, causing local irritation. Alcohol may also inactivate a live attenuated vaccine such as MMR.

A dirty injection site may be washed with soap and water and thoroughly dried before the immunisation event.

2.2.3 Route of administration

Needle angle, gauge and length

Where possible, vaccinators should refer to the vaccine data sheet (available on the Medsafe website: www.medsafe.govt.nz) for the route of administration.

Most Schedule vaccines (with the exception of MMR, VV and IPV, which are administered subcutaneously, and rotavirus, which is administered orally) are administered by intramuscular injection. Intramuscular injections should be administered at a 90 degree angle to the skin plane. The needle length used will be determined by the size of the limb and muscle bulk, whether the tissue is bunched or stretched, and the vaccinator’s professional judgement. BCG vaccine (which can only be administered by authorised vaccinators with BCG endorsement) is given by intradermal injection. See Table 2.8.

Table 2.8: Needle gauge and length, by site and age
Age Site Needle gauge and length Rationale
Intramuscular (IM) injection
Birth Vastus lateralis 23–25 G × 16 mm  
6 weeks Vastus lateralis 23–25 G × 16 or 25 mm Choice of needle length will be based on the vaccinator’s professional judgement.
3–14 months Vastus lateralis 23–25 G × 25 mm A 25 mm needle will ensure deep IM vaccine deposition.
15 months to
3 years
Deltoid or 23–25 G × 16 mm The vastus lateralis site remains an option in young children when the deltoid muscle bulk is small and multiple injections are necessary.
Vastus lateralis 23–25 G × 25 mm
3–7 years Deltoid 23–25 G × 16 mm A 16 mm needle should be sufficient to effect deep IM deposition in the deltoid in most children.
Vastus lateralisa 21–22 G × 25 mm  
Older children (7 years and older), adolescents and adults Deltoidb 23–25 G × 16 mm, or
23–25 G × 25 mm, or
21–22 G × 38 mm
Most adolescents and adults will require a 25 mm needle to effect deep IM deposition.
Vastus lateralisa 21–22 G × 38 mm  
Subcutaneous injection
Subcutaneous injection Deltoid region of the upper arm 25–26 G × 16 mm An insertion angle of 45 degrees is recommended. The needle should never be longer than 16 mm or inadvertent IM administration could result.
Intradermal injection: BCG vaccine – for authorised vaccinators with BCG endorsement
Intradermal injection Slightly above the insertion of the deltoid muscle on the lateral surface of the left arm. The arm should be gently but firmly supported. Drawing-up: Tuberculin syringe (attach a drawing-up needle), or a single-use insulin syringe with a needle attached  
Administering: If using a tuberculin syringe, change the needle to a sterile 26 G × 13 or 16 mm needle (no needle change required if using an insulin syringe) The syringe should be held with the bevel uppermost, parallel with the skin of the arm. The bevel should be fully inserted but visible under the skin. Inject the vaccine slowly and gradually to form a white ‘bleb’ or wheal, then gradually withdraw the needle.
  1. Consideration may be given to the vastus lateralis as an alternative vaccination site, providing it is not contraindicated by the manufacturer’s data sheet.
  2. For females weighing <60 kg use a 23–25 G × 16 mm needle; for 60–90 kg use a
    23–25 G × 25 mm needle; for >90 kg use a 21–22 G × 38 mm needle. For adolescent and adult males, a 23–25 G × 25 mm needle is sufficient.6, 7
Intramuscular injection sites

Injectable vaccines should be administered in healthy, well-developed muscle, in a site as free as possible from the risk of local, neural, vascular and tissue injury. Incorrectly administered vaccines (incorrect sites and poor administration techniques) contribute to vaccine failure, injection site nodules or sterile abscesses, and increased local reactions.

The recommended sites for intramuscular (IM) vaccines (based on proven uptake and safety data) are:

The deltoid muscle is not routinely used in infants and young children aged under 15 months, due to the potential for deltoid or radial nerve injury. However, when there is no access to the vastus lateralis (eg, the infant is in a spica cast), the deltoid muscle is used to administer intramuscular vaccines.

The buttock should not be used for the administration of vaccines in infants or young children, because the buttock region is mostly subcutaneous fat until the child has been walking for at least 9 to 12 months. Use of the buttock is not recommended for adult vaccinations either, because the buttock subcutaneous layer can vary from 1 to 9 cm and IM deposition may not occur.

With older children and adults, consideration may be given to using the vastus lateralis as an alternative site to the deltoid, providing it is not contraindicated by the manufacturer’s data sheet.

Subcutaneous injection sites

A subcutaneous (SC) injection should be given into healthy tissue that is away from bony prominences and free of large blood vessels or nerves. The recommended site for subcutaneous vaccine administration is the upper arm (overlying the deltoid muscle).

The principles for locating the upper arm site for an SC injection are the same as for an IM injection. However, needle length is more critical than angle of insertion for subcutaneous injections. An insertion angle of 45 degrees is recommended and the needle should never be longer than 16 mm, or inadvertent IM administration could result. The thigh may be used for SC vaccines unless contraindicated by the manufacturer’s data sheet. See also Table 2.2 for information about thrombocytopenia and bleeding disorders.

Intradermal injections

The intradermal injection technique for BCG vaccine (see section 2.2.4) requires special training, and should only be performed by an authorised vaccinator with BCG endorsement (see Appendix 4).

Oral vaccine administration

The rotavirus vaccine is administered orally. Administer the entire contents of the oral applicator into the infant’s mouth, towards the inner cheek (see section A7.2.4). Do not inject oral vaccines.

For specific oral vaccine administration instructions, refer to the vaccine data sheet (available on the Medsafe website: www.medsafe.govt.nz).

2.2.4 Infant vaccination

Infants aged under 6 months do not need to be grasped or restrained as firmly as toddlers or older children. At this age, excessive restraint increases their fear as well as muscle tautness. The recommended positioning for an infant is in a cuddle hold with parent/guardian, breastfeeding as appropriate. The cuddle position offers better psychological support and comfort for both the infant and the parent/guardian,5 and the parent/guardian should be offered this position as a first choice (Figure 2.1).

If the parent/guardian is helping to hold the infant or child, ensure they understand what is expected of them and what will take place. Most vaccinators choose to administer all the injections due quickly and soothe the infant or child afterwards (see section 2.3.2 for soothing measures).

Figure 2.1: The cuddle position for infants
Figure 2.1: The cuddle position for infants
Vastus lateralis

To locate the injection site, undo the nappy, gently adduct the flexed knee and (see Figure 2.2):

  1. find the greater trochanter
  2. find the lateral femoral condyle
  3. section the thigh into thirds and run an imaginary line from the centre of the lower marker to the centre of the upper marker (look for the dimple along the lower portion of the fascia lata).

The injection site is at the junction of the upper and middle thirds and slightly anterior to (above) the imaginary line, in the bulkiest part of the muscle.

Figure 2.2: Photo showing the infant lateral thigh injection site
Figure 2.2: Photo showing the infant lateral thigh injection site

The needle should be directed at a 90 degree angle to the skin surface and inserted at the junction of the upper and middle thirds. Inject the vaccine at a controlled rate. To avoid tracking, make sure all the vaccine has been injected before smoothly withdrawing the needle. Do not massage or rub the injection site afterwards. However, infants with a bleeding disorder may require firm pressure over the injection site without rubbing for at least 10 minutes.

BCG vaccine (administered by authorised vaccinators with BCG endorsement)

The reconstituted BCG vaccine is given by intradermal injection slightly above the insertion of the deltoid muscle on the lateral surface of the left arm. The infant’s arm should be gently but firmly supported (see Figure 2.3[a]). The syringe should be held with the bevel uppermost, parallel with the skin of the arm (see Figure 2.3[b]).

Figure 2.3: Photos showing the infant BCG vaccination site, and how to support the infant’s arm and hold the syringe
DSC02779
(a)
DSC02782
(b)

Inject the vaccine slowly (see Figure 2.4[a]), then gradually withdraw the needle. The injection is given slowly to avoid leakage around the needle or vaccine being squirted. Safety glasses should be used to protect the eyes of those involved. If BCG vaccine is accidentally squirted into the eyes, wash them immediately with water. Following BCG vaccination a white weal should appear (see Figure 2.4[b]), which should subside in approximately 30 minutes. The vaccination site requires no swabbing or dressing.

Figure 2.4: Photos showing the BCG vaccine being slowly injected, and a white weal appearing as the needle is gradually withdrawn
DSC02780
(a)
DSC02783
(b)

2.2.5 Young child vaccination (vastus lateralis or deltoid)

The choice between the two sites for IM injections from 15 months of age will be based on the vaccinator’s professional judgement, such as knowledge of the child and ease of restraint. Some vaccinators consider the vastus lateralis preferable for young children when the deltoid muscle bulk is small and because of the superficiality of the radial nerve. Discuss the options with the parent/guardian when making your decision. (See also ‘The 15-month event’ in section 2.2.7.)

The easiest and safest way to position and restrain a young child for a lateral thigh and/or deltoid injection is to sit the child sideways on their parent’s or guardian’s lap. The parent’s/guardian’s hand restrains the child’s outer arm and the child’s legs are either restrained between the parent’s/guardian’s legs or by placing a hand on the child’s outer knee or lower leg. Alternatively, the child may face their parent/guardian while straddling the parent’s/guardian’s legs (see Figures 2.5 and 2.6).

Figure 2.5: Photos showing cuddle positions for vastus lateralis or deltoid injections in children
Fig 2
(a)

(b)
Figure 2.6: Photo showing the straddle position for vastus lateralis or deltoid injections in children
Fig 2

If using the straddle position, both the deltoid and vastus lateralis muscle are likely to be more tense or taut, and the injection may therefore be more painful.

2.2.6 Older child, adolescent and adult vaccination (deltoid)

The deltoid muscle is located in the lateral aspect of the upper arm. The entire deltoid muscle must be exposed to avoid the risk of radial nerve injury (an injection at the junction of the middle and upper thirds of the lateral aspect of the upper arm may damage the nerve) (see Figure 2.7).

Figure 2.7: Surface landmarks and structures potentially damaged by intramuscular injection in the upper limb
Figure 2.7: Surface landmarks and structures potentially damaged by intramuscular injection in the upper limb

Reproduced with permission: Cook IF. 2011. An evidence based protocol for the prevention of upper arm injury related to vaccine administration (UAIRVA). Human Vaccines 7(8): 845–8.

The volume injected into the deltoid should not exceed 0.5 mL in children and 1.0 mL in adults.

The vaccinee should be seated with their arm removed from the garment sleeve and hanging relaxed at their side. The vaccinator places their index finger on the vaccinee’s acromion process (the highest point on the shoulder) and their thumb on the vaccinee’s deltoid tuberosity (the lower deltoid attachment point).8

The injection site is at the axilla line, between these anatomical landmarks. The vaccine should be deposited at the bulkiest part of the muscle (Figure 2.8).

Figure 2.8: How to locate the deltoid site
Figure 2.8: How to locate the deltoid site

2.2.7 Multiple injections at the same visit

When more than one vaccine is scheduled at the same visit, vaccinators are recommended to give all of the scheduled vaccines at that visit. This particularly applies to the 15-month event (see below), when four vaccines are scheduled.

Multiple vaccines should not be mixed in a single syringe unless specifically licensed and labelled for administration in one syringe. A different needle and syringe should be used for each injection.

The 15-month event

MMR, varicella, PCV and Hib vaccines are scheduled at the 15-month event. When giving these vaccines, it is preferable to give the live vaccines (MMR and VV) in separate limbs. The IM injections should be given in the vastus lateralis and the SC injections in the deltoid.

The recommended vaccine administration sequence and location is:

  1. Hib: Left vastus (IM)
  2. Varicella: Left deltoid (SC)
  3. PCV: Right vastus (IM)
  4. MMR: Right deltoid (SC).

If parents/guardians request to split the vaccines given at the 15-month event, then providers are advised to give MMR and VV at the first visit, followed by PCV and Hib at the second visit.

Note:

See also the IMAC video ‘Four in a row – a best practice guide for multiple vaccinations’ (https://vimeo.com/195383691).

Multiple injections in the same muscle

When giving two injections to be given in the same limb, the vastus lateralis is preferred because of its greater muscle mass (see Figure 2.9). The injection sites should be on the long axis of the thigh and separated by at least 2 cm so that localised reactions will not overlap.

If multiple injections in the deltoid are required, the sites should be separated by at least 2 cm.9

Figure 2.9: Diagram showing suggested sites for multiple injections in the lateral thigh
Figure 2.9: Diagram showing suggested sites for multiple injections in the lateral thigh

2.3 Post-vaccination

2.3.1 Post-vaccination advice

Post-vaccination advice should be given both verbally and in writing. The advice should cover:

Table 2.9: Expected vaccine responses
Vaccine Expected vaccine responses
DTaP- or Tdap‑containing vaccine

Localised pain, redness and swelling at injection site

Mild fever

Being grizzly and unsettled

Loss of appetite, vomiting, and/or diarrhoea

Drowsiness

Extensive limb swelling after the 4th or 5th dose of a DTaP‑containing vaccine

Hib

Localised pain, redness and swelling at the injection site

Mild fever

Being grizzly and unsettled

Hepatitis B

Very occasionally pain and redness at the injection site

Nausea or diarrhoea

HPV

Fainting, especially adolescents – this is an injection reaction, not a reaction to the vaccine

Localised discomfort, pain, redness and swelling at the injection site

Mild fever

Headache

Influenza

Localised pain, redness and swelling at injection site

Headache

Fever

MMR

Measles component: Fever which lasts 1–2 days; rash (not infectious) 6–12 days after immunisation

Mumps component: Parotid and/or submaxillary swelling 10–14 days after immunisation

Rubella component: Mild rash, fever, lymphadenopathy, joint pain 1–3 weeks after immunisation

Pneumococcal

Localised pain, redness and swelling at injection site

Mild fever

Irritability, sleep changes

Loss of appetite

Rotavirus

Diarrhoea and or vomiting may occur after the first dose

Mild abdominal pain

Adult Td Localised discomfort, redness and swelling at the injection site
Varicella

Localised pain, redness and swelling at injection site

Mild fever

Mild rash, possibly at the injection site (2–5 lesions, appearing 5–26 days after immunisation)

2.3.2 Recommendations for fever and pain management

The use of paracetamol or ibuprofen around the time of immunisation in anticipation of immunisation-related fever or localised pain occurring is not recommended. However, use of these medicines is recommended if the child is distressed due to fever or pain following immunisation.

Paracetamol use may lower the immune response to some vaccines.10 However, there is no evidence that this results in less protection against disease.

Health care providers are encouraged to discuss with parents possible immunisation responses and non-pharmaceutical management of fever or pain, as well as the role of medicines.

Fever

General fever-relieving measures include:

While a high fever alone does not need treatment, antipyretic analgesics (paracetamol or ibuprofen) may be used for distress or pain in a febrile child who has not responded to the cooling measures described above.

Pain management and soothing measures

For infants aged under 12 months, breastfeeding before, during and after the injection can provide comfort and pain relief.5, 11

Give the rotavirus vaccine 1–2 minutes before the other immunisations; rotavirus vaccines contain sucrose that has been shown to reduce pain.511 The infant can then be breastfed (where possible) or held comfortably while the other immunisations are given.

For infants aged under 6 months the 5 S’s (swaddling, side/stomach position, shushing, swinging and sucking) have been found to be effective for soothing and reducing pain after immunisations.12

Using age-appropriate distraction has been shown to reduce pain and distress.5, 11 Examples include showing an interesting or musical toy to an infant, or encouraging an older child to blow using a windmill toy or bubbles. Electronic games/phone games can be useful for older children and teenagers. Do not rub the injection site after the injection as it increases the risk of vaccine reactogenicity.

For infants and children, the use of a topical anaesthetic cream or patch has been found to be effective for immunisation pain management.5, 11 Parents/guardians and those administering the vaccine should check the manufacturers’ recommendations before using topical anaesthetics. The correct dose for infants needs to be followed particularly carefully due to risk of methaemoglobinaemia. Topical anaesthetics may have a role in managing immunisation pain and anxiety, particularly for children who have had previous multiple medical interventions or needle phobias.

Following immunisation, if an infant or child is distressed by pain or swelling at the injection site, placing a cold, wet cloth on the area may help relieve the discomfort. Antipyretic analgesics (paracetamol or ibuprofen) may be used if the above measure does not relieve the child’s distress.

2.3.3 Anaphylaxis and emergency management

Anaphylaxis is a very rare, unexpected and potentially fatal allergic reaction. It develops over several minutes and usually involves multiple body systems. Unconsciousness is rarely the sole manifestation and only occurs as a late event in severe cases. A strong central pulse (eg, carotid) is maintained during a faint (vasovagal syncope), but not in anaphylaxis.

In general, the more severe the reaction, the more rapid the onset. Most life-threatening adverse events begin within 10 minutes of vaccination. The intensity usually peaks at around one hour after onset. Symptoms limited to only one system can occur, leading to delay in diagnosis. Biphasic reactions, where symptoms recur 8 to 12 hours after onset of the original attack, and prolonged attacks lasting up to 48 hours have been described. All patients with anaphylaxis should be hospitalised.

Signs of anaphylaxis

Anaphylaxis is a severe adverse event of rapid onset, characterised by circulatory collapse. In its less severe (and more common) form, the early signs are generalised erythema and urticaria with upper and/or lower respiratory tract obstruction. In more severe cases, limpness, pallor, loss of consciousness and hypotension become evident, in addition to the early signs. Vaccinators should be able to recognise all of the signs and symptoms of anaphylaxis given in Table 2.10.

Table 2.10: Signs and symptoms of anaphylaxis
  Signs and symptoms Severity
Early warning signs (within a few minutes) Dizziness, perineal burning, warmth, pruritus, flushing, urticaria, nasal congestion, sneezing, lacrimation, angioedema Mild to moderate
Hoarseness, nausea, vomiting, substernal pressure Moderate to severe
Laryngeal oedema, dyspnoea, abdominal pain Moderate to severe
Life-threatening symptoms (from soon after the injection up to 20 minutes after) Bronchospasm, stridor, collapse, hypotension, dysrrhythmias Severe

There is no place for conservative management of anaphylaxis. Early administration of adrenaline is essential (for more details, see Table 2.12).

Misdiagnosis of faints and other common causes of collapse as anaphylaxis may lead to inappropriate use of adrenaline. Misdiagnosis as a faint could also lead to a delay in the administration of adrenaline.

Vaccinators should therefore be able to distinguish anaphylaxis from fainting (vasovagal syncope), anxiety and breath-holding spells (see Table 2.11). Infants and babies rarely faint. Sudden loss of consciousness, limpness, pallor and vomiting (signs of severe anaphylaxis in children) should be presumed to be an anaphylactic reaction.

In adults and older children, the most common adverse event is a syncopal episode (fainting), either immediately or soon after vaccination. During fainting the individual suddenly becomes pale, loses consciousness and if sitting or standing will slump to the ground. Recovery of consciousness occurs within a minute or two. Fainting is sometimes accompanied by brief clonic seizure activity, but this generally requires no specific treatment or investigation if it is a single isolated event.

Table 2.11: Distinguishing anaphylaxis from a faint (vasovagal reaction)
  Faint Anaphylaxis
Onset Usually before, at the time, or soon after the injection Soon after the injection, but there may be a delay of up to 30 minutes
System    
Skin Pale, sweaty, cold and clammy Red, raised and itchy rash; swollen eyes and face; generalised rash
Respiratory Normal to deep breaths Noisy breathing due to airways obstruction (wheeze or stridor); respiratory arrest
Cardiovascular Bradycardia; transient hypotension Tachycardia; hypotension; dysrrhythmias; circulatory arrest
Gastrointestinal Nausea/vomiting Abdominal cramps
Neurological Transient loss of consciousness; good response once supine/flat Loss of consciousness; little response once supine/flat
Distinguishing a hypotonic-hyporesponsive episode from anaphylaxis

A hypotonic-hyporesponsive episode is a shock-like state defined by the sudden onset of limpness (muscle hypotonia) and decreased responsiveness with pallor or cyanosis in infants and children aged under 2 years after immunisation.

A hypotonic-hyporesponsive episode can occur from immediately to 48 hours after immunisation, typically lasts less than 30 minutes, and resolves spontaneously.13

A hypotonic-hyporesponsive episode is a recognised serious reaction to immunisation and should be reported to CARM (see section 1.6.3).

Avoidance of anaphylaxis

Before immunisation:

Emergency equipment

Vaccinators, providers and quality managers are responsible for:

Remember, events happen without warning. Appropriate emergency equipment must be immediately at hand whenever immunisations are given, and all vaccinators must be familiar with the practical steps necessary to save lives following an anaphylactic reaction (see Tables 2.12 and 2.13).

Table 2.12: Emergency equipment

An emergency kit should contain:

  • adrenaline* 1:1,000 (3 ampoules) and dosage chart
  • syringes: 1.0 mL (a minimum of 3) (tuberculin not insulin, as the insulin needle is too short for IM injection)
  • needles: a range of needle lengths and gauges, including 23 or 25 G × 25 mm, 22 G × 38 mm
  • a range of airways, including paediatric sizes if vaccinating children.

Other emergency equipment required

It is also necessary to have on hand:

  • an oxygen cylinder (check that it is filled)
  • adult and paediatric bag valve mask resuscitator (eg, Ambu bag), oxygen tubing and a range of oxygen masks
  • access to a telephone.

*     The expiry date of the adrenaline and other medicines should be written on the outside of the emergency kit, and the kit should be checked every 4 weeks. Adrenaline is heat and light sensitive and should be stored appropriately. Adrenaline that has a brown tinge must be discarded.

The emergency kit may need to have additional equipment for non-clinical settings (see Appendix 4).

Hydrocortisone injection is used only under the direction of a medical practitioner (available on Medical Practitioner Supply Order).

Emergency management

An IM injection of 1:1,000 adrenaline is the mainstay of the treatment of anaphylaxis, and adrenaline should be universally available when vaccinating. A tuberculin syringe should be used to ensure the accuracy of measurement when drawing up small doses.

In an emergency situation there is no absolute contraindication to the use of adrenaline. It is, however, a very potent agent, and if used when anaphylaxis has not occurred or in excessive doses, adrenaline can cause dysrrhythmias, severe hypertension and left ventricular failure. Tissue necrosis can occur if the same injection site is used repeatedly.

Intravenous adrenaline should be administered by a medical practitioner with extreme caution, in small boluses, and under careful monitoring, and it is not appropriate as the first line of treatment of anaphylaxis.

Table 2.13: Initial anaphylaxis response/management
CALL FOR HELP – send for professional assistance (ambulance, doctor). Never leave the individual alone.

ASSESS – Assess responsiveness, and check Airway, Breathing, Circulation.

  • If they are conscious, lie the individual down in the recovery position.
  • If they are unconscious and breathing normally, lie the individual down in the recovery position, ensuring that the airway is open.
  • If they are unconscious and not breathing normally, institute standard procedures for basic life support. If cardiorespiratory arrest occurs, administer age-appropriate CPR and life-support measures.

ADMINISTER ADRENALINE by deep intramuscular injection – dosage: 1:1,000 (adrenaline 1:1,000 = 1 mg/mL).

Adrenaline dosage for 1:1,000 formulation is 0.01 mL/kg up to a maximum of 0.5 mL.

If the individual’s weight is unknown, use the following guidelines:
Infant aged under 1 year: 0.05–0.1 mL
Child aged under 2 years: 0.1 mL
Child 2–4 years: 0.2 mL
Child 5–10 years: 0.3 mL
Adolescent ≥11 years: 0.3–0.5 mL
Adult: 0.5 mL
Route: deep IM. Where possible, administer in a non-injected limb, in either the deltoid or vastus lateralis.
You can expect to see some response to the adrenaline within 1–2 minutes. If necessary, adrenaline can be repeated at 5–15-minute intervals, to a maximum of 3 doses, while waiting for assistance. Use alternate sites/limbs for additional doses.
ADMINISTER OXYGEN at high flow rates where there is respiratory distress, stridor or wheeze.
IF HYPOTENSIVE, ELEVATE LEGS.
IF STRIDOR IS PRESENT, ELEVATE HEAD AND CHEST.
RECORD VITAL SIGNS every 5–10 minutes. All observations and interventions need to be clearly documented in medical notes and should accompany the individual to hospital.
ADMIT TO HOSPITAL – all cases of anaphylaxis should be admitted to hospital for observation. Rebound anaphylaxis can occur 12–24 hours after the initial episode.

Note: Only medical practitioners should administer IV adrenaline.

Ongoing management in hospital or by a medical practitioner

Individuals who experience vaccine-related anaphylaxis should be admitted to hospital. If in an unstable or deteriorating condition, and not being transported by ambulance, the individual must be accompanied by the attending health professional so that treatment can be continued during transfer.

Hydrocortisone may be used as adjunctive medication. Nebulised salbutamol is helpful for bronchospasm. For further information, refer to the product data sheet.

Additional drugs that may be administered under the direction of a medical practitioner include:

Observation for a period of up to 24 hours after stabilisation of the individual’s condition is recommended due to the risk of late deterioration from delayed and biphasic reactions.

All anaphylaxis reactions should be reported to CARM (see section 1.6.3).

2.3.4 Documentation and insurance

Accurate documentation, including information on the NIR, School-Based Vaccination System (SBVS) and practice management system, (PMS) is essential. If the vaccinator has not kept accurate clinical records, it is difficult to prove what action/care was or was not taken/delivered if the patient notes are subject to legal scrutiny.

In addition to the information recorded on the NIR (see section 2.3.5), SBVS or PMS, information that should be collected in the patient’s clinical notes includes:

The vaccinator should also complete the relevant sections in the Well Child Tamariki Ora My Health Book and, where applicable, the child’s immunisation certificate (see Appendix 5), the Ministry of Health payment claim form (where applicable), and an NIR notification form if not using a computerised PMS.

Indemnity insurance

All vaccinators should carry indemnity insurance. Most employers have indemnity cover, but vaccinators do not have an automatic right to claim under that cover. Indemnity insurance should cover vaccinators/health professionals for disciplinary proceedings, coroners’ inquiries, and claims of negligence or error that may lead to injury, death or damage.

2.3.5 The National Immunisation Register

The National Immunisation Register (NIR) is a computerised information system that has been collecting immunisation information on New Zealand children since 2005 and from 2014 has been collecting some adult immunisation information. The purpose of the NIR is to facilitate immunisation delivery and provide an accurate record of an individual’s immunisation history.

The NIR also:

Managing the information on the National Immunisation Register

The information held on the NIR (collection, holding, use and disclosure) is governed by the Health Information Privacy Code 1994 and section 22F of the Health Act 1956 (see section 2.1.2).

The NIR’s privacy policy can be found on the Ministry of Health website (www.health.govt.nz/nir). The policy sets out the framework for data collection, storage, use and disclosure of health information held about identifiable individuals on the NIR.

Individuals or their parents/guardians may choose at any time not to have any health information collected on the register (ie, they can opt off the further collection of immunisation data). However, the NIR will retain the individual’s National Health Index (NHI) number, date of birth, DHB they are resident in, date of opt off, and any immunisation information recorded before opt off. The reason for retaining this information is to provide an accurate denominator for immunisation coverage calculations, and to prevent inappropriate recall and referral.

An individual’s immunisation information will be retained on the NIR for their whole life, plus a period of 10 years after their death.

Only authorised users have access to the information held on the NIR. Such a person is authorised to use and disclose NIR information in accordance with their function. Penalties for unauthorised disclosure of information could include the revocation of authorised user privileges, complaints to the Privacy Commissioner, civil proceedings, professional sanctions, and disciplinary action, up to and including termination of employment.

Information collected on the NIR includes:

More information about privacy and informed consent can be found in section 2.1.2 and Appendix 3. Further information about the NIR can be found on the Ministry of Health website (www.health.govt.nz/nir).

The SBVS

The SBVS collects and manages the data for school immunisation programmes (eg, where public health nurses deliver the school year 7 and year 8 immunisation programmes). The information collected on the SBVS for the school immunisation programmes is then transferred to the NIR.

Not all DHBs use the SBVS software for managing their school-based programmes; however, all DHBs are required to record school-based vaccination events on the NIR regardless of whether they use the SBVS, another PMS or direct enter on to the NIR.

References

  1. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  2. Health and Disability Commissioner. Code of Health and Disability Services Consumers Rights. URL: http://www.hdc.org.nz/media/123229/english.pdf (accessed 28 July 2016).
  3. Lee J, Robinson JL, Spady DW. 2006. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatrics 20(6): 20. DOI: 10.1186/1471-2431-6-20 (accessed 11 October 2013).
  4. Centers for Disease Control and Prevention. 2016. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2016–17 influenza season. Morbidity and Mortality Weekly Report: Recommendations and Reports 65(RR05): URL: https://www.cdc.gov/mmwr/volumes/65/rr/rr6505a1.htm (accessed 12 September 2016).
  5. World Health Organization. 2015. Report to SAGE on Reducing Pain and Distress at the Time of Vaccination. URL: http://www.who.int/immunization/sage/meetings/2015/april/1_SAGE_latest_pain_guidelines_March_24_Final.pdf?ua=1 (accessed 27 January 2017).
  6. Poland GA, Borrud A, Jacobsen RM, et al. 1997. Determination of deltoid fat pad thickness: implications for needle length in adult immunization. Journal of the American Medical Association 277(21): 1709–11.
  7. Koster MP, Stellato N, Kohn N, et al. 2009. Needle length for immunization of early adolescents as determined by ultrasound. Pediatrics 124(2): 667–72.
  8. Cook IF. 2011. An evidence based protocol for the prevention of upper arm injury related to vaccine administration (UAIRVA). Human Vaccines 7(8): 845–8.
  9. Centers for Disease Control and Prevention. 2012. Appendix D: Vaccine administration. In: Atkinson W, Hamborsky J, Wolfe S, et al (eds). Epidemiology and Prevention of Vaccine-preventable Diseases (12th edition). Washington, DC: Public Health Foundation.
  10. Prymula R, Siegrest CA, Chlibek R, et al. 2009. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. The Lancet 374(9698): 1339–50.
  11. Taddio A, McMurtry CM, Shah V, et al. 2015. Reducing pain during injections: clinical practice guideline. Canadian Medical Association Journal 187(13): 975–82. DOI: 10.1503/cmaj.150391 (accessed 27 January 2017).
  12. Harrington JW, Logan S, Harwell C, et al. 2012. Effective analgesia using physical interventions for infant immunizations. Pediatrics 129(5):
    815–22. DOI: 10.1542/peds.2011-1607 (accessed 5 November 2013).
  13. Department of Health and Ageing. 2016. Post-vaccination. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part2~handbook10-2-3 (accessed 27 January 2017).

3 Vaccination questions and addressing concerns

In this chapter:

3.1 Some commonly asked questions

3.2 Addressing myths and concerns about immunisation

3.3 Addressing immunisation issues in a constantly changing environment

References

3.1 Some commonly asked questions

3.1.1 Vaccine scheduling

Which vaccines can be administered at the same visit?

There are no known contraindications to administering registered vaccines at the same visit, provided they are administered in separate syringes at separate sites. If two or more parenterally or intranasally administered live vaccines are not given at the same visit, then a minimum interval of four weeks is recommended. The rationale is based on limited data where VV has been given within four weeks of measles-containing vaccine and breakthrough varicella disease (chickenpox) has occurred. Any time interval is acceptable between administering live oral vaccines and all parenteral vaccines (eg, rotavirus and BCG vaccines), live and inactive vaccines, or two inactive vaccines.

What steps are required if the Schedule is interrupted or varied?

Generally, there is no need to repeat prior doses; simply continue the Schedule as if no interruption has occurred (see Appendix 2). Special circumstances where the above does not apply are as follows:

Remember that children who miss one vaccine dose may do so again, so optimising a catch-up schedule is important.

How should the rest of the Schedule be handled when an adverse event has occurred following immunisation?

Proceeding with the Schedule after an AEFI depends on the nature of the event and the likelihood that the vaccine caused it. Most prior adverse events are not contraindications to receiving further immunisations. The only absolute contraindication to receiving a vaccine is an anaphylactic reaction to a prior dose or an ingredient in the vaccine. However, immune dysfunction can be a contraindication to receiving live vaccines (see section 4.3).

Adverse events should be reported to CARM (https://nzphvc.otago.ac.nz/reporting). See section 1.6.3 ‘AEFI reporting process – notifying CARM’.

Consult the AEFI section in each of the Handbook chapters, and seek specialist advice (eg, from the medical officer of health, the Ministry of Health, or IMAC, if required). Other vaccines not related to the AEFI can usually be administered as per the Schedule.

3.1.2 Babies and children

What if a baby had a difficult birth or was premature?

Low birthweight and prematurity are not contraindications to vaccination. The recommended Schedule immunisations should be carried out at the appropriate chronological age. However, if the baby is still in hospital or recently discharged, please seek the advice of the treating specialist (see also section 4.2 on special risk groups and section 8.5.1 on hepatitis B). These babies may be at higher risk of some of these diseases, so vaccinating them on time is particularly important.

Rotavirus vaccine should be given on time to any infant admitted to a general hospital ward (where other patients are not high risk). If standard infection control precautions are maintained, the risk of transmission of vaccine strain rotavirus will be minimal when rotavirus vaccine is administered to hospitalised infants, including hospitalised preterm infants and those in neonatal units.1 (See also section 4.2.1 and chapter 17.)

What special vaccines are offered to newborn babies?

Babies born to HBsAg-positive mothers should receive:

If HBIG and/or HepB is inadvertently omitted, administer as soon as the omission is recognised. HBIG can be administered up to seven days post-delivery. If there is a delay for longer than seven days, seek specialist advice. These babies should then continue as per the Schedule at ages 6 weeks, 3 months and 5 months. Serological testing is required at 9 months of age (see section 8.5.2).

A baby at higher risk of TB is offered a BCG immunisation soon after birth (see section 20.5 for neonatal BCG eligibility and the timing of neonatal BCG). The lead maternity carer will discuss the need for the vaccine with the mother prior to her baby’s birth, and the BCG immunisation may be given while the baby is in hospital, or later at a community clinic.

What are the special requirements of immigrant children?

Immigrant children should be immunised according to the New Zealand Schedule with due account taken of documented prior vaccine administration and the eligibility criteria defined in the Health and Disability Services Eligibility Direction 2011, available on the Ministry of Health website (www.health.govt.nz/eligibility) (see also section 4.4).

It is important to err on the side of giving rather than withholding vaccines if the vaccination history is uncertain (see Appendix 2). The immunisation status of all immigrant children should be checked when they register with a primary health care provider.

Is it possible to boost a child’s immune system by other means?

Eating a healthy diet, getting adequate sleep and exercise, having a smokefree environment and minimising high levels of stress will help keep the immune system healthy. However, none of the above confers the disease-specific immunity that vaccination provides (see also section 3.2.4). All children get infections (eg, common colds) but this does not mean the immune system is not working.

3.1.3 Allergies and illnesses

What if the child is unwell on the day of immunisation?

Minor illness or being in the recovery phase of an illness is not a reason to postpone immunisation. Babies and children with a significant acute illness and a temperature >38°C should have immunisation postponed until they are better. This is not because they are at particular risk of vaccine reactions, but because complications of the acute illness may be misinterpreted as a complication of the immunisation, or an AEFI may complicate the clinical picture of the acute illness. (See ‘Contraindications’ in section 2.1.4, and the contraindications sections in the disease chapters.) If immunisation is postponed, it is important to ensure the child is placed on the recall for the immunisation at a later date.

What if the child is due to have an operation (elective surgery)?

There is no evidence that anaesthetic impairs the immune response to a vaccine or increases the risk of AEFI.

Vaccination with inactive vaccines is preferably avoided for 48 hours prior to an anaesthetic in case post-vaccination symptoms such as fever interfere with preparation for surgery; similarly, live vaccines may induce fever 6–12 days after vaccination. There is no reason to delay surgery following vaccination with a live vaccine if the child is well at the time of immediate pre-operative assessment. There is no reason to delay vaccination after surgery, once the child is well and has recovered from the procedure. See the Association of Paediatric Anaesthetists of Great Britain and Ireland Immunisation guideline (www.apagbi.org.uk/publications/apa-guidelines).

Ideally, individuals scheduled for splenectomy should be immunised at least two weeks before the operation. Pneumococcal, meningococcal, Hib, influenza and varicella vaccines are recommended for these individuals pre- or post-splenectomy (see section 4.3.4 and the relevant disease chapters). Note: If the surgery is an emergency, then the immunisation programme should commence two weeks later.

What if the child has a chronic disease?

Children with chronic diseases should be immunised in the normal way, especially as they may be more at risk from the severe effects of vaccine-preventable diseases. However, if the illness or its treatment results in impaired immunity, immunisation with live vaccines should be considered carefully (see sections 4.2 and 4.3), and the child’s GP or paediatrician should be consulted before immunisation.

What if the child has had seizures?

A diagnosed neurological condition is not a contraindication to any vaccine on the Schedule. However, an evolving neurological condition (eg, uncontrolled epilepsy or a deteriorating neurological state) is still considered a contraindication to pertussis immunisation. Until the neurological condition has been diagnosed or stabilised, there is a risk that changes may be attributed to the vaccine. A family history of seizures or epilepsy of any type is not a contraindication to immunisation.

A febrile reaction may occur after any vaccine and result in a febrile seizure in a susceptible child. Vaccine-related febrile seizures are rare, although the risk is higher following administration of certain vaccines, such as influenza (section 10.7), MMR, and measles, mumps, rubella and varicella (MMRV) (see section 21.7) vaccines. These seizures, although frightening for a parent, are almost always benign, with no associated sequelae.

What if the child is allergic?

Only anaphylaxis to a prior dose of vaccine, or to an ingredient in the vaccine, is considered an absolute contraindication. See the contraindications and precautions section in each disease chapter; in particular, pertussis (section 14.6), measles (section 11.6), influenza (section 10.6) and rotavirus (section 17.6). Children with asthma, eczema, hay fever and other allergies should be immunised in the usual way. Studies have shown that immunised children have slightly lower rates of atopic diseases.2

Can children be immunised if they are known to develop a rash with antibiotics?

Yes – but check the vaccine data sheet for the list of components; some vaccines may contain traces of antibiotics.

The only concern is if a child has had a previous anaphylactic reaction (a rash alone is not anaphylaxis) to a component of a vaccine.

Can all children receive all the vaccines?

A child cannot receive a vaccine if they have had an anaphylactic reaction to any component of the vaccine. A child may have an underlying condition that is a contraindication to some vaccines; for example, children with illnesses or treatments that cause immunocompromise may be unable to receive live attenuated vaccines (see sections 4.2 and 4.3 for special risk groups, chapters 11, 13 and 18 for MMR and chapter 21 for varicella).

3.1.4 Parents, guardians and contacts

What if the child’s mother or guardian is pregnant or breastfeeding?

This is not a contraindication to giving any of the Schedule vaccines to a child, including live vaccines, such as the MMR vaccine. In addition, consideration should be given to the risks for the mother or guardian and baby from diseases such as pertussis, which can be life-threatening in infants.

Pregnancy is an important opportunity to ensure the infant’s siblings have received age-appropriate immunisation.

Pertussis (as Tdap) and influenza vaccines are recommended and funded for pregnant women (see section 4.1).

Are live virus vaccines such as measles, mumps, rubella and varicella transmissible?

These are highly attenuated (weakened) viruses designed specifically to induce an immune response without causing disease. There have been no recorded cases of measles, mumps or rubella disease in individuals who were in contact with a vaccinee. Vaccine-strain varicella transmission to contacts is rare (documented in only 9 immunised people, resulting in 11 secondary cases), and the documented risk of transmission exists only if the immunised person develops a rash3 (see chapters 11, 13 and 18 for MMR and chapter 21 for varicella).

3.2 Addressing myths and concerns about immunisation

Myths about immunisation have existed since the first use of smallpox vaccine over 200 years ago and have resulted in the loss of confidence in immunisation programmes. Misconceptions about vaccines contribute to vaccine hesitancy, which is an issue of global concern. This section provides information to assist providers with addressing concerns about immunisation.

3.2.1 Background

Concerns about immunisation should be taken seriously and responded to appropriately, with as much information as possible. Individuals have the right to make informed decisions for themselves and those in their care, and to accept responsibility for their decisions. It is important to respect this right.

Globally, including in New Zealand, there are many groups of people and individuals who actively campaign against immunisation. Their reasons for doing so may include personal experience, such as an adverse event they have attributed to immunisation, philosophical beliefs, conspiratorial beliefs or dissatisfaction with inadequate or superficial responses from health professionals, who can seem at times to be dismissive of people’s concerns. It is important for all health professionals to be able to provide accurate information about the benefits and risks of immunisation and to respond with as much information as possible to parent/guardian concerns, or refer people appropriately.

It is not always possible to change people’s position by way of scientific argument or presentation of evidence. Anti-immunisation arguments are almost exclusively based on fallacies of fact or logic, or on historical information that is no longer applicable in the current context. Often these arguments can be challenging for the health professional, particularly if they are unfamiliar with the particular argument and when they are complicated by logical flaws.

In any discussion, it may help to acknowledge that science does not always have all the answers, but that it provides a tool with which to answer questions and evaluate the evidence. It is important to point out that an event that follows immunisation is not necessarily caused by the immunisation. Finally, it is always helpful to inform parents/guardians about additional sources of information (see section 2.1.2 on informed consent and section 1.6 on the safety monitoring of vaccines in New Zealand).

3.2.2 Understanding anti-immunisation

People tend to take on board information that supports their belief system and to ignore information that does not. The internet makes it very easy to access material that is appealing. Most people usually make logical decisions based on their perception of risk. Therefore, if a person has the perception that the risk of disease is real and that vaccines are reasonably safe and work, then they are more likely to vaccinate. People are unlikely to vaccinate if they perceive that there is little risk of disease and that vaccines are not safe and do not work.4

3.2.3 Addressing concerns

If a parent is concerned about immunising their child, determining their concerns and addressing them can be helpful. Most often these concerns are around vaccine safety. As a health professional, you should challenge poor information, in a respectful way.

There are three steps you can take when addressing a parent’s or a vaccinee’s concerns.5

1. Understand the specific concerns.

Not every parent or vaccinee has the same concerns, so it is important to first establish what they are worried about. Ask them. It may be helpful to get them to describe what they know about disease risk and vaccine benefit. If they have misconceptions, you can correct them. Evidence has demonstrated that it can be helpful to relay stories of children harmed by vaccine-preventable diseases. Using a vignette can be powerful. If you have no experience of a particular vaccine-preventable disease, see the IMAC website (www.immune.org.nz), or websites such as the Centers for Disease Control and Prevention, the Immunization Action Coalition and the National Centre for Immunisation Research and Surveillance (see Appendix 9).

2. Stay on message.

Keep your messages clear and focussed on the concern at hand.

3. Discuss the rigours of global vaccine research, such as safety systems.

Many vaccine safety myths focus on the limitations of passive reporting systems for adverse events, such as CARM. The many active safety systems and hypothesis-driven research are overlooked. You can highlight that when studies compare the risk for an adverse event in vaccinated children with the risk in unvaccinated children, they support the safety of vaccines.

3.2.4 Debunking a myth

Debunking myths can be very challenging and can also backfire. When you are addressing a myth, there are three important points to remember.6

1. Try not to repeat the myth. Focus on the core facts.

This is because people cannot remember if what they hear was a myth or a fact later on. Debunking can serve to strengthen the myth in people’s minds as either familiar or a threat to their world view. Begin with the core facts.

2. Precede a myth with a warning.

Let them know that ‘this is untrue’, because you often cannot avoid mentioning the myth.

3. Include an alternative explanation that accounts for how the myth misleads.

Do not leave a void but rather replace the myth with accurate information. You can highlight the problems with cherry picking, conspiracy theories and fake experts. If you have them, graphics can be extremely helpful, such as pictures of vaccine-preventable diseases or even a graph showing the impact of vaccination – if you feel it appropriate.

Facts and myths about immunisation

Core fact: Measles and rubella have been eliminated in some countries. The WHO has set targets for global eradication.

Myth: MMR vaccine causes autism.

Explanation: There is no evidence that the MMR vaccine causes autism.7, 8

In 1998 a British physician announced he had found an association between the receipt of MMR vaccine and the development of a new disorder that included autism in a study of 12 children. No subsequent studies following his study have been able to reproduce his results.

In 2004 The Lancet retracted the original 1998 study from the scientific literature on the grounds that it was the product of dishonest and irresponsible research and the British authorities revoked the doctor’s licence to practise medicine.9 In 2008 a press investigation revealed that the doctor had falsified patient data and relied on laboratory reports that he had been warned were incorrect. Studies exonerating the MMR vaccine continue to be published.

Core fact: The incidence of allergic diseases has been increasing. It is thought that lack of exposure to microbes may play a role.

Myth: Vaccines cause allergic diseases.

Explanation: Extensive research shows that, if anything, vaccines may have a protective effect against allergic disease.

Many studies have explored this issue. A few have shown a positive association, but the majority show no association or a negative association. The international scientific community generally accepts that vaccines do not lead to allergies and in fact have a small protective effect against the development of allergy.2

It is especially important that children with asthma be given all recommended vaccines, as catching a disease like pertussis or influenza can worsen asthma.10 In New Zealand, influenza vaccination is particularly recommended for children with asthma because of this risk.

The 2012 Institute of Medicine review of adverse events rejected any causal relationship between inactivated influenza vaccine and asthma exacerbation or reactive airway disease episodes in children and adults.8

Core fact: On-time vaccination is associated with a reduced risk of hospitalisation for diseases such as pertussis and pneumococcal disease in children under 1 year of age.

Myth: Vaccines cause cot death.

Explanation: Vaccines may reduce the risk for cot death.

Sudden unexpected death in infancy (SUDI), also known as cot death, usually occurs in children aged under 12 months and is most common around age 3 months, when many immunisations are given. SUDI may occur by chance within a day or so of immunisation.11 There is no evidence that vaccination causes SUDI. Despite solid evidence against a link, the claims continue to be made.

There have been many studies that have conclusively shown that SUDI is not caused by immunisation.11 Some studies, including the New Zealand Cot Death Study, found a lower rate of SUDI in immunised children.12 This is consistent with a Scandinavian study, which found that some cases of SUDI were probably caused by undiagnosed pertussis.13 A large case-control study showed no increased risk of SUDI associated with immunisation,14 and a meta-analysis of nine case-control studies further suggested that immunisation is protective against SUDI.15 Consistent findings from several studies using a range of methods invalidate claims that associate vaccination with SUDI or cot death.16

Core fact: At birth the infant is exposed to thousands of microbes.

Myth: Vaccines ‘overload’ or ‘overwhelm’ the infant immune system.

Explanation: It is estimated that the infant immune system could respond to over 10,000 vaccines all at once.

There is no evidence of immune system ‘overload’, either theoretical or actual. The immune system is able to deal with an extraordinarily large number of different antigens at any one time.

Every day we all come into contact with viruses, bacteria and other agents to which the immune system responds. Any demands placed on the immune system by vaccines are minuscule compared to its ability to respond.

Vaccines have very few antigens in them. The number of immunogenic proteins and polysaccharides in modern vaccines has decreased dramatically compared with early vaccines because of advances in vaccine technology. For example, early whole-cell pertussis vaccines contained around 3,000 immunogenic proteins, compared with two to five in the modern acellular pertussis vaccines. In spite of an increase in the number of vaccines on the Schedule, an infant now receives far fewer immunogenic proteins and polysaccharides than with earlier vaccines.17 There are considerably more antigens in the organisms that cause disease than in the vaccines.

Explanation: Delaying immunisation for fear that an infant is too young leaves the infant vulnerable to disease, particularly pertussis and pneumococcal diseases. Infants delayed for their pertussis vaccinations are 4–6 times more likely to be hospitalised with the disease.18 On-time vaccination is important.

Core fact: Vaccines induce immunity through natural processes.

Myth: It is better to get ‘natural immunity’ than get vaccinated.

Explanation: Some vaccines induce better protection than that resulting from natural disease. Examples are tetanus, HepB and HPV, and protein conjugate polysaccharide vaccines administered to children aged under 2 years (Hib and PCV). There is no evidence that experiencing vaccine-preventable diseases has any benefit on health; on the contrary, these diseases are serious and sometimes fatal. Vaccinated people have fewer diseases than unvaccinated people.

Core fact: The scientific evidence shows there is no association between HPV vaccines and autoimmune conditions.

Myth: HPV vaccines cause autoimmune conditions.

Explanation: Several large cohort studies have been conducted to investigate the link between HPV vaccine and autoimmune conditions.19, 20, 21, 22, 23 No association has been found in these studies.

Core fact: The quadrivalent human papillomavirus vaccine has reduced cervical disease in countries using the vaccine, and Australia has almost eliminated genital warts.

Myth: HPV vaccines cause postural orthostatic tachycardia syndrome (POTS), complex regional pain syndrome (CRPS) and chronic fatigue syndrome (CFS).

Explanation: There is no scientific evidence that links POTS, CRPS or CFS with HPV vaccination.

POTS is a condition in which tachycardia occurs when a patient moves from a supine position to upright. The condition is associated with a collection of other symptoms, which include palpitations, light-headedness, weakness, blurred vision, headache, extreme fatigue, nausea, syncope and sleep disturbance. Up to 50 percent of people with POTS have an antecedent viral illness and 25 percent have a family history of similar complaints. There is an overlap between POTS and CFS.24

CRPS describes a variety of disorders characterised by pain that is disproportional to the inciting event. In children and adolescents it often presents as a painful mottled swollen limb with allodynia and hyperalgesia. Girls are six times more likely to be affected than boys and the peak age of onset is at age 12–13 years. Often minor trauma is the inciting event, but around one-third of people with CRPS are unable to recall an inciting injury or trauma.25

CFS is a disorder characterised by extreme fatigue that cannot be explained by an underlying medical condition. The causes are unknown but it has been linked to infection with Epstein–Barr virus and human herpesvirus 6.

Cases of these disorders have been reported in association with HPV vaccination, particularly in the media, and social media. The variable time between vaccination and onset of symptoms, lack of consistent symptoms and a reporting rate that remains below the expected rate for these syndromes all point to HPV vaccine not being the cause of these conditions.26

Post-marketing surveillance systems globally continue to monitor the safety of HPV vaccination programmes.27, 28, 29 The WHO’s Global Advisory Committee on Vaccine Safety has systematically reviewed HPV vaccine safety and has not found any safety issue that would alter its recommendations for use.30 The main challenge with HPV vaccine is communicating its excellent safety profile.31

Core fact: Everything is made of chemicals and any chemical can be toxic, even water.

Myth: Vaccines contain toxic chemicals, viruses and cells.

Explanation: Vaccine ingredients are not toxic in the amounts present in a vaccine. It is the dose that differentiates a poison from a harmless substance, essential substance or a medicine.

Most of the ingredients in vaccines are present already in our bodies and we consume them in some way every day. For example, aluminium is the most common metallic element on earth, and the body makes and uses formaldehyde for synthesising deoxyribonucleic acid (DNA).

For more information, see the IMAC factsheet Vaccine Ingredients (available at www.immune.org.nz/resources/written-resources).

Core fact: With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction. – Stanley Plotkin34

Myth: Vaccination has played little role in controlling disease.

Explanation: Vaccine programmes have controlled or eliminated polio, tetanus, diphtheria, pertussis, Haemophilus influenzae type b, hepatitis B, pneumococcal disease, meningococcal disease, rotavirus, human papillomavirus, varicella, hepatitis, yellow fever, measles, mumps, rubella and others, in populations where vaccines have been used.

Improvements in living conditions and medical care have reduced the chances of dying from infectious disease, but without immunisation most people will still acquire vaccine-preventable infections. For example, measles, which spreads through the air, is largely unaffected by improvements in living conditions other than reduced overcrowding. Indigenous cases of measles, mumps and rubella have been eliminated from Finland over a 12-year period using a two-dose MMR vaccine schedule given between 14 and 16 months and at age 6 years.35 In September 2016, the Region of the Americas was the first WHO region to be declared free of measles.

Core fact: No vaccine is 100 percent effective and some immunised children will get the disease.

Myth: Vaccines do not work, as most cases of disease are in immunised children.

Explanation: As immunisation coverage increases, the proportion of cases that occur in children who have been immunised compared with those who are unimmunised increases. There is a mathematical relationship between vaccine effectiveness, immunisation coverage and the proportion of cases that are immunised.

To see this clearly, imagine a group of 100 children. If 90 percent of children are given a vaccine with 90 percent efficacy, then:

This means that in the situation of exposure to the infection in a community, we expect that nearly half the cases of disease will be in immunised children, even though only 10 percent of immunised children were susceptible.

Of course, if all 100 children had been vaccinated only 10 would be susceptible to disease. As vaccine uptake rises, the proportion of cases of disease that occur in vaccinated people increases dramatically, but the absolute number of cases of disease falls to very low levels. Failing to provide the denominators (how many vaccinated and how many unvaccinated) can lead to misunderstanding.

For pertussis, where the protection following immunisation lasts only four to six years, immunised children can be infected but the resultant illness is usually milder, with fewer serious consequences and at an older age than if they had not received vaccine. The disease is most severe in infants, but adolescents and adults contribute to the carriage and spread of the disease (see sections 14.2 and 14.3).

For further details on the effectiveness of vaccines, see the ‘Written resources’ section of the IMAC website (www.immune.org.nz/resources/written-resources).

3.3 Addressing immunisation issues in a constantly changing environment

In the past few years the internet has exploded with a variety of forums that disseminate anti-immunisation material effectively. It is no longer practical to prepare official rebuttals to each new article. Fortunately, the internet also facilitates the rapid communication of scientific commentary on new myths as they appear. There are several scientists who regularly address immunisation myths in the form of regular blogs. In addition, some organisations provide position statements and discussion forums.

Below are some organisations and individuals who write and provide information related to immunisation scares, myths and pseudoscience that can help you to understand the myth. They can be a source of new information that may help to address a concern and ask a question, and may be useful resources for parents.

While the format is often colloquial, the writers are respected scientists who volunteer commentary against the abuse of science and evidence-based medicine.

3.3.1 Science blogs

Below are science blogs that frequently deal with immunisation issues.

References

  1. Department of Health and Ageing. 2016. Rotavirus. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-17 (accessed 29 September 2016).
  2. Offit PA, Hackett CJ. 2003. Addressing parents’ concerns: do vaccines cause allergic or autoimmune diseases? Pediatrics 111(3): 653–9. URL: http://pediatrics.aappublications.org/content/111/3/653 (accessed 7 November 2013).
  3. American Academy of Pediatrics. 2015. Varicella-zoster virus infections. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  4. Hilton S, Petticrew M, Hunt K. 2006. ‘Combined vaccines are like a sudden onslaught to the body’s immune system’: parental concerns about vaccine ‘overload’ and ‘immune-vulnerability’. Vaccine 24(20): 4321–7.
  5. MacDonald N, Finlay J, Canadian Paediatric Society – Infectious Diseases and Immunization Committee. 2013 (reaffirmed 1 February 2016). Position Statement: Working with vaccine hesitant parents. Paediatrics and Child Health 18(6): 265–7. URL http://www.cps.ca/documents/position/working-with-vaccine-hesitant-parents (accessed 25 January 2017).
  6. Cook J, Lewandowsky S. 2011. The Debunking Handbook. URL: https://skepticalscience.com/docs/Debunking_Handbook.pdf (accessed 25 January 2017).
  7. Demicheli V, Rivetti A, Debalini MG, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database of Systematic Reviews 2012, Issue 2, Art. No. CD004407. DOI: 10.1002/14651858.CD004407.pub3 (accessed 27 August 2013).
  8. Institute of Medicine: Committee to Review Adverse Effects of Vaccines. 2012. Adverse Effects of Vaccines: Evidence and causality. URL: http://www.nap.edu/catalog.php?record_id=13164 (accessed 29 October 2013).
  9. Immunize Action Coalition. 2010. Evidence shows vaccines unrelated to autism. Vaccine Concerns: Autism. URL: www.immunize.org/catg.d/p4028.pdf (accessed 31 October 2013).
  10. Department of Health and Ageing. 2013. Myths and Realities: Responding to arguments against vaccination. URL: www.health.gov.au/internet/immunise/publishing.nsf/content/uci-myths-guideprov (accessed 7 November 2013).
  11. Brotherton JML, Hull BP, Hayen A, et al. 2005. Probability of coincident vaccination in the 24 or 48 hours preceding sudden infant death syndrome death in Australia. Pediatrics 115(6): e643–6. DOI: 10.1542/peds.2004-2185 (accessed 4 February 2014).
  12. Mitchell EA, Stewart AW, Clements M. 1995. Immunisation and the sudden infant death syndrome: New Zealand Cot Death Study Group. Archives of Disease in Childhood 73(6): 498–501.
  13. Lindgren C, Milerad J, Lagercrantz H. 1997. Sudden infant death and prevalence of whooping cough in the Swedish and Norwegian communities. European Journal of Pediatrics 156(5): 405–9.
  14. Vennemann MMT, Butterfass-Bahloul T, Jorch G, et al. 2007. Sudden infant death syndrome: no increased risk after immunisation. Vaccine 25(2): 336–40.
  15. Vennemann MMT, Hoffgen M, Bajanowski T, et al. 2007. Do immunisations reduce the risk for SIDS? A meta-analysis. Vaccine 25(26): 4875–9.
  16. Medsafe. 2016. Sudden unexpected death in infants (SUDI): no causal link to vaccination. Prescriber Update 37(4): 56–7 URL: http://www.medsafe.govt.nz/profs/PUArticles/PDF/Prescriber%20Update%20December%202016.pdf (accessed 27 January 2017).
  17. Offit PA, Quarles J, Gerber MA, et al. 2002. Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant’s immune system? Pediatrics 109(1): 124–9.
  18. Grant CC, Roberts M, Scragg R, et al. 2003. Delayed immunisation and risk of pertussis in infants: unmatched case-control study. British Medical Journal 326(7394): 852–3. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153471/pdf/852.pdf (accessed 21 October 2013).
  19. Chao C, Klein NP, Velicer CM, et al. 2012. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. Journal of Internal Medicine 271(2): 193–203. DOI: 10.1111/j.1365-2796.2011.02467.x (accessed 29 October 2012).
  20. Arnheim-Dahlstroem L, Pasternak B, Svanstroem H, et al. 2013. Autoimmune, neurological and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. British Medical Journal 247: f5906. DOI: 10.1136/bmj.f5906 (accessed 10 December 2016).
  21. Grimaldi-Bensouda L, Guillemot D, Godeau B, et al. 2014. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. Journal of Internal Medicine 275(4): 398–408. DOI: 10.1111/joim.12155 (accessed 10 December 2016).
  22. Langer-Gould A, Qian L, Tartof SY, et al. 2014. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating disease. JAMA Neurology 71(12): 1506–13. DOI: 10.1001/jamaneurol.2014.2633 (accessed 10 December 2016).
  23. Scheller NM, Svanström H, Pasternak B, et al. 2015. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating disease of the central nervous system. Journal of the American Medical Association 313(1): 54–61. DOI: 10.1001/jama.2014.16946 (accessed 10 December 2016).
  24. Benarroch EE. 2012. Postural Tachycardia Syndrome: a heterogeneous and multifactorial disorder. Mayo Clinic Proceedings 87(12): 1214–25. DOI: http://dx.doi.org/10.1016/j.mayocp.2012.08.013 (accessed 9 December 2016).
  25. Borucki AN, Grecko CD. 2015. An update on complex regional pain syndromes in children and adolescents. Current Opinion in Pediatrics 27(4): 448–52.
  26. European Medicines Agency. 2015. Pharmacovigilance Risk Assessment Committee (PRAC): Assessment Report: Human papillomavirus (HPV) vaccines (EMA/762033/2015). URL: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/HPV_vaccines_20/Opinion_provided_by_Committee_for_Medicinal_Products_for_Human_Use/WC500197129.pdf (accessed 18 October 2016).
  27. Nguyen M, Ball R, Midthun K, et al. 2012. The Food and Drug Administration’s post-licensure rapid immunization safety monitoring program: strengthening the federal vaccine safety enterprise. Pharmacoepidemiology and Drug Safety 21(Suppl 1): 291–7. DOI: 10.1002/pds.2323 (accessed 26 December 2012).
  28. Kliewer EV, Demers AA, Brisson M, et al. 2010. The Manitoba human papillomavirus vaccine surveillance and evaluation system. [Erratum appears in Health Reports 2010; 21(3): 77.] Health Reports 21(2): 37–42.
  29. Gold MS, McIntyre P. 2010. Human papillomavirus vaccine safety in Australia: experience to date and issues for surveillance. Sexual Health 7(3): 320–4.
  30. World Health Organization. 2015. Global Advisory Committee on Vaccine Safety, 2–3 December 2015. Weekly Epidemiological Record 91(3): 21–31. URL: http://www.who.int/vaccine_safety/committee/reports/wer9103.pdf?ua=1 (accessed 12 October 2016).
  31. World Health Organization. 2016. Meeting of the Strategic Advisory Group of Experts on Immunization, April 2016 – conclusions and recommendations. Weekly Epidemiological Record 91(21): 266–84. URL: http://www.who.int/wer/2016/wer9121.pdf?ua=1 (accessed 12 October 2016).
  32. Eickhoff TC, Myers M. 2002. Workshop summary: aluminum in vaccines. Vaccine 20(Suppl 3): 1–4.
  33. Petrovsky N. 2015. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs. Drug Safety 38(11): 1059–74. DOI: 10.1007/s40264-015-0350-4 (accessed 25 January 2017).
  34. Plotkin SA, Mortimer EA. 1988. Vaccines. Philadelphia, PA: Saunders.
  35. Peltola H, Heinonen OP, Valle M, et al. 1994. The elimination of indigenous measles mumps and rubella from Finland by a 12-year, two-dose vaccination program. New England Journal of Medicine 331(21): 1397–1402.

4 Immunisation of special groups

In this chapter:

4.1 Pregnancy and lactation

4.2 Infants with special immunisation considerations

4.3 Immunocompromised individuals of all ages

4.4 Immigrants and refugees

4.5 Travel

4.6 Occupational and other risk factors

References

This chapter discusses the special immunisation requirements of individuals at risk of vaccine-preventable diseases due to certain conditions or underlying disease, or through their occupation or other risk factors. The topics covered are:

Note: Vaccinators are advised to regularly check the Pharmaceutical Schedule and any online updates (www.pharmac.govt.nz) for changes to funding decisions for special groups.

4.1 Pregnancy and lactation

4.1.1 For women planning pregnancy

Women who are planning pregnancy should know whether they are immune to rubella (see section 18.5.3) and varicella (see section 21.5.4).

MMR

Two doses of MMR vaccine are recommended and funded for women who are susceptible to measles, mumps and/or rubella (see sections 11.5, 13.5 and 18.5). Women who are to receive the rubella vaccine (as MMR) are advised to ensure they are not pregnant at the time of immunisation and for at least four weeks afterwards, although there is no current evidence that rubella vaccine is teratogenic (see section 18.6.1). If the mother is non-immune, two doses of MMR vaccine, separated by four weeks, should be given after delivery.

Varicella

VV is recommended (but not funded) for adults who are susceptible to varicella. Two doses are given, four to eight weeks apart (see section 21.5 and the manufacturers’ data sheets for administration and dosing information). Women who are to receive VV are advised to ensure they are not pregnant at the time of immunisation and for at least four weeks afterwards.

4.1.2 During pregnancy

Inactivated vaccines are considered safe in pregnancy, but because of the theoretical possibility of harm to the fetus, live vaccines should not be administered to a pregnant woman. In some circumstances where there is increased risk of exposure to the microbe, the need for immunisation may outweigh any possible risk to the fetus.

See the relevant disease chapters, particularly rubella (section 18.8.3) and varicella (section section 21.8.6), for recommendations on managing exposure to diseases during pregnancy.

Influenza vaccine

The influenza vaccine is recommended and funded for pregnant women, and should be offered to women at any stage of pregnancy, as soon as the annual influenza vaccine becomes available (see section 10.5). Both the pregnant woman and her fetus are at increased risk of influenza complications; influenza immunisation is therefore recommended during pregnancy to reduce this risk.

Maternal influenza immunisation also offers protection to the neonate through maternal antibody transfer.1 Influenza vaccines are not registered or effective in infants aged under 6 months, therefore immunisation during pregnancy confers protection to newborns and infants who are too young to have received vaccination at the time of exposure.1, 2 Maternal influenza immunisation is significantly associated with reduced risk of influenza virus infection3 and hospitalisation for an influenza-like illness in infants up to 6 months of age,4, 5 and increased influenza antibody titres are seen in infants through to age 2–3 months.1

Influenza immunisation during pregnancy may also reduce the incidence of stillbirth. In an Australian study, stillbirth was 51 percent less likely among vaccinated mothers compared to unvaccinated mothers.6

There is no evidence that influenza vaccine prepared from an inactivated virus causes harm to the fetus or to the neonate.7

Pertussis vaccine (Tdap)

Pertussis is a severe infection in infants too young to have been immunised. Vaccination with Tdap should be offered in every pregnancy (currently funded between 28 and 38 weeks’ gestation, see section 14.5) to protect the mother and so that antibodies can pass to the fetus; post-partum maternal vaccination will reduce the risk of a mother infecting her baby but does not have the added benefit of providing passive antibodies.

In October 2012 the UK introduced a pertussis vaccination programme for pregnant women in response to a nationwide pertussis outbreak. An observational study of the programme in England estimated vaccine effectiveness at 91 percent (95% CI: 84–95) for preventing pertussis in infants aged under 3 months.8 This high vaccine effectiveness is likely to be a result of protection of infants by both passive antibody transfer and reduced exposure to maternal disease.8

An observational study of the safety of the UK’s maternal pertussis vaccination programme found no evidence of an increased risk of any of the extensive predefined list of adverse events related to pregnancy.9 In particular, there was no evidence of an increased risk of stillbirth.

Close contacts

The confirmation of pregnancy should act as a trigger to update the pertussis vaccination status of all close contacts. This includes making sure siblings have received their routine scheduled vaccines (funded for children aged under 18 years) and offering Tdap to adults, although this is not currently funded.

4.1.3 Breastfeeding and post-partum

MMR

MMR vaccine (two doses) is recommended (and funded) after delivery for women who are susceptible to any of the three diseases. Breastfeeding is not a contraindication to MMR vaccine.

Pertussis vaccine (Tdap)

To protect the newborn infant, Tdap is recommended (but not funded) for close contacts of newborns, including women who were not vaccinated during pregnancy.

Varicella

VV is recommended (but not funded) for all susceptible adults. Pregnant women who are non-immune can receive VV after delivery.

VV for the mother is recommended (and funded) after delivery if the baby is immunocompromised and the mother is susceptible to varicella (see sections 4.3 and 21.5).

4.2 Infants with special immunisation considerations

4.2.1 Preterm and low birthweight infants

Vaccination as per the Schedule (ie, at the usual chronological age, with the usual vaccine dosage and interval) is recommended for preterm infants and infants with low birthweight. If an infant is in hospital when 6 weeks old, the scheduled vaccines, including rotavirus vaccine, should be given. If standard infection control precautions are maintained, the risk of transmission of vaccine strain rotavirus will be minimal.10

Note that there is a potential risk of apnoea in infants born before 28 weeks’ gestation. If a preterm infant had apnoeas following immunisation in hospital (6‑week and/or 3-month event), readmission for the next infant immunisation and respiratory monitoring for 48 to 72 hours may be warranted,11 but do not avoid or delay immunisation.

Hepatitis B vaccine

All preterm and low birthweight infants born to HBsAg-positive mothers should be managed the same way as term infants and receive immunoprophylaxis (HBIG and HepB) as soon as possible after birth (see section 8.5.2). They should continue routine immunisation as per the Schedule, starting at age 6 weeks.

Influenza vaccine

Preterm infants who develop chronic lung disease are recommended to receive influenza vaccine once they are aged 6 months or older, and a second dose four weeks later (influenza vaccine is usually available from March each year). Influenza vaccine is recommended (but not funded) for close contacts of preterm infants, including children (see section 10.5).

Pertussis vaccine (for contacts)

It is essential that siblings of preterm infants be up to date with immunisations to reduce the risk of pertussis transmission to vulnerable infants (see section 14.5). Adolescents should have received Tdap in year 7 as part of the Schedule. Pertussis-containing vaccine is funded for primary and catch-up immunisation of all children aged under 18 years (see Appendix 2 for catch-up schedules).

Tdap is recommended (but not funded) for adult contacts of young infants, with the exception of funded Tdap vaccine for pregnant women from 28 to 38 weeks’ gestation.

Pneumococcal vaccines (PCV10, PCV13 and 23PPV)

4.2.2 Infants with congenital heart disease

4.2.3 Infants with liver and renal disease

Some infants with congenital biliary or renal conditions are likely to need transplantation. An accelerated immunisation schedule for these infants is provided in Table 4.1. The aim of the accelerated schedule is to maximise protection against vaccine-preventable diseases and to deliver live viral vaccines prior to transplantation and immunosuppression.

Infants with biliary atresia may have polysplenia (functional hyposplenia) (see section 4.3.4).

Other chronic kidney diseases also warrant extra immunisations (see section 4.3.3).

Table 4.1: Accelerated immunisation schedule (funded) for infants in whom liver or kidney transplant is likely

Refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions.

Age Immunisation/serology Comments
6 weeks Usual Schedule, but use PCV13 (Prevenar 13) instead of PCV10 (Synflorix) Do not start earlier than age 6 weeks.
3 months Usual Schedule, but use PCV13 instead of PCV10  
MenCCV (NeisVac-C)  
5 months Usual Schedule, but use PCV13 instead of PCV10  
MenCCV (NeisVac-C)  
7 months MMR (Priorix) MMR should not be given within 1 month of predicted transplant.
Varicella (Varilrix) In general, VV should not be given within 1 month of predicted transplant but may be given at the discretion of the specialist.
Hep A (Havrix Junior)  
Anti-HBs serology If anti-HBs is negative, give a further 3 doses of monovalent HepB vaccine, 4 weeks apart (HBvaxPRO; use the 10 µg adult dose).
12 months PCV13 (Prevenar 13)  
MMR (Priorix) MMR should not be given within 1 month of predicted transplant.
Varicella (Varilrix) In general, VV should not be given within 1 month of predicted transplant but may be given at the discretion of the specialist.
MenCCV (NeisVac-C)  
13 months DTaP-IPV-HepB/Hib (Infanrix‑hexa)  
MMR (Priorix) MMR should not be given within 1 month of predicted transplant.
Hep A (Havrix Junior) If Hep A and HepB are due at the same time, consider using combined Hep A-HepB vaccine (Twinrix; not funded).
24 months 23PPV (Pneumovax 23) Revaccinate once after 5 years.
MCV4-D (Menactra) 2 doses of MCV4-D, 8 weeks apart, and at least 4 weeks after last PCV13.a Give a booster after 3 years, then 5-yearly.
4 years Usual schedule:
DTaP-IPV (Infanrix-IPV)
 
MMR (Priorix)

MMR not required if received 2 doses after age 12 months; contraindicated if post-transplant.

MMR can only be given if pre‑transplant.

From age 9 years HPV9 vaccine (Gardasil 9) 3 doses at 0, 2 and 6 months.b Funded pre- or post-transplant. If given early, they do not require the usual Schedule doses in year 7/8 (age 11/12 years).
11 years Usual schedule:
Tdap (Boostrix)
 
6 months post-transplant HepB (HBvaxPRO), plus anti-HBs serology before and 1 month after the initial HepB series

3 doses of HepB vaccine (5 µg).

If HepB was not previously given, and anti-HBs is negative, give 3 doses of HepB vaccine (10 µg).

If there is an inadequate immune response to the initial 3-dose HepB series, give a further 3 doses (10 µg).

23PPV If at least 24 months old and not given pre-transplant. Revaccinate once after 5 years.
Annually Influenza (Influvac) Recommended for patients (funded) and all family members (not funded). For patients (from age 6 months) and family members aged under 9 years, give 2 doses 4 weeks apart in the first year, and 1 dose in subsequent years.
Household contacts of transplant patients National Immunisation Schedule vaccines Immune-competent siblings and other household contacts may receive all the Schedule vaccines, and should be fully vaccinated for age.
Varicella (Varilrix) Two doses of VV are funded for susceptible household contacts of transplant patients.
  1. Give MCV4-D at least 4 weeks after PCV1312, 13 (see section 12.4.4).
  2. Individuals who started with HPV4 may complete their remaining doses with HPV9.

Source: Starship Children’s Health.

4.2.4 Asplenic infants

No vaccines are contraindicated for infants with functional or anatomical asplenia. The usual National Immunisation Schedule should be followed (replacing PCV10 with PCV13), with the addition of age-appropriate pneumococcal polysaccharide, meningococcal conjugate and influenza vaccines, as discussed in section 4.3.4.

4.2.5 Infants exposed to hepatitis B, with mothers with chronic HBV infection

Infants exposed to maternal hepatitis B infection require a birth dose of HepB and HBIG (see section 8.5.2).

4.2.6 Immune-deficient infants

Diagnosis of immune deficiency is often not made before children start their immunisation schedules. However, no parenteral live virus vaccines are given on the Schedule in the first year of life.

Rotavirus vaccine

Rotavirus vaccine is an oral, live, attenuated viral vaccine, which should not be given when severe combined immune deficiency (SCID) has been diagnosed. There have been case reports of rotavirus vaccine accidentally administered to infants with SCID, leading to chronic diarrhoea and failure to thrive.14, 15, 16 In infants with milder immune deficiency, rotavirus vaccine may cause prolonged shedding of the vaccine virus, but it is unlikely to cause harm.

There is little data on rotavirus vaccination in infants born to mothers on immunosuppressive therapies. Certain immunosuppressive medications, such as disease-modifying anti-rheumatic drugs (DMARDs), readily cross the placenta and can be detectable some months later.10 Infants of mothers who received DMARDs during pregnancy that are monoclonal antibodies (eg, adalimumab/Humira) should not be vaccinated with live rotavirus vaccines until theoretical concerns about safety are clarified.17 See Table 4.3 for a list of the highly immunosuppressive medications that readily cross the placenta.

BCG vaccine

BCG, being a live bacterial vaccine against TB, can cause disseminated disease in certain rare immune deficiencies. In the past few years, eligibility criteria for neonatal BCG have been restricted (see chapter 20) and universal antenatal human immunodeficiency virus (HIV) screening introduced, thus reducing the risk of BCG being given to a child with an undiagnosed immune deficiency.

For infants whose mothers received DMARDs during pregnancy that are monoclonal antibodies (eg, adalimumab, infliximab; see Table 4.3), BCG vaccination should be delayed until the infant is at least 8 months old.18

(See also section 4.3.)

4.2.7 Infants with HIV

Infants with HIV infection who do not have severe immunosuppression should follow the routine Schedule (replacing PCV10 with PCV13) and are eligible to receive funded meningococcal, varicella (two doses) and influenza vaccines, plus pneumococcal polysaccharide vaccine from age 2 years. (See ‘HIV infection’ in section 4.3.3.)

4.2.8 Other conditions

All infants with the following conditions should receive the routine Schedule vaccines, plus the additional vaccines as described.

4.3 Immunocompromised individuals of all ages

Individuals with chronic conditions, an immune deficiency, or who are immunosuppressed for underlying disease control are at increased risk or severity of infectious diseases. These individuals should be immunised as a matter of priority. Special care is required with some live vaccines. When considering immunising such individuals, seek advice from their specialist. See also the ‘Contraindications and precautions’ section in each disease chapter and the vaccine data sheets.

The following definitions are used in this Handbook:

4.3.1 Introduction

The nature and degree of immunocompromise determines the safety and effectiveness of vaccines. Immune deficiency conditions can be divided into primary and secondary. Primary immune deficiencies that present in childhood are generally inherited, and include antibody deficiency (disorders of B lymphocytes or antibody production), defects of cell-mediated immunity (disorders of T lymphocytes, which most often present as combined defects affecting antibody production as well), and defects of complement and phagocytic function19 (see section 4.3.2). Secondary immune deficiencies are acquired, and occur in people with HIV, people with malignant neoplasms, in organ transplant recipients, and in people receiving immunosuppressive treatment, chemotherapy or radiotherapy.19

Live parenteral vaccines (these include MMR, varicella and BCG) should not in general be given to individuals who are severely immunocompromised, because of the risk of disease from vaccine strains. Subunit and inactivated vaccines are safe to administer, although the response of immunocompromised individuals to these inactivated vaccines may be inadequate. For comment on rotavirus vaccine see section 4.2.6 above.

Specific serum antibody titres can be determined to guide immunisation requirements for some vaccines and the future management of disease exposures.

Certain immune deficiencies result in specific disease susceptibility. For example, pneumococcal and meningococcal vaccines are recommended for those with poor or absent splenic function or certain complement deficiencies, because of increased infection risk from encapsulated bacteria. Influenza and varicella vaccines are recommended for individuals with splenic dysfunction, asplenia and phagocyte function deficiencies, both to prevent the diseases and to reduce the risk of secondary bacterial infections. See section 4.3.4 for recommendations for individuals with splenic dysfunction or asplenia.

Household contacts

Infants in the household should receive rotavirus vaccine at the usual Schedule ages: there are no reported cases of symptomatic infection in immunocompromised contacts.20 There is no risk of transmission of MMR vaccine viruses to the immunocompromised individual.

VV can be given safely to the household contacts of immunocompromised individuals. However, where a vaccinee (household contact) develops a vesicular rash, then that individual should be isolated from the immunosuppressed individual for the duration of the rash. VV is funded for non-immune household contacts of patients who are immunocompromised or undergoing a procedure or treatment leading to immunocompromise.

4.3.2 Primary immune deficiencies

Live vaccines are contraindicated for all individuals with T lymphocyte-mediated immune deficiencies and combined B- and T-lymphocyte disorders.19 Most of these individuals will be on intravenous immunoglobulin (IVIG) replacement therapy, which provides passive protection against most vaccine-preventable infections.

Hib, PCV13, 23PPV and Td vaccines may be used in testing for primary immune deficiencies, on the recommendation of an internal medicine physician or paediatrician.

Influenza vaccine is funded for all immune-deficient individuals. Regardless of their age, all immune-deficient individuals who receive influenza vaccine for the first time are recommended to receive two vaccine doses at least four weeks apart, and one dose annually after that.21

Once an immunodeficiency is recognised, PCV13 should replace PCV10 in the routine schedule (see sections 15.5.2 and 15.5.3).

Below is a summary of the appropriate immunisations for individuals with primary immune deficiencies.19 Seek specialist advice. (See also Table A6.1 in Appendix 6 of this Handbook.)

B lymphocyte deficiencies (humoral)

(Humoral means the development of circulating antibody.)

X-linked, agammaglobulinaemia and common variable immune deficiency

The efficacy of any vaccine that is dependent on a humoral response, such as 23PPV, is doubtful, but all inactivated vaccines are safe.

Selective IgA deficiency

All vaccines are probably effective.

T lymphocyte deficiencies (cell-mediated and humoral)
Complete defects (eg, SCID) and partial defects (eg, Wiskott–Aldrich syndrome, most patients with DiGeorge syndrome)

The efficacy of any vaccine depends on the degree of immune deficiency.

Complement deficiencies
Deficiency of early components (C1, C4, C2, C3)

All routine vaccines are probably effective.

Deficiency of late components (C5–9), properdin, factor B

All routine vaccines are probably effective.

Phagocytic function deficiencies
Chronic granulomatous disease, leukocyte adhesion defect, myeloperoxidase deficiency

All routine vaccines are probably effective.

4.3.3 Secondary (acquired) immune deficiencies

The following sections provide recommendations for individuals with diseases or therapy causing immunocompromise.

The ability of individuals with secondary immune deficiency to develop an adequate immunological response depends on the type of immune deficiency and/or and the intensity of immunosuppressive therapy.

Before commencing a therapy that would be expected to cause significant immunosuppression, a full vaccination history should be obtained. Then, if circumstances permit, such as prior to commencing immunosuppressive therapy for rheumatological disease or prior to solid organ transplant, vaccination should be completed (including HPV from age 9 years) and additional non-routine vaccines (eg, varicella for children or zoster vaccine for certain adults [see section 22.6]; and meningococcal) may be appropriate. Similarly, in diseases such as chronic renal failure, where immune impairment is likely to be progressive, early administration of vaccines may result in better antibody responses. If immediate treatment is required it should not be delayed to allow for vaccination. Live viral vaccines (MMR and VV) should only be given if the patient is non-immune, is not severely immunocompromised and is four or more weeks prior to commencement of immunosuppressive therapy. VV may be given at a shorter interval at the discretion of the specialist.

When immunosuppressive therapy is discontinued, immune recovery usually takes between 3 and 12 months.

Influenza vaccine is funded for immunocompromised individuals before each influenza season, and is recommended three to four weeks after chemotherapy for malignant neoplasm is completed, once both the peripheral granulocyte and lymphocyte counts are >1.0 × 109/L. Regardless of their age, all immunocompromised individuals who receive influenza vaccine for the first time are recommended to receive two vaccine doses at least four weeks apart, and one dose annually after that.21

Individuals receiving corticosteroids

The minimum amount of corticosteroid administration sufficient to cause immunosuppression is not well defined, and is dependent on dose, duration and the underlying disease. Many clinicians consider a daily dosage equivalent to 2 mg/kg prednisone or greater, or a total daily dosage of 20 mg or greater, particularly when given for 14 days or more, is sufficient to raise concern about the safety of live virus vaccines.

The following guidelines may be used for the safe administration of live virus vaccines to individuals on corticosteroids. Table 4.2 provides a summary of the guidelines for individuals on high-dose corticosteroids.

Live virus vaccines can be administered to:

Live virus vaccines should not be administered to:

Note: These guidelines are intended to ensure safety of administration of the live virus vaccine; optimal vaccine immunogenicity may not be achieved.

Table 4.2: Guidelines for live virus vaccine administration for individuals on high-dose corticosteroids
  Infants and children <10 kg Children ≥10 kg and adults Administration of live viral vaccines after cessation of corticosteroids22
High dose
<14 days
>2 mg/kg
Daily or on alternate days
>20 mg/day Can be given immediately on discontinuation, but delay 2 weeks if possible
High dose
>14 days
>2 mg/kg
Daily or on alternate days
>20 mg/day Delay for 4 weeks

Source: IMAC

Other immunosuppressive agents (eg, for autoimmune diseases, rheumatological diseases, inflammatory bowel disease)

In recent years there has been rapid development of immunosuppressive agents, particularly targeted biological therapies, and an increasing number of patients are receiving such therapies.17 Table 4.3 lists the categories of agents available, according to their potential for immunosuppression.

As a general guide, low-level immunosuppression includes treatment with prednisone <2 mg/kg with a maximum of 20 mg/day; methotrexate ≤0.4 mg/kg/week; azathioprine ≤3 mg/kg/day; or 6‑mercaptopurine ≤1.5 mg/kg/day. High-level immunosuppression regimens include treatment regimens with higher than the above doses, and those on biological agents such as tumour necrosis factor antagonists or rituximab. Combination therapies increase the level of immunosuppression.

See also the Starship Clinical Guideline Immunosuppression and Infection in Rheumatology Patients (available at www.starship.org.nz/for-health-professionals/starship-clinical-guidelines/i/immunosuppression-and-infection-in-rheumatology-patients/).

Table 4.3: Immunotherapy agents for immune-mediated inflammatory disease

Note: This is not an extensive list of immunotherapy agents; new agents are continually being developed. Seek specialist advice.

Corticosteroids Immunosuppressive agents
Disease modifying anti-rheumatic drugs (DMARDs)
Targeted biological therapies Cytotoxics

Prednisone

Prednisolone

Methyl-prednisolone

DMARDs I

Hydroxy-chloroquine

Leflunomide

Methotrexate

Sulphasalazine

DMARDs II

Azathioprine

Cyclosporin

Mycophenolate mofetil

Biological DMARDs

Abatacept

Anakinra

Rituximab

Tocilizumab

Ustekinumab

Anti-tumour necrosis factor DMARDs

Adalimumab

Etanercept

Infliximab

Cyclo-phosphamide

When these agents are used singly

Source: IMAC

Oncology patients

This section provides general guidelines for vaccination after cancer treatment. Specific vaccination questions should be discussed with an expert paediatrician, infectious diseases physician or oncologist. Annual influenza vaccine is recommended and can be given even while a patient is on treatment (two doses four weeks apart in the first year). Household contacts may be safely given MMR (funded; see chapter 11) and VV (funded; see ‘Household contacts’ in section 4.3.1, or section section 21.5); annual influenza vaccination is also recommended (not funded) for contacts (see section 10.5).

Vaccination after chemotherapy

Those who have received routine immunisations prior to cancer diagnosis do not need full re-immunisation.

Booster dose(s) of a diphtheria/tetanus/pertussis-containing vaccine, and hepatitis B, polio (IPV) and pneumococcal vaccines (PCV13 followed by 23PPV) should be given, starting not less than three months after chemotherapy has ended, when the lymphocyte count is >1.0 × 109/L. Live viral vaccines should be delayed for at least six months after chemotherapy, but MMR and VV should then be given to seronegative patients (for MMR, being seronegative to any of the three diseases justifies vaccination). The interval may need to be extended according to:

For children aged under 18 years, suggested age-appropriate schedules and worksheets are available on the Starship website (www.starship.org.nz/media/199142/immunisation_of_children_during_and_after_cancer_therapy_18_july_2014.pdf).

Vaccination after haematopoietic stem cell transplant (HSCT)/bone marrow transplant

Many factors can affect a transplant recipient’s immunity to vaccine-preventable diseases following a successful marrow transplant. These include the donor’s immunity, the type of transplant and the interval since the transplant, the continuing use of immunosuppressive drugs, and graft versus host disease. Some recipients acquire the immunity of the donor, but others lose all serological evidence of immunity.

Complete re-immunisation is recommended, starting with routine Schedule inactivated vaccines 12 months after bone marrow transplant (use Tdap for tetanus, diphtheria and pertussis immunisation if the child is aged 10 years or older).

Pneumococcal vaccines (PCV13 followed by 23PPV), meningococcal (conjugate C and quadrivalent conjugate), hepatitis B and a booster dose of Hib and IPV are all recommended.

Healthy survivors of bone marrow transplant can be given VV not less than two years after transplant, with MMR given four weeks later if VV tolerated. Second doses of MMR and VV should be given four weeks or more after the first doses, unless serological response to measles and varicella is demonstrated after the first dose. The vaccines should not be given to individuals suffering from graft versus host disease because of a risk of a resulting chronic latent virus infection leading to central nervous system sequelae.

For children aged under 18 years, suggested age-appropriate schedules and worksheets are available on the Starship website (www.starship.org.nz/media/199142/immunisation_of_children_during_and_after_cancer_therapy_18_july_2014.pdf).

Chronic kidney disease (CKD)

Immune response and duration of protection after immunisation decrease with advancing kidney disease, so routine Schedule and other recommended vaccines should be given as soon as kidney disease is recognised.

Individuals immunised during the early stages of CKD generally respond to immunisation, but the magnitude of response and/or more rapid waning of immunity have an influence on how well protected they are from infection or severe disease following immunisation. Cases of children developing a disease for which they have serological evidence of immunity have been reported.23

Patients should receive routine Schedule vaccines and annual influenza vaccine. Live viral vaccines are considered safe for individuals with CKD and minimal immunocompromise, but they are generally not recommended for individuals on immunosuppressive medicines because of the risk of disseminated disease from the vaccine virus.24 However, a number of small studies suggest that the risk of disseminated VV-related disease is small and can be managed with antiviral therapy, and that varicella immunisation is a significantly lower risk for immunosuppressed individuals than community-acquired disease.22

Individuals with nephrotic syndrome, kidney failure or end-stage kidney disease (CKD stages 4–5) have an increased risk of developing bacterial peritonitis and/or sepsis. Additional pneumococcal vaccines, a Hib booster, conjugate meningococcal vaccines and annual influenza vaccine are recommended.

Dialysis patients must be hepatitis B immune, with administration of repeated courses of HepB, of higher strength if required: the higher strength 40 µg HepB (HBvaxPRO) is funded for dialysis patients.

There is no relationship between immunisation and deterioration of renal function or a reduction in the efficacy of dialysis.23

A recommended immunisation schedule and worksheet for paediatric CKD stages 4–5 and dialysis patients is available on the Starship website (www.starship.org.nz/media/286703/renal_-_vaccination_record_for_paediatric_ckd_july_2014.pdf).

Solid organ transplants

An accelerated immunisation schedule is recommended for individuals likely to be listed for solid organ transplant (see Table 4.1 for infant recommendations). Specialist advice should be sought in these situations.

Individuals older than 12 months who have been scheduled for solid organ transplantation should receive MMR and VV at least four weeks before the transplant. Measles antibody titres should be measured one to two years after the transplant; immunisation may be repeated if titres are low, but only if the level of immunosuppression permits. It is advisable to check other antibody titres annually and re‑immunise where indicated.

The use of passive immunisation with IG after exposure to measles or chickenpox should be based on the documentation of negative antibody titres, or where immune status is unknown. See chapter 15 for further information on pneumococcal immunisation for these individuals. VV is also funded for non-immune household contacts of transplant patients (see section 21.5).

In patients undergoing organ transplantation, pneumococcal vaccine (PCV13 first followed by 23PPV 8 weeks later, both funded) should be given at least two weeks before the transplant. Hepatitis A, hepatitis B, HPV, influenza, meningococcal conjugate and varicella vaccines are funded for transplant patients. (Re-)vaccination with age-appropriate DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap and Hib vaccines is also funded. (See the relevant disease chapters.)

HIV infection

All HIV-positive children, whether symptomatic or asymptomatic, are recommended to receive the routine Schedule vaccines, including MMR (if CD4+ ≥15%), rotavirus (infants only) and HPV (three doses from age 9 years). Asymptomatic children who are not severely immunocompromised are recommended to receive MMR vaccine at age 12 months to provide early protection against the three diseases.

The efficacy of any vaccine may be reduced in HIV-positive individuals, and antibody levels may wane faster than in individuals who are HIV‑negative. Although antiretroviral therapy may improve immune responses, it is unlikely these individuals will achieve the levels of antibodies seen in individuals who are HIV-negative. Serological testing and the need for additional doses (eg, of HepB, see section 8.5.7) should be discussed with the individual’s specialist.

Passive immunisation with IG may be required for individuals with HIV infection who are exposed to chickenpox or measles.

Tables 4.4 (children aged under 5 years when diagnosed), 4.5 (children aged 5 to under 18 years) and 4.6 (adults aged 18 years and older) summarise the additional vaccine recommendations and schedules for HIV-positive individuals.

Table 4.4: Children aged under 5 years when diagnosed with HIV: additional vaccine recommendations

Note: HIV-positive children should receive the routine Schedule vaccines, including rotavirus vaccine for infants, but see the MMR recommendations below. BCG should not be given. Vaccinators are advised to refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions.

Age at diagnosis Vaccine
(trade name)
Recommended vaccine schedule
Infants aged under 12 months when diagnosed PCV13
(Prevenar 13)

PCV13a at ages 6 weeks, 3, 5 and 15 months or age-appropriate catch-up schedule:

  • if commencing immunisation at ages
    7–11 months, give 2 doses of PCV13 at least 4 weeks apart, followed by a booster dose at age 15 months
  • for children aged 7–11 months who have completed the primary course with PCV10, give 1 dose of PCV13, followed by the scheduled PCV13 booster at age 15 months.
23PPV
(Pneumovax 23)

Following the completion of the PCV course, give 1 dose of 23PPV at age ≥2 years. There must be at least 8 weeks between the last PCV dose and the 23PPV dose.

Revaccinate once with 23PPV, 5 years after the first 23PPV.

Influenza
(Influvac)

Annual immunisation from age 6 months.

In the first year, give 2 doses 4 weeks apart, then 1 dose in each subsequent year.

MenCCV
(NeisVac-C)

and

MCV4-D (Menactra)

Use the age-appropriate MenCCV schedule:

  • if aged under 6 months at diagnosis, give 2 doses 8 weeks apart, with a booster at age 12 months
  • if aged 6–11 months at diagnosis, give 1 dose, with a booster at age 12 months.

At age 2 years, give 2 doses of MCV4‑Db 8 weeks apart, then a booster after 3 years, then 5-yearly.

Children aged 12 months to under 5 years when diagnosed PCV13
(Prevenar 13)

The PCV13a,c age-appropriate catch-up schedule is:

  • if commencing immunisation at ages 12 months or older, give 2 doses of PCV13,c 8 weeks apart
  • children aged >17 months who have completed the primary course of PCV10 but not received PCV13, give 1 dose of PCV13.c,d
23PPV
(Pneumovax 23)

Following the completion of the PCV course, give 1 dose of 23PPV at age ≥2 years. There must be at least 8 weeks between the last PCV dose and the 23PPV dose.

Revaccinate once with 23PPV, 5 years after the 1st 23PPV.

Influenza
(Influvac)

Annual immunisation.

In previously unvaccinated children, give 2 doses 4 weeks apart, then 1 dose in each subsequent year.

MMRe
(Priorix)

If CD4+ lymphocyte percentage is ≥15%:

  • give the 1st MMR dose at age 12 months, followed by the 2nd dose 4 weeks later.
Varicellae,f
(Varilrix)

If CD4+ lymphocyte percentage is ≥15%:

  • give 2 doses (starting 4 weeks after the 2nd MMR), at least 3 months apart.

MenCCV
(NeisVac-C) and

MCV4-D
(Menactra)

If aged 12–23 months at diagnosis, give 1 dose of MenCCV; followed by MCV4-Db at age 2 years, 2 doses 8 weeks apart; then a booster of MCV4-D after 3 years; then 5‑yearly.

If aged ≥2 years at diagnosis, give 2 doses of MCV4-Db 8 weeks apart; then a booster of MCV4‑D after 3 years; then 5-yearly.

  1. PCV13 replaces PCV10 (Synflorix) on the Schedule.
  2. Give MCV4-D at least 4 weeks after PCV1312, 13 (see section 12.4.4).
  3. If 23PPV has already been given (prior to any doses of PCV13) to children aged under 18 years, wait at least 8 weeks before administering PCV13.
  4. There are no safety concerns, regardless of the interval between the last dose of PCV10 and the 1st dose of PCV13.
  5. Only a single viral vaccine is recommended at each visit for individuals with HIV infection. A minimum interval of 4 weeks is required between live vaccine doses administered at different visits.
  6. Give VV on the advice of an HIV specialist.

Source: Starship Children’s Health.

Table 4.5: Children aged 5 to under 18 years when diagnosed with HIV: additional vaccine recommendations

Note: HIV-positive children should receive the routine Schedule vaccines, but see the MMR recommendations below. BCG should not be given. Vaccinators are advised to refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions.

Vaccine
(trade name)
Recommended vaccine schedule
HPV9
(Gardasil 9)
From age 9 years, give 3 doses of HPV at 0, 2 and 6 months.a,b
PCV13
(Prevenar 13)
For children who have not previously received PCV13, give 1 dose of PCV13.c
23PPV
(Pneumovax 23)

1 dose of 23PPV at least 8 weeks after the PCV13 dose.

Revaccinate once with 23PPV, 5 years after the 1st 23PPV.

Influenza
(Influvac)

Annual immunisation.

Regardless of age, if previously unvaccinated, give 2 dosesd 4 weeks apart. Then give 1 dose in each subsequent year.

MMRe
(Priorix)

If aged ≤13 years and CD4+ lymphocyte percentage is ≥15%, or

if aged ≥14 years and CD4+ lymphocyte count is ≥200 cells/mm3:

  • give 2 MMR doses at least 4 weeks apart.
Varicellae,f
(Varilrix)

If no history of varicella disease or immunisation, and

if aged ≤13 years and CD4+ lymphocyte percentage is ≥15%, or

if aged ≥14 years and CD4+ lymphocyte count is ≥200 cells/mm3:

  • give 2 doses (starting 4 weeks after 2nd MMR), at least 3 months apart.
MCV4-D
(Menactra)

Give 2 doses of MCV4-Dg 8 weeks apart, and:

  • if the 1st MCV4-D dose was given at age <7 years, give a booster after 3 years, then 5-yearly, or
  • if the 1st MCV4-D dose was given at age ≥7 years, give a booster dose every 5 years.
  1. Individuals who started with HPV4 may complete their remaining doses with HPV9.
  2. HPV9 is registered for use from age 9 years.
  3. If 23PPV has already been given (prior to any doses of PCV13) to children aged under 18 years, wait at least 8 weeks before administering PCV13.
  4. The 2nd dose of influenza vaccine is not funded for individuals aged 9 years and older.
  5. Only a single viral vaccine is recommended at each visit for individuals with HIV infection. A minimum interval of 4 weeks is required between live vaccine doses administered at different visits.
  6. Give VV on the advice of an HIV specialist.
  7. Give MCV4-D at least 4 weeks after PCV1312, 13 (see section 12.4.4).

Source: Starship Children’s Health.

Table 4.6: Adults aged 18 years and older when diagnosed with HIV: additional vaccine recommendations

Note: HIV-positive individuals should receive the routine Schedule vaccines, but see the MMR recommendations in the table below. BCG should not be given. Vaccinators are advised to refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions.

Vaccine
(trade name)
Recommended vaccine schedule
HPV9
(Gardasil 9)
For individuals aged 26 years and under:
3 doses of HPV9 at 0, 2 and 6 months.a
PCV13
(Prevenar 13)
1 dose of PCV13.b
23PPV
(Pneumovax 23)
Give a maximum of 3 doses of 23PPV in a lifetime, a minimum of 5 years apart. The 1st 23PPV dose is given at least 8 weeks after PCV13, the 2nd a minimum of 5 years later, the 3rd dose at age ≥65 years.
Influenza
(Influvac)
Annual immunisation. If previously unvaccinated, give 2 dosesc 4 weeks apart. Then give 1 dose in each subsequent year.
MMRd
(Priorix)

If born in 1969 or later and has no record of 2 previous MMR doses and CD4+ lymphocyte count is ≥200 cells/mm3:

  • give 1 or 2 MMR doses 4 weeks apart (so individual has 2 documented doses of MMR).
Varicellad,e
(Varilrix)

If no history of varicella disease or immunisation and CD4+ lymphocyte count is ≥200 cells/mm3:

  • give 2 doses at least 3 months apart.
Hepatitis B
(HBvaxPRO 10 μg)
If previously unvaccinated, give 4 doses, at 0, 1, 2 and 12 months.f
MCV4-D
(Menactra)
Give 2 doses of MCV4-D 8 weeks apart, then 1 dose every 5 years.g,h
  1. Individuals who started with HPV4 may complete their remaining doses with HPV9.
  2. If 23PPV has already been given (prior to any doses of PCV13) to adults aged 18 years and older, wait at least 1 year before administering PCV13.
  3. The 2nd dose of influenza vaccine is not funded for individuals aged 9 years and older.
  4. Only a single viral vaccine is recommended at each visit for individuals with HIV infection. A minimum interval of 4 weeks is required between live vaccine doses administered at different visits.
  5. Give VV on the advice of an HIV specialist.
  6. Consider screening for seroconversion after vaccination (see section 8.5.7). The 40 μg HepB dose may be recommended but is not funded.
  7. Give MCV4-D at least 4 weeks after PCV1312, 13 (see section 12.4.4).
  8. MCV4-D is registered for individuals aged 9 months to 55 years, but there are not expected to be any safety concerns when administered to adults older than 55 years.

Source: Starship Children’s Health.

4.3.4 Asplenia

There are three main reasons why an individual may not have a functioning spleen:

All asplenic individuals are at increased risk of fulminant bacteraemia, which is associated with a high mortality rate. The risk is greatest for infants, and probably declines with age and with the number of years since onset of asplenia.

The degree of risk of death from sepsis is also influenced by the nature of the underlying disease: it is increased 50 times (compared with healthy children) in asplenia after trauma and 350 times in asplenia with sickle cell disease, and the risk may be even higher post-splenectomy for thalassaemia.

Streptococcus pneumoniae is the pathogen that most often causes fulminant sepsis in these individuals. Other less frequent pathogens are Neisseria meningitidis, Haemophilus influenzae type b, other streptococci, Staphylococcus aureus, Escherichia coli and other gram-negative bacilli (eg, Klebsiella, Salmonella species and Pseudomonas aeruginosa). There is an increased fatality from malaria for asplenic individuals.

More information about asplenia is available on the Starship website (www.starship.org.nz/for-health-professionals/starship-clinical-guidelines/a/asplenia/).

Immunisation of asplenic individuals

No vaccines are contraindicated for individuals with functional or anatomical asplenia. It is important to ensure that the individual is up to date with the routine immunisations according to the National Immunisation Schedule, especially pneumococcal, Hib and MMR.

In addition to the routine Schedule vaccines, including VV at age 15 months or 11 years and HPV vaccine for individuals aged 26 years and under, the following vaccines are funded and/or recommended as soon as the asplenic condition is recognised. The immunisation schedules are age-dependent and are provided in Table 4.7 below.

For elective splenectomy, immunisations should be commenced as soon as possible and at least two weeks pre-operatively. For emergency splenectomy, commence immunisations two weeks post-operatively.

Prior to commencing immunisation, discuss with the individual’s specialist.

Table 4.7: Additional vaccine recommendations (funded and unfunded) and schedules for individuals with functional or anatomical asplenia

Note: Individuals with functional or anatomical asplenia should receive the routine Schedule vaccines, including varicella at age 15 months or 11 years and HPV for individuals aged 9–26 years, following recommended catch-up schedules if necessary. Funded vaccines are in the shaded rows, however vaccinators are advised to refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions.

Age at diagnosis Vaccine
(trade name)
Recommended vaccine schedule
Aged under 12 months when diagnosed with functional asplenia or pre-a or post-splenectomy PCV13
(Prevenar 13)

PCV13 at ages 6 weeks and 3, 5 and 15 months.

If commencing immunisation at ages
7–11 months, give 2 doses of PCV13 at least 4 weeks apart, followed by a booster dose at age 15 months.

23PPV
(Pneumovax 23)

Following the completion of the PCV course, give 1 dose of 23PPV at age ≥2 years. There must be at least 8 weeks between the last PCV dose and the 23PPV dose.

Revaccinate once with 23PPV, 5 years after the 1st 23PPV.

MenCCV
(NeisVac-C)

and

MCV4-D (Menactra)

Age-appropriate MenCCV schedule:

  • if aged under 6 months at diagnosis, give 2 doses 8 weeks apart, with a booster at age 12 months
  • if aged 6–11 months at diagnosis, give 1 dose, with a further dose at age 12 months.

At age 2 years, give 2 doses of MCV4‑Db 8 weeks apart, then a booster dose after 3 years, then 5‑yearly.

Influenza
(Influvac)

Annual immunisationc from age 6 months.

In the first year, give 2 doses 4 weeks apart, then 1 dose in each subsequent year.

Aged 12 months to under 18 years when diagnosed with functional asplenia or pre-a or post-splenectomy PCV13
(Prevenar 13)

PCV13d age-appropriate catch-up schedule:

  • previously unimmunised children aged ≥12 months to under 5 years require 2 doses of PCV13,d 8 weeks apart
  • previously unimmunised children aged 5 years to under 18 years require 1 dose of PCV13d
  • children aged >17 months who have completed the primary course of PCV10 but have not received PCV13, give 1 dose of PCV13.e
23PPV
(Pneumovax 23)

Following the completion of the PCV13 course, give 1 dose of 23PPV at age ≥2 years. There must be at least 8 weeks between the last PCV13 dose and the 23PPV dose.

Revaccinate once with 23PPV, 5 years after the 1st 23PPV.

MenCCV
(NeisVac-C) and

MCV4-D
(Menactra)

If aged 12–23 months at diagnosis, give 1 dose of MenCCV, followed by MCV4‑Db at age 2 years, 2 doses 8 weeks apart; then a booster of MCV4-D after 3 years, then 5‑yearly.

If aged ≥2 years at diagnosis, give 2 doses of MCV4-Db 8 weeks apart, and:

  • if the 1st MCV4-D dose was given at age <7 years, give a booster after 3 years, then 5‑yearly, or
  • if the 1st MCV4-D dose was given at age ≥7 years, give a booster dose every 5 years.
Hib
(Hiberix)

If aged 12–15 months, give 1 dose at age 15 months as per the National Immunisation Schedule.f

If aged 16 months to under 5 years and has not received a single Hib dose after age 12 months, give 1 dose.f

If aged 5 years and older, give 1 dose, even if fully vaccinated.f

Influenza
(Influvac)
Annual immunisation.c In previously unimmunised children aged under 9 years, give 2 doses 4 weeks apart, then 1 dose in each subsequent year.
Varicella
(Varilrix)

Give 1 dose at age 15 months, as per the National Immunisation Schedule.g,h

If no history of varicella disease or immunisation, give 1 dose at age 11 years.i

Varicella
(Varilrix or Varivax)

For susceptible children who do not meet the eligibility criteria for funded vaccine:

  • if aged under 13 years, give 1 doseh
  • if aged 13 years and older, give 2 doses, at least 6 weeks apart.
Aged ≥18 years when diagnosed with functional asplenia or pre-a or post-splenectomy PCV13
(Prevenar 13)
1 dose of PCV13.j
23PPV
(Pneumovax 23)
Give a maximum of 3 doses of 23PPV in a lifetime, a minimum of 5 years apart. The 1st 23PPV dose is given at least 8 weeks after PCV13; the 2nd a minimum of 5 years later; the 3rd dose at age ≥65 years.
MCV4-D
(Menactra)
Give 2 doses of MCV4-D, 8 weeks apart, then 1 dose every 5 years.b,k
Hib
(Hiberix)
Give 1 dose of Hib, regardless of previous vaccination history.
Tdap (Boostrix) Give 3 doses of Tdapl 4 weeks apart.
Influenza (Influvac) Annual immunisation.c
Varicella
(Varilrix or Varivax)
If no history of varicella disease or immunisation, give 2 doses, at least 6 weeks apart.
  1. Where possible, the vaccines should be administered at least 2 weeks before elective splenectomy. For emergency splenectomy, the vaccines should be administered 2 weeks post-operatively.
  2. Give MCV4-D at least 4 weeks after PCV1312, 13 (see section 12.4.4).
  3. Influenza vaccine is recommended but not funded for individuals with functional asplenia.
  4. If 23PPV has already been given (prior to any doses of PCV13) to children aged under 18 years, wait at least 8 weeks before administering PCV13.
  5. There are no safety concerns, regardless of the interval between the last dose of PCV10 and the 1st dose of PCV13.
  6. Hib is not required if the child is being revaccinated with DTaP-IPV-HepB/Hib.
  7. Funded for children who were born on or after 1 April 2016.
  8. A second VV dose is not currently funded but may be purchased for those who wish to reduce the risk of breakthrough disease.
  9. Funded for previously unvaccinated children who are turning 11 years old on or after 1 July 2017 who have not previously had a varicella infection.
  10. If 23PPV has already been given (prior to any doses of PCV13) to adults aged 18 years and older, wait at least 1 year before administering PCV13.
  11. MCV4-D is registered for individuals aged 9 months to 55 years, but there are not expected to be any safety concerns when administered to adults older than 55 years.
  12. Although Tdap is not registered for use as a primary course, there are expected to be to be no safety concerns.

Source: Starship Children’s Health.

4.3.5 Other high-risk individuals

Individuals with chronic lung diseases should receive influenza and pneumococcal vaccines. See chapters 10 and 15.

4.3.6 (Re-)vaccination following immunosuppression

All vaccines on the National Immunisation Schedule are funded for (re‑)vaccination of individuals following immunosuppression. Note that the period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days. The timing and number of doses should be discussed with the individual’s specialist.

See also the individual disease chapters.

4.4 Immigrants and refugees

4.4.1 Introduction

Adults and children who enter New Zealand as refugees or immigrants will need an assessment of their documented vaccination status and an appropriate catch-up programme planned.

Regardless of their immigration and citizenship status, all children aged under 18 years are eligible to receive Schedule vaccines, and providers can claim the immunisation benefit for administering the vaccines (see the ‘Eligibility for publicly funded vaccines’ section in the Introduction to this Handbook). All children are also eligible for Well Child Tamariki Ora services, regardless of immigration and citizenship status. For more information about eligibility for publicly funded services, see the Ministry of Health website (www.health.govt.nz/eligibility).

Children who have been previously immunised in low-income country may have received BCG, three doses of DTwP and oral polio vaccine (and/or IPV) in the first six months of life, and a dose of measles vaccine between 9 and 15 months of age. However, they are unlikely to have received Hib, pneumococcal, HepB, MMR or VV. Many countries, including European countries, do not have HepB included in their national childhood immunisation schedule. For immigrant children a catch-up immunisation plan may be needed.

If a refugee or immigrant has no valid documentation of vaccination, an age-appropriate catch-up programme is recommended (see Appendix 2). The programme may require modification for any documented doses: only clearly documented doses should be considered as given.

Details of immunisation schedules of other countries can be found on the WHO website (http://apps.who.int/immunization_monitoring/ globalsummary/schedules). See also the Recommendations for Comprehensive Post-Arrival Health Assessment for People from Refugee-like Backgrounds (2016 edition), available on the Australasian Society for Infectious Diseases website (www.asid.net.au/resources/clinical-guidelines).

4.4.2 Tuberculosis

TB is an important public health problem for refugees and immigrants. Figures from the US show that approximately 1–2 percent of refugees are suffering from active TB on arrival, and about half have positive tuberculin skin tests. The number who have received BCG immunisation is unknown. In New Zealand there is a significant increasing trend in the number of TB cases in overseas-born people.

Suspected TB must be appropriately investigated. If individuals are known to have been recently exposed but tests are negative, they should be tested again three months later to identify recently acquired infection. Previous BCG immunisation should be considered when interpreting tuberculin skin test results (see chapter 20).

In New Zealand, the policy is to offer BCG vaccination to infants at increased risk of TB who:

4.4.3 Hepatitis B

If a member of an immigrant or refugee family is found to have chronic HBV infection, it is recommended that all the family be screened and immunisation offered to all those who are non-immune. Even if no one in the family has chronic HBV infection, it is recommended that all children aged under 18 years be vaccinated against hepatitis B. See chapter 8 for more information and Appendix 2 for catch-up schedules.

4.4.4 Varicella

People who have grown up in the tropics are less likely to have had chickenpox and may be non-immune adolescents and adults. Because adult chickenpox can be severe, if there is no history of chickenpox, VV should be offered (although it is currently not funded).

4.5 Travel

All travellers should be encouraged to consider vaccination requirements well in advance of overseas travel. For example, information on diphtheria, MMR, influenza and hepatitis A vaccination for adults is included in the appropriate sections of this Handbook. Up‑to-date information on overseas travel requirements (eg, for typhoid, yellow fever, rabies, Japanese encephalitis) can be obtained from the Centers for Disease Control and Prevention (wwwnc.cdc.gov/travel) or the WHO (www.who.int/ith/en/).

4.6 Occupational and other risk factors

Certain occupations result in increased risk of contracting some vaccine-preventable diseases. Some infected workers, particularly health care workers and those working in early childhood education services, may transmit infections such as influenza, rubella, measles, mumps, varicella and pertussis to susceptible contacts, with the potential for serious outcomes.

Where workers are at significant occupational risk of acquiring a vaccine-preventable disease, the employer should implement a comprehensive occupational immunisation programme, including immunisation policies, staff immunisation records, information about the relevant vaccine-preventable diseases and the management of vaccine refusal. Employers should take all reasonable steps to encourage susceptible workers to be immunised.

The vaccines in Table 4.8 are recommended for certain occupational groups and in Table 4.9 for those with other risk factors. In addition to the vaccines listed below, all adults should be up to date with routinely recommended vaccines, such as MMR (see section 2.1.7 or Appendix 2).

If a non-immune individual is exposed to a vaccine-preventable disease, post-exposure prophylaxis and control measures should be administered where indicated (see the relevant disease chapters and the Communicable Disease Control Manual 201225).

Table 4.8: Recommended vaccines, by occupational group
Occupation Recommended vaccines
Health care workers
Medical, nursing, lead maternity carers, other health professional staff and students

Hepatitis B (if susceptible)

MMR (if susceptible)

Influenza, annually

Varicella (if susceptible)

Hepatitis A (if work with children)

Tetanus, diphtheria and pertussis (Tdap) (if work with children)

Individuals who work with children
Early childhood education services staff

Hepatitis A

Hepatitis B (if susceptible)

MMR (if susceptible)

Influenza, annually

Varicella (if susceptible)

Tdap

Other individuals working with children, including:

  • correctional staff working where infants/children live with mothers
  • school teachers (including student teachers)
  • outside school hours carers
  • child counselling services workers
  • youth services workers

Influenza, annually

MMR (if susceptible)

Tdap

Varicella (if susceptible)

Carers
Health care assistants, long-term facility carers, nursing home staff

Hepatitis A (if exposed to faeces)

Hepatitis B (if susceptible)

Influenza, annually

MMR (if susceptible)

Tdap

Varicella (if susceptible)

Emergency and essential service workers
Police and emergency workers

Hepatitis B (if susceptible)

Influenza, annually

Tetanus (Td or Tdap)

Armed forces personnel

Hepatitis B (if susceptible)

Influenza, annually

MMR (if susceptible)

Tetanus (Td or Tdap)

Hepatitis A (if deployed to high-risk countries)

Meningococcal C conjugate or quadrivalent meningococcal conjugate (if living in close quarters)

Quadrivalent meningococcal conjugate, yellow fever, rabies, typhoid, Japanese encephalitis (as appropriate, if deployed to high-risk countries)

Staff of correctional facilities

Hepatitis B (if susceptible)

Influenza, annually

MMR (if susceptible)

Staff of immigration/refugee centres

Hepatitis B (if susceptible)

Influenza, annually

MMR (if susceptible)

Laboratory staff
Laboratory staff

Hepatitis B (if susceptible)

MMR (if susceptible)

Influenza, annually

Hepatitis A (if exposed to faeces)

IPV

Laboratory staff regularly working with Neisseria meningitidis Quadrivalent meningococcal conjugate vaccine
Individuals who work with animals
Veterinarians, veterinary students, veterinary nurses

Influenza, annually

BCG (if exposed to infected animals)

Zoo staff who work with primates

Hepatitis A

Influenza, annually

Poultry workers and others handling poultry, including those who may be involved in culling during an outbreak of avian influenza, and swine industry workers Influenza, annually
Other individuals exposed to human tissue, blood, body fluids or sewage
Workers who perform skin penetration procedures (eg, tattooists, body-piercers) Hepatitis B (if susceptible)
Funeral workers, embalmers and other workers who have regular contact with human tissue, blood or body fluids and/or used needles or syringes Hepatitis B (if susceptible)
Sewage workers, plumbers or other workers in regular contact with untreated sewage

IPV

Hepatitis A

Sex workers

Hepatitis B (if susceptible)

HPV

Table 4.9: Recommended vaccines for those with other risk factors
Risk factor Recommended vaccines
Individuals living in hostels or other close quarters (eg, university hostels, boarding schools)

Hepatitis B (if susceptible)

MMR (if susceptible)

Influenza, annually

Meningococcal C conjugate or quadrivalent meningococcal conjugate*

Individuals in correctional facilities

Hepatitis B (if susceptible)

MMR (if susceptible)

Influenza, annually

Meningococcal C conjugate

Men who have sex with men

Hepatitis B (if susceptible)

Hepatitis A

HPV

Intravenous drug users

Hepatitis B (if susceptible)

Hepatitis A

Influenza, annually

*     Quadrivalent meningococcal conjugate vaccine is recommended if future travel is likely.

References

  1. Eick AA, Uyeki TM, Klimov A, et al. 2011. Maternal influenza vaccination and effect on influenza virus infection in young infants. Archives of Pediatrics and Adolescent Medicine 165(2): 104–11.
  2. Marshall H, McMillan M, Andrews RM et al. 2016. Vaccines in pregnancy: the dual benefit for pregnant women and infants. Human Vaccines & Immunotherapeutics 12(4): 848–56. DOI: 10.1080/21645515.2015.1127485 (accessed 24 September 2016).
  3. Zaman K, Roy E, Arifeen SE, et al. 2008. Effectiveness of maternal influenza immunization in mothers and infants. New England Journal of Medicine 359(15): 1555–64.
  4. Esposito S, Tagliabue C, Tagliaferri L, et al. 2012. Preventing influenza in younger children. Clinical Microbiology and Infection 18(Suppl 5): 42–9.
  5. Tamma PD, Ault KA, del Rio C, et al. 2009. Safety of influenza vaccination during pregnancy. American Journal of Obstetrics and Gynecology 201(6): 547–52.
  6. Regan A, Moore HC, de Klerk N, et al. 2016. Seasonal trivalent influenza vaccination during pregnancy and the incidence of stillbirth: population-based retrospective cohort study. Clinical Infectious Diseases 62(10): 1221–7. DOI: 10.1093/cid/ciw082 (accessed 17 November 2016).
  7. Bednarczyk RA, Adjaye‐Gbewonyo D, Omer SB. 2012. Safety of influenza immunization during pregnancy for the fetus and the neonate. American Journal of Obstetrics and Gynecology 207(3 Suppl): 38–46.
  8. Amirthalingam G, Andrews N, Campbell H, et al. 2014. Effectiveness of maternal pertussis vaccination in England: an observational study. The Lancet 384(9953): 1521–8. DOI: http://dx.doi.org/10.1016/S0140-6736(14)60686-3 (accessed 10 August 2015).
  9. Donegan K, King B, Bryan P. 2014. Safety of pertussis vaccination in pregnant women in the UK: observational study. British Medical Journal 349(11 July): g4219. DOI: 10.1136/bmj.g4219 (accessed 10 August 2014).
  10. Department of Health and Ageing. 2016. Rotavirus. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-17 (accessed 29 September 2016).
  11. Lee J, Robinson JL, Spady DW. 2006. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatrics 20(6): 20. DOI: 10.1186/1471-2431-6-20 (accessed 11 October 2013).
  12. Centers for Disease Control and Prevention. 2013. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports 62(2): 1–28. URL: www.cdc.gov/mmwr/pdf/rr/rr6202.pdf (accessed 27 September 2013).
  13. Pina LM, Bassily E, Machmer A, et al. 2012. Safety and immunogenicity of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants and toddlers: three multicenter phase III studies. Pediatric Infectious Disease Journal 31(11): 1173–83.
  14. Bakare N, Menschik D, Tiernan R, et al. 2010. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine 28(40): 6609–12. DOI: 10.1016/j.vaccine.2010.07.039 (accessed 23 December 2016).
  15. Morillo-Gutierrez B, Worth A, Valappil M, et al. 2015. Chronic infection with rotavirus vaccine strains in UK children with severe combined immunodeficiency. Pediatric Infectious Disease Journal 34(9): 1040–1. DOI: 10.1097/INF.0000000000000788 (accessed 23 December 2016).
  16. Klinkenberg D, Blohn M, Hoehne M, et al. 2015. Risk of rotavirus vaccination for children with SCID. Pediatric Infectious Disease Journal 34(1): 114–15. DOI: 10.1097/INF.0000000000000507 (accessed 23 December 2016).
  17. Østensen M. 2014. Safety issues of biologics in pregnant patients with rheumatic diseases. Annals of the New York Academy of Sciences 1317(1): 32–8. DOI: 10.1111/nyas.12456 (accessed 20 December 2016).
  18. Cheent K, Nolan J, Shariq S, et al. 2010. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. Journal of Crohn’s and Colitis 4(5): 603–5.
  19. American Academy of Pediatrics. 2015. Immunization in special clinical circumstances – immunization in immunocompromised children. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  20. Rubin LG, Levin MJ, Ljungman P, et al. 2013. 2013 IDSA Clinical Practice Guideline for vaccination of the immunocompromised host. Clinical Infectious Diseases 58(3): e44–e100. DOI: 10.1093/cid/cit684 (accessed 5 December 2013).
  21. Department of Health and Ageing. 2016. Vaccination for special risk groups. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part3 (accessed 1 September 2016).
  22. Gedalia A, Shetty AK. 2004. Chronic steroid and immunosuppressant therapy in children. Pediatrics in Review 25(12): 425–34.
  23. Neuhaus TJ. 2004. Immunization in children with chronic renal failure: a practical approach. Pediatric Nephrology 19(12): 1334–9.
  24. Gipson DS, Massengill SF, Yao L, et al. 2009. Management of childhood onset nephrotic syndrome. Pediatrics 124(2): 747–57.
  25. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).

5 Diphtheria

In this chapter:

Key information

5.1 Bacteriology

5.2 Clinical features

5.3 Epidemiology

5.4 Vaccines

5.5 Recommended immunisation schedule

5.6 Contraindications and precautions

5.7 Expected responses and AEFIs

5.8 Public health measures

5.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission Contact with respiratory droplets or infected skin of a case or carrier or, more rarely, contaminated articles.
Incubation period Usually 2–5 days, occasionally longer.
Period of communicability Variable; usually 2 weeks or less, seldom more than 4 weeks. Carriers may shed for longer. Effective antimicrobial therapy promptly terminates shedding.
Funded vaccines

DTaP-IPV-HepB/Hib (Infanrix-hexa).

DTaP-IPV (Infanrix-IPV).

Tdap (Boostrix).

Td (ADT Booster).

Dose, presentation, route

0.5 mL per dose.

DTaP-IPV-HepB/Hib: pre-filled syringe and glass vial. The vaccine must be reconstituted prior to injection.

DTaP-IPV, Tdap, Td: pre-filled syringe.

Intramuscular injection.

Funded vaccine indications and schedule

6 weeks, 3 months and 5 months: DTaP-IPV-HepB/Hib.

4 years: DTaP-IPV.

11 years: Tdap.

45 and 65 years: Td (administration not funded).

During pregnancy (from 28 to 38 weeks’ gestation): Tdap.

For (re-)vaccination of eligible patients: DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap or Td.

For testing for primary immune deficiencies: Td.

Dose interval between Td and Tdap No minimum interval is required between Td and Tdap, unless Tdap is being given as part of a primary immunisation course.
Vaccine efficacy/ effectiveness 87–98 percent protection has been demonstrated using population-based analysis. Immunised cases have been shown to have less severe disease.
Herd immunity ≥70 percent of the childhood population must be immune to diphtheria to prevent major community outbreaks.

5.1 Bacteriology

Diphtheria is a serious, often fatal, toxin-mediated disease caused by Corynebacterium diphtheriae, a non-sporulating, non-encapsulated, gram-positive bacillus. Rarely, it may also be caused by other toxin-carrying Corynebacteria species, such as Corynebacterium ulcerans.

5.2 Clinical features

Classic diphtheria characteristically involves membranous inflammation of the upper respiratory tract, with involvement of other tissues, especially the myocardium and peripheral nerves. The organism itself is rarely invasive, but a potent exotoxin produced by some strains (toxigenic strains) causes tissue damage through local and systemic actions. There is also a cutaneous form of diphtheria, which is typically less severe. The detection of either C. diphtheriae or C. ulcerans is notifiable to the medical officer of health, and the isolates should be referred to the Institute of Environmental Science and Research (ESR) for toxin detection. Transmission is by respiratory tract droplets, or by direct contact with skin lesions or contaminated articles. Cutaneous toxigenic diphtheria is more efficiently transmitted than respiratory toxigenic diphtheria.1, 2 Humans are the only known host for diphtheria, and the disease is usually spread by close personal contact with a case or carrier, or occasionally by fomites or food. The disease remains communicable for up to four weeks after infection, but carriers of C. diphtheriae may continue to shed the organism and be a source of infection for much longer.

Diphtheria has a gradual onset after an incubation period of two to five days. Symptoms and signs may be mild at first, but progress over one to two days with the development of a mildly painful tonsillitis or pharyngitis with an associated greyish membrane. Diphtheria should be suspected particularly if the membrane extends to the uvula and soft palate. The nasopharynx may also be obstructed by a greyish membrane, which leaves a bleeding area if disturbed. The breath of a patient with diphtheria has a characteristic mousy smell.

The major complication of diphtheria is respiratory obstruction, although the majority of deaths are due to the effects of diphtheria toxin on various organs. Of particular importance are the effects of the toxin on the myocardium (leading to myocarditis and heart failure), peripheral nerves (resulting in demyelination and paralysis), and the kidneys (resulting in tubular necrosis). The neuropathy begins two to eight weeks after disease onset, while the myocarditis can be early or late.

5.3 Epidemiology

5.3.1 Global burden of disease

In the pre-immunisation era diphtheria was predominantly a disease of children aged under 15 years; most adults acquired immunity without experiencing clinical diphtheria. Asymptomatic carriage was common (3–5 percent) and important in perpetuating both endemic and epidemic diphtheria. The global incidence of diphtheria dropped dramatically during the 20th century. Immunisation played a large part, but may not be wholly responsible for this reduction (see Figure 5.1). The estimated total number of diphtheria cases globally has fallen from just under 100,000 cases in 1980 to 4,530 cases in 2015.3 Approximately half of the diphtheria cases in 2015 occurred in India.4

Figure 5.1: Diphtheria global annual reported cases and DTP3* immunisation coverage, 1980–2015
Figure 5.1: Diphtheria global annual reported cases and DTP3* immunisation coverage, 1980–2015

*     DTP3 refers to the third dose of diphtheria, tetanus and pertussis vaccine.

Source: World Health Organization. Immunization, Vaccines and Biologicals: Monitoring and surveillance – Data, statistics and graphs. URL: http://www.who.int/immunization/monitoring_surveillance/data/en/ (accessed 13 February 2017).

Immunisation leads to the disappearance of toxigenic strains, but a bacteriophage containing the diphtheria toxin gene can infect and rapidly confer toxigenicity to non-toxigenic strains. This makes the return of epidemic diphtheria a real threat when there is insufficient herd immunity, as happened in the states of the former Soviet Union during 1990–97. Factors contributing to this epidemic included a large population of susceptible adults, decreased childhood immunisation, suboptimal socioeconomic conditions and high population movement.5 Diphtheria remains endemic in these countries, as well as in countries in Asia and the South Pacific, including Afghanistan, Bangladesh, Cambodia, China, India, Indonesia, Malaysia, Nepal, Pakistan, Papua New Guinea, the Philippines, Thailand, Vietnam and the Pacific Islands.6, 7

Diphtheria is rare in high-income countries such as New Zealand due to active immunisation with diphtheria toxoid-containing vaccine.

However, continuing endemic cutaneous diphtheria in indigenous communities has been reported from the US, Canada and Australia. Small diphtheria outbreaks still occur in high-income countries.8 These often appear to be caused by unvaccinated or partially vaccinated individuals travelling to endemic countries.

The overall case fatality rate for clinical diphtheria is 5–10 percent, with higher death rates (up to 20 percent) among persons younger than 5 and older than age 40 years. The case-fatality rate for diphtheria has changed very little during the last 50 years.9

5.3.2 New Zealand epidemiology

Diphtheria infection was common in New Zealand until the 1960s. The last case of toxigenic respiratory diphtheria was reported in 1998.10 Low numbers of cutaneous toxigenic diphtheria are regularly notified in New Zealand: two confirmed cases were notified in 2015 in refugees from Afghanistan, and two cases were notified in 2014.11 These cases required large-scale public health responses to identify, prophylax and vaccinate local contacts.7

Travel to endemic countries is an important risk factor for infection, but transmission within New Zealand can occur to susceptible contacts of cutaneous cases. Tattooing practices in the Pacific Islands have also been implicated in outbreaks in New Zealand.12

The 2005–2007 National Serosurvey of Vaccine Preventable Diseases found that 61 percent of 6–10-year-olds, 77 percent of 11–15-year-olds, 71 percent of 16–24-year-olds, 48 percent of 25–44-year-olds and 46 percent of ≥45-year-olds had presumed protective levels of diphtheria antibody.13 The decline apparent with age suggests there is likely to be a large and increasing pool of adults who may be susceptible to diphtheria in New Zealand, despite the introduction of adult tetanus and diphtheria (Td) vaccination in 1994.

5.4 Vaccines

Diphtheria toxoid is prepared from cell-free purified diphtheria toxin treated with formaldehyde. It is a relatively poor immunogen, which, to improve its efficacy, is usually adsorbed onto an adjuvant, either aluminium phosphate or aluminium hydroxide.

Diphtheria toxoid is only available as a component of combination vaccines (in New Zealand as DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap and Td).

See Appendix 1 for the history of diphtheria toxoid-containing vaccines in New Zealand.

5.4.1 Available vaccines

Funded diphtheria vaccines

The diphtheria toxoid-containing vaccines funded as part of the Schedule are as follows.

Other vaccines

Other diphtheria toxoid-containing vaccines registered (approved for use) and available (marketed) in New Zealand are:

5.4.2 Efficacy and effectiveness

Immunity against diphtheria occurs via an antibody‐mediated response to the diphtheria toxin and is primarily of the IgG type. Antitoxin antibodies can pass through the placenta to provide passive immunity to the newborn.

Although there are no randomised controlled studies on the efficacy of the vaccine, between 87 and 98 percent protection has been demonstrated using population-based analyses. Immunised cases have been shown to have less severe disease, as highlighted during the outbreak in the former Soviet Union.

Vaccines combining pertussis antigens with diphtheria and tetanus toxoids have been gradually introduced into immunisation schedules throughout the world. Immunogenicity data for these combination vaccines is discussed in section 14.4.2.

Herd immunity

Although immunisation is more effective at preventing disease than preventing infection, it does create herd immunity via reducing carriage and therefore transmission.14 To prevent major community outbreaks, it has been suggested that 70 percent or more of the childhood population must be immune to diphtheria.15, 16 This may explain the control of diphtheria in New Zealand despite historically relatively poor coverage.

Duration of immunity

Diphtheria antitoxin levels decline over time in children after they have received a primary series of vaccines and a booster dose is required. In countries where diphtheria immunisation is common practice and high coverage rates are achieved, there will be no natural boosting from circulating disease, and antitoxin levels declining with increasing age may result in a susceptible adult population.17

Despite this, there has been minimal disease in high-income countries, suggesting that antibody levels may not be a reliable guide to protection and that other factors may be operating.18 For example, a high proportion of the adult German population have low antibody levels, indicating susceptibility, yet this has not led to diphtheria outbreaks despite Germany’s relative geographical proximity to the former Soviet Union.19

The duration of protection after Tdap boosters is unknown, but the results of an Australian study have shown that five years after the Tdap booster dose, 94.4 percent of adults had seroprotective levels of antibodies against diphtheria, compared with 93.7 percent who received Td vaccine.20

5.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.21 Store at +2°C to +8°C. Do not freeze.

DTaP-IPV-HepB/Hib and Td should be stored in the dark.

5.4.4 Dosage and administration

The dose of DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap or Td vaccine is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

Co-administration with other vaccines

DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap or Td vaccine can be administered simultaneously (at separate sites) with other vaccines or IGs.

5.5 Recommended immunisation schedule

Table 5.1: Immunisation schedule for diphtheria-containing vaccines (excluding catch-up)
Age Vaccine Comment
6 weeks DTaP-IPV-HepB/Hib Primary series
3 months DTaP-IPV-HepB/Hib Primary series
5 months DTaP-IPV-HepB/Hib Primary series
4 years DTaP-IPV Booster
11 years Tdap Booster
45 years Tda Booster
65 years Tda Booster
Pregnant women (weeks 28–38 of each pregnancy) Tdap Boosterb
  1. The Td vaccine is funded at ages 45 and 65 years, but not the administration.
  2. The Tdap booster during pregnancy is for protection against pertussis (see section 4.1.2).

5.5.1 Usual childhood schedule

A primary course of diphtheria vaccine is given as DTaP-IPV-HepB/Hib (Infanrix-hexa) at ages 6 weeks, 3 months and 5 months, followed by a dose of DTaP-IPV (Infanrix-IPV) at age 4 years (Table 5.1). A booster is given at age 11 years (school year 7), which includes a pertussis component given as the vaccine Tdap (Boostrix).

If a course of immunisation is late or interrupted for any reason, it may be resumed without repeating prior doses (see Appendix 2).

Alternatives to pertussis-containing vaccines

Some parents or guardians may ask about alternatives to pertussis-containing vaccines. The recommended and funded vaccines for children are those described above. There are no diphtheria-only or tetanus-only vaccines available. The Td vaccine contains half the amount of tetanus toxoid and one-fifteenth the amount of diphtheria toxoid compared to the DTaP-containing vaccines. Td was not clinically designed or tested for use to provide the primary vaccine course in children and it is not registered for use in children aged under 5 years. Although there are no safety concerns relating to administration of the vaccine, there is no data on the use of this vaccine for a primary course in children and it is not recommended.

5.5.2 Catch-ups for individuals aged 10 years and older

For previously unimmunised individuals aged 10 years and older, a primary immunisation course consists of three doses of a diphtheria toxoid-containing vaccine at intervals of not less than four weeks (see Appendix 2). For children aged under 18 years, a booster dose is recommended at least six months after the third dose.

Children aged under 18 years may receive Tdap (funded from age 7 to under 18 years); adults aged 18 years and older may receive Td (funded) or Tdap (unfunded). Although Tdap and Td are not approved for use (registered) as a primary course, there are expected to be no safety concerns.

Dose intervals between Td and Tdap

When Tdap is to be given to adolescents or adults to protect infants or other vulnerable individuals from pertussis, no minimum interval between Td and Tdap is required22, 23, 24 – unless Tdap is being given as part of a primary immunisation course.

5.5.3 Booster doses for adults

Studies overseas show that many adults lack protective levels of the antibody, and this has led to concern about waning immunity and recommendations for booster doses beyond childhood (see also section 5.3.2). Most authorities recommend maintaining diphtheria immunity by periodic reinforcement using Td.8 A single booster dose of Tdap induces seroprotective levels of antibodies to diphtheria and tetanus in virtually all children and adolescents, and in a high proportion of adults and elderly individuals at approximately one month post‐vaccination, irrespective of their vaccination history.25

In New Zealand, following the dose of Tdap at age 11 years, booster doses of Td are recommended (the vaccine is funded, but not the administration) at ages 45 and 65 years. These age-specific recommendations may facilitate the linkage of adult immunisation to the delivery of other preventive health measures.

Booster doses before travel

If someone is travelling to an area endemic for diphtheria, or there is another reason to ensure immunity, a booster dose is recommended (but not funded) if it is more than 10 years since the last dose. For website sources on travel vaccines, see Appendix 9.

5.5.4 Pregnancy and breastfeeding

Pregnant women should receive a dose of Tdap (funded) from 28 to 38 weeks’ gestation. This should be given during each pregnancy26 to protect the mother against pertussis and so that antibodies can pass to the fetus to protect the newborn (see section 4.1.2).

Td vaccine is not routinely recommended for pregnant women but it can be given under certain circumstances, such as when catch-up is needed for an under-immunised woman, or for management of a tetanus-prone wound26, 27 (see section 19.5.5).

Td or Tdap vaccines can be given to breastfeeding women.27

5.5.5 (Re-)vaccination

Diphtheria toxoid-containing vaccines are funded for (re-)vaccination of eligible patients, as follows. See also sections 4.2 and 4.3.

DTaP-IPV-HepB/Hib (Infanrix-hexa) and DTaP-IPV (Infanrix-IPV)

An additional four doses (as appropriate) of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for (re‑)vaccination of patients:

Up to five doses of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for children requiring solid organ transplantation.

Tdap (Boostrix)

An additional four doses (as appropriate) of Tdap (Boostrix) are funded for patients:

Td (ADT Booster)

Td is funded for patients following immunosuppression.

5.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

5.6.1 Contraindications

There are no specific contraindications to diphtheria vaccine (or Td/DT), except for anaphylaxis to a previous dose or any component of the vaccine.

5.6.2 Precautions

See section 14.6.2 for precautions for pertussis-containing vaccines.

5.7 Expected responses and AEFIs

Despite the widespread use of diphtheria toxoid, the 1994 Institute of Medicine review of vaccine reactions did not identify any reaction for which the evidence favoured or established a causal relationship with diphtheria toxoid.28 However, local and systemic reactions do occur with diphtheria toxoid-containing vaccine, especially when the infant vaccine is used in older children and adults. Mild discomfort or pain at the injection site persisting for up to a few days is common.29

See also sections 14.7 and 19.7 for expected responses and AEFIs with DTaP-IPV-HepB/Hib, DTaP-IPV, Tdap and Td.

5.8 Public health measures

Alert the laboratory that the sample is from a suspected case of diphtheria. All isolates of C. diphtheriae and C. ulcerans are notifiable until toxigenicity is determined, including cutaneous isolates. If the isolate is determined to be nontoxigenic (does not have the ability to produce diphtheria toxin), the case should be denotified.

All patients with C. diphtheriae or C. ulcerans isolated from a clinical specimen should be discussed with the medical officer of health urgently.

All contacts should have cultures taken.

5.8.1 Antimicrobial prophylaxis

All close contacts, after cultures have been taken and regardless of immunisation status, should receive:

Benzathine penicillin is preferred for contacts who cannot be kept under surveillance.

In contacts with a positive culture: two follow-up cultures should be obtained at least 24 hours after completion of therapy. If cultures are still positive, discuss further management with an infectious diseases physician. The primary healthcare practitioner should be kept informed of the management of contacts and laboratory results.

5.8.2 Vaccination of contacts

All close contacts should also be offered a complete course of vaccine or a booster according to the following schedule.

5.8.3 Exclusion of contacts

Child contacts should be excluded from school, early childhood services and community gatherings until they are known to be culture negative. Adult contacts who are food handlers or who work with children should be excluded from work until known to be culture negative. Cases should be excluded from school until recovery has taken place and two negative throat swabs have been collected one day apart and one day after cessation of antibiotics.

For more details on control measures, refer to the ‘Diphtheria’ chapter of the Communicable Disease Control Manual 2012.30

5.9 Variations from the vaccine data sheets

See section 14.9 for variations from the DTaP-IPV-HepB/Hib (Infanrix-hexa), DTaP-IPV (Infanrix-IPV) and Tdap (Boostrix) data sheets.

See section 19.9 for variations from the Td (ADT Booster) data sheet.

References

  1. Koopman JS, Campbell J. 1975. The role of cutaneous diphtheria infections in a diphtheria epidemic. Journal of Infectious Diseases 131(3): 239–44. DOI: 10.1093/infdis/131.3.239 (accessed 19 December 2016).
  2. Besley MA, Sinclair TM, Roder MR. 1969. Corynebacterium diphtheriae skin infections in Alabama and Louisana: a factor in the epidemiology of diphtheria. New England Journal of Medicine 280(3): 135–41. DOI: 10.1056/NEJM196901162800304 (accessed 19 December 2016).
  3. World Health Organization. 2016. Diphtheria. URL: http://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/ (accessed 29 November 2016).
  4. World Health Organization. 2016. Diphtheria Reported Cases, 2015. URL: http://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencediphtheria.html (accessed 29 November 2016).
  5. Vitke CR, Wharton M. 1998. Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerging Infectious Diseases 4(4): 539–50. URL: https://wwwnc.cdc.gov/eid/article/4/4/98-0404_article (accessed 29 September 2013).
  6. Rahim NR, Koehler AP, Shaw DD, et al. 2014. Toxigenic cutaneous diphtheria in a returned traveller. Communicable Diseases Intelligence 38(4): E298–300.
  7. Reynolds GE, Saunders H, Matson A, et al. 2016. Public health action following an outbreak of toxigenic cutaneous diphtheria in an Auckland refugee resettlement centre. Communicable Diseases Intelligence 40(4): E475–81. URL: http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-cdi4004e.htm (accessed 24 December 2016).
  8. Tiwari TSP, Wharton M. 2013. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  9. Centers for Disease Control and Prevention. 2012. Diphtheria. In: Atkinson W, Hamborsky J, Wolfe S, et al (eds). Epidemiology and Prevention of Vaccine-Preventable Diseases (12th edition). Washington, DC: Public Health Foundation.
  10. Baker M, Taylor P, Wilson E, et al. 1998. A case of diphtheria in Auckland: implications for disease control. New Zealand Public Health Report 5(10): 73–6.
  11. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  12. Sears A, McLean M, Hingston D, et al. 2012. Cases of cutaneous diphtheria in New Zealand: implications for surveillance and management. New Zealand Medical Journal 125(1350): 64–71.
  13. Weir R, Jennings L, Young S, et al. 2009. National Serosurvey of Vaccine Preventable Diseases. URL: www.health.govt.nz/system/files/documents/publications/national-serosurvey-of-vaccine-preventable-diseases-may09.pdf (accessed 21 October 2013).
  14. Fine PEM. 1993. Herd immunity: history, theory, practice. Epidemiologic Reviews 15(2): 265–302.
  15. Smith JWG. 1969. Diphtheria and tetanus toxoids. British Medical Bulletin 25(2): 177–82.
  16. Ad-hoc Working Group. 1978. Susceptibility to diphtheria. The Lancet 311(8061): 428–30.
  17. World Health Organization. 2009. Module 2: Diphtheria – update 2009. The Immunological Basis for Immunization Series. URL: www.who.int/immunization/documents/immunological_basis_series/en/ (accessed 21 October 2013).
  18. Bowie C. 1996. Tetanus toxoid for adults – too much of a good thing. The Lancet 348(9036): 1185–6.
  19. Stark K, Barg J, Molz B, et al. 1997. Immunity against diphtheria in blood donors in East and West Berlin. The Lancet 350(9082): 932.
  20. McIntyre PB, Burgess MA, Egan A, et al. 2009. Booster vaccination of adults with reduced-antigen-content diphtheria, tetanus and pertussis vaccine: immunogenicity 5 years post-vaccination. Vaccine 27(7): 1062–6.
  21. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  22. Beytout J, Launay O, Guiso N, et al. 2009. Safety of Tdap-IPV given 1 month after Td-IPV booster in healthy young adults: a placebo controlled trial. Human Vaccines and Immunotherapeutics 5(5): 315–21.
  23. Talbot EA, Brown KH, Kirkland KB, et al. 2010. The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following previous tetanus vaccination: experience during a mass vaccination campaign of health care personnel during a respiratory illness outbreak. Vaccine 28(50): 8001–7.
  24. Centers for Disease Control and Prevention. 2011. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. Morbidity and Mortality Weekly Report 60(1): 13–15. URL: www.cdc.gov/mmwr/pdf/wk/mm6001.pdf (accessed 21 October 2013).
  25. McCormack PL. 2012. Reduced-antigen, combined diphtheria, tetanus and acellular pertussis vaccine, adsorbed (Boostrix): a review of its properties and use as a single-dose booster immunization. Drugs 72(13): 1765–91.
  26. Centers for Disease Control and Prevention. 2013. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women – Advisory Committee on Immunization Practices (ACIP), 2012. Morbidity and Mortality Weekly Report 62(7): 131–5. URL: www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a4.htm (accessed 22 October 2013).
  27. Department of Health and Ageing. 2016. Tetanus. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-19 (accessed 29 November 2016).
  28. Stratton KR, Howe CJ, Johnston RB. 1994. Adverse events associated with childhood vaccines other than pertussis and rubella. Journal of the American Medical Association 271(20): 1602–5.
  29. Department of Health and Ageing. 2016. Diphtheria. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-2 (accessed 29 November 2016).
  30. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).

6 Haemophilus influenzae type b (Hib) disease

In this chapter:

Key information

6.1 Bacteriology

6.2 Clinical features

6.3 Epidemiology

6.4 Vaccines

6.5 Recommended immunisation schedule

6.6 Contraindications and precautions

6.7 Expected responses and AEFIs

6.8 Public health measures

6.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission By inhalation of respiratory tract droplets or by direct contact with respiratory tract secretions.
Incubation period Unknown, but probably 2–4 days.
Period of communicability May be prolonged. Non-communicable within
24–48 hours after starting effective antimicrobial therapy.
Disease burden Children aged under 5 years, particularly those aged under 1 year: meningitis, epiglottitis, pneumonia and bacteraemia.
Funded vaccines

DTaP-IPV-HepB/Hib (Infanrix-hexa).

Hib-PRP-T (Hiberix).

Dose, presentation, route

DTaP-IPV-HepB/Hib and Hib-PRP-T:

  • 0.5 mL per dose after reconstitution
  • pre-filled syringe and glass vial – the vaccines must be reconstituted prior to injection
  • intramuscular injection.
Funded vaccine indications and schedule

Usual childhood schedule:

  • at ages 6 weeks, 3 months and 5 months:
    DTaP-IPV-HepB/Hib
  • at age 15 months: Hib-PRP-T.

For (re-)vaccination of eligible patients:

  • up to 4 additional doses of DTaP-IPV-HepB/Hib (for eligible children <10 years); or
  • 1 additional dose of Hib-PRP-T.

For children <10 years receiving solid organ transplantation: up to 5 doses of DTaP-IPV-HepB/Hib.

For testing for primary immune deficiencies: Hib-PRP-T.

Vaccine efficacy/ effectiveness Hib disease has been almost eliminated in countries where Hib vaccine is used.
Public health measures

Rifampicin prophylaxis should be administered to contacts as appropriate.

All contacts should have their immunisation status assessed and updated as appropriate.

6.1 Bacteriology

Haemophilus influenzae is a gram-negative coccobacillus, which occurs in typeable and non-typeable (NTHi) forms. There are six antigenically distinct capsular types (a–f), of which type b is the most important. Before the introduction of the vaccine, H. influenzae type b (Hib) caused 95 percent of H. influenzae invasive disease in infants and children.

6.2 Clinical features

Transmission is by inhalation of respiratory tract droplets or by direct contact with respiratory tract secretions. Hib causes meningitis and other focal infections (such as pneumonia, septic arthritis and cellulitis) in children, primarily those aged under 2 years, while epiglottitis was more common in children over 2 years. Invasive Hib disease was rare over the age of 5 years, but could occur in adults. In the absence of vaccination these presentations may still occur. There have always been a small number of cases of H. influenzae invasive disease in adults, and these continue to occur. The incubation period of the disease is unknown, but is probably from two to four days.

Immunisation against Hib does not protect against infections due to other H. influenzae types or NTHi strains. Non-typeable H. influenzae (NTHi) organisms usually cause non-invasive mucosal infections, such as otitis media, sinusitis and bronchitis, but can occasionally cause bloodstream infection, especially in neonates. They are frequently present (60–90 percent) in the normal upper respiratory tract flora.

Young infants (aged under 2 years) do not produce an antibody response following Hib invasive disease, so a course of Hib vaccine is recommended when they have recovered (see section 6.5.3).

Hib and NTHi strains also cause diseases (including pneumonia and septicaemia) in the elderly.

6.3 Epidemiology

6.3.1 Global burden of disease

The source of the organism is the upper respiratory tract. Immunisation with a protein conjugate vaccine reduces the frequency of asymptomatic colonisation by Hib. Before the introduction of the vaccine, Hib was the most common cause of bacterial meningitis in children. Worldwide immunisation coverage is increasing, with approximately 191 countries having fully or partially introduced Hib onto their schedules by June 2016 (98 percent of all WHO member states).1

6.3.2 New Zealand epidemiology

Hib vaccine was introduced in 1994 (see Appendix 1). In 1993, 101 children aged under 5 years had laboratory-confirmed invasive Hib disease (an age-specific rate of 36.4 per 100,000 population). By 1999 only five children in this age group had laboratory-confirmed disease (1.7 per 100,000) (Figure 6.1).

Three cases of Hib were notified in 2015, of which two were laboratory-confirmed.2 The third case met the probable case definition. All cases were children aged under 5 years, and none were vaccinated. Two of the cases lived in a communal setting and were part of an outbreak. There have been five deaths from Hib between 1997 and 2015 (ESR, 21 February 2017), the most recent was in 2012 in an adult over 70 years of age.3

Figure 6.1: Number of notifications and culture-positive cases of Haemophilus influenzae type b invasive disease, 1990–2015
Figure 6.1: Number of notifications and culture-positive cases of Haemophilus influenzae type b invasive disease, 1990–2015

Source: Ministry of Health and ESR

6.4 Vaccines

Antibodies to PRP, a component of the polysaccharide cell capsule of Hib, are protective against invasive Hib disease. To induce a T-cell dependent immune response, the PRP polysaccharide has been linked (conjugated) to a variety of protein carriers. These conjugate Hib vaccines are immunogenic and effective in young infants (see also section 1.4.3). The protein carriers used are either an outer membrane protein of Neisseria meningitidis (PRP-OMP Hib vaccine), a mutant diphtheria toxin (Hb-OC Hib vaccine) or a tetanus toxoid (PRP-T Hib vaccine).

Note that the protein conjugates used in Hib vaccines are not themselves expected to be immunogenic and do not give protection against N. meningitidis, diphtheria or tetanus.

6.4.1 Available vaccines

Funded vaccines
Other vaccines

Hib-PRP-T (Act-HIB, Sanofi) was the funded vaccine prior to the 1 July 2017 Schedule change. It contains 10 µg of purified Hib capsular polysaccharide conjugated to 18–30 µg of tetanus protein; other components (excipients) include trometamol, sucrose and sodium chloride.

6.4.2 Efficacy and effectiveness

The high efficacy and effectiveness of Hib vaccines have been clearly demonstrated by the virtual elimination of Hib disease in countries implementing the vaccine,4, 5, 6 including New Zealand. Hib vaccines are highly effective after a primary course of two or three doses.7, 8, 9 Disease following a full course of Hib vaccine is rare.

Conjugate vaccines reduce carriage in immunised children and as a result also decrease disease in unimmunised people (herd immunity). These vaccines will not protect against infection with NTHi strains of H. influenzae, and therefore do not prevent the great majority of otitis media, recurrent upper respiratory tract infections, sinusitis or bronchitis.

(See also section 14.4.2 for information about the DTaP‑IPV‑HepB/Hib vaccine.)

Duration of immunity

A primary series followed by a booster dose in the second year of life should provide sufficient antibody levels to protect against invasive Hib disease to at least the age of 5 years.10

6.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.11 Store at +2°C to +8°C. Do not freeze.

DTaP-IPV-HepB/Hib should be stored in the dark.

6.4.4 Dosage and administration

The dose of DTaP-IPV-HepB/Hib and Hib-PRP-T vaccines is 0.5 mL administered by intramuscular injection (see section 2.2.3).

Co-administration

DTaP-IPV-HepB/Hib and Hib-PRP-T vaccines can be co-administered with other routine vaccines on the Schedule, in separate syringes and at separate sites.

6.5 Recommended immunisation schedule

6.5.1 Usual childhood schedule

Hib vaccine is funded for all children aged under 5 years. Three doses of DTaP-IPV-HepB/Hib (Infanrix-hexa) vaccine are given as the primary course, with a booster of Hib-PRP-T (Hiberix) at age 15 months (see Table 6.1).

Table 6.1: Usual childhood Hib schedule (excluding catch-up)
Age Vaccine Comment
6 weeks DTaP-IPV-HepB/Hib Primary series
3 months DTaP-IPV-HepB/Hib Primary series
5 months DTaP-IPV-HepB/Hib Primary series
15 months Hib-PRP-T Booster

For children aged under 5 years who, for whatever reason, have missed out on Hib vaccine in infancy, a catch-up schedule is recommended. The total number of doses of Hib vaccine required is determined by the age at which Hib immunisation commences. Where possible, the combined available vaccines should be used, but individual immunisation schedules based on the recommended national schedule may be required for children who have missed some immunisations (see Appendix 2).

6.5.2 Special groups

Children

Because of an increased risk of infection, it is particularly important that the following groups of children, whatever their age, receive the Hib vaccine as early as possible (see also sections 4.2 and 4.3):

Recommendations for Hib vaccine for older children and adults with asplenia

Although there is no strong evidence of an increased risk of invasive Hib disease in asplenic older children and adults, many authorities recommend Hib immunisation for these individuals.12, 13 The Hib PRP-T vaccine has been shown to be immunogenic in adults.

Hib-PRP-T vaccine (Hiberix) is funded for older children and adults pre- or post-splenectomy or with functional asplenia; one dose of vaccine is recommended (see also section 4.3.4).

(Pneumococcal, meningococcal, influenza, varicella and pertussis-containing vaccines are also recommended for these individuals; see section 4.3.4 and the relevant disease chapters.)

6.5.3 Children who have recovered from invasive Hib disease

Children aged under 2 years with Hib disease do not reliably produce protective antibodies and need to receive a complete course of Hib vaccine. The number of doses required will depend on the age at which the first dose after the illness is given, ignoring any doses given before the illness (follow the age-appropriate catch-up schedules in Appendix 2).

Commence immunisation approximately four weeks after the onset of disease.

Any immunised child who develops Hib disease or who experiences recurrent episodes of Hib invasive disease requires immunological investigation by a paediatrician.

6.5.4 (Re-)vaccination

Hib-containing vaccines are funded for (re-)vaccination of eligible patients, as follows. See also sections 4.2 and 4.3.

DTaP-IPV-HepB/Hib (Infanrix-hexa)

An additional four doses (as appropriate) of DTaP-IPV-HepB/Hib are funded for (re-)vaccination of children aged under 10 years:

Up to five doses of DTaP-IPV-HepB/Hib are funded for children aged under 10 years receiving solid organ transplantation.

Hib-PRP-T (Hiberix)

One additional dose of Hib-PRP-T (Hiberix) is funded for (re‑)vaccination of patients:

6.5.5 Pregnancy and breastfeeding

Hib vaccine is not routinely recommended for pregnant or breastfeeding women. However, for asplenic women refer to ‘Recommendations for Hib vaccine for older children and adults with asplenia’ in section 6.5.2 above.

6.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general vaccine contraindications. Anaphylaxis to a previous vaccine dose or any component of the vaccine is an absolute contraindication to further vaccination with that vaccine.

See section 14.6 for contraindications and precautions to DTaP‑IPV‑HepB/Hib vaccine.

Hib-PRP-T vaccines should not be administered to people with a history of an anaphylactic reaction to a prior dose of Hib vaccine or to a vaccine component. Significant hypersensitivity reactions to Hib vaccines appear to be extremely rare.

6.7 Expected responses and AEFIs

See section 14.7.1 for expected responses and AEFIs with DTaP‑IPV‑HepB/Hib vaccine.

6.7.1 Expected responses

Adverse reactions to Hib conjugate vaccines are uncommon. Pain, redness and swelling at the injection site occur in approximately 25 percent of recipients, but these symptoms typically are mild and last less than 24 hours.14

6.7.2 AEFIs

A meta-analysis of trials of Hib vaccination from 1990 to 1997 found that serious adverse events were rare.15 No serious vaccine-related adverse experiences were observed during clinical trials of Hib vaccine alone. There have been rare reports, not proven to be causally related to Hib vaccine, of erythema multiforme, urticaria, seizures and Guillain–Barré syndrome (GBS).16

6.8 Public health measures

6.8.1 Management of contacts

All child contacts should have their immunisation status assessed and updated, as appropriate.

Immunisation reduces – but does not necessarily prevent – the acquisition and carriage of Hib. Therefore, immunised children still need rifampicin prophylaxis, when indicated, to prevent them transmitting infection to their contacts. Careful observation of exposed household and early childhood service contacts is essential. Exposed children who develop a febrile illness should receive prompt medical evaluation.

Rifampicin chemoprophylaxis

To eradicate the carrier state and protect susceptible children, antimicrobial prophylaxis should be given to contacts as soon as possible, and ideally within seven days of the index case developing the disease, irrespective of their own immunisation status. Prophylaxis started after seven days may still be of benefit and is recommended. Note that the prophylaxis for Hib is different from that for meningococcal disease (see chapter 12).

Rifampicin recommendations

Chemoprophylaxis with rifampicin is recommended for the following contacts of an index case of Hib:

Use oral rifampicin 20 mg/kg (maximum 600 mg) daily for four days. The dose for infants aged under 4 weeks has not been established, but a dose of 10 mg/kg per day is recommended. This is a different regimen to that recommended for prophylaxis from meningococcal disease (see chapter 12).

The index case should also receive rifampicin unless treated with cefotaxime or ceftriaxone.

Rifampicin is not recommended for:

For more details on control measures, refer to the ‘Haemophilus influenzae type b invasive disease (Hib)’ chapter of the Communicable Disease Control Manual 2012.17

6.9 Variations from the vaccine data sheets

The Hib-PRP-T (Hiberix) data sheet states that the vaccine is not intended for use in adults. However, the Ministry of Health recommends that asplenic adults (see section 6.5.2) or adults with specified immunocompromised conditions (see section 6.5.4) receive Hib-PRP-T vaccine.12, 13 There are not expected to be any safety concerns for use in older age groups.

See section 14.9 for variations from the DTaP-IPV-HepB/Hib (Infanrix‑hexa) data sheet.

References

  1. World Health Organization. 2016. Vaccine Introduction Slides. URL: http://www.who.int/immunization/monitoring_surveillance/data/en/ (accessed 4 August 2016).
  2. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  3. Institute of Environmental Science and Research Ltd. 2013. Notifiable and Other Diseases in New Zealand: Annual Report 2012. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2012/2012AnnualSurvRpt.pdf (accessed 19 August 2013).
  4. Ladhani SN. 2012. Two decades of experience with the Haemophilus influenzae serotype b conjugate vaccine in the United Kingdom. Clinical Therapeutics 34(2): 385–99.
  5. Bisgard KM, Kao A, Leake J, et al. 1998. Haemophilus influenzae invasive disease in the United States, 1994–1995: near disappearance of a vaccine-preventable childhood disease. Emerging Infectious Diseases
    4(2): 229–37.
  6. MacNeil JR, Cohn AC, Farley M, et al. 2011. Current epidemiology and trends in invasive Haemophilus influenzae disease – United States,
    1989–2008. Clinical Infectious Diseases 53(12): 1230–6.
  7. Griffiths UK, Clark A, Gessner B, et al. 2012. Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials. Epidemiology & Infection 140(8): 1343–55.
  8. O’Loughlin RE, Edmond K, Mangtani P, et al. 2010. Methodology and measurement of the effectiveness of Haemophilus influenzae type b vaccine: systematic review. Vaccine 28(38): 6128–36.
  9. Kalies H, Grote V, Siedler A, et al. 2008. Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany’s experience after 5 years of licensure. Vaccine 26(20): 2545–52.
  10. Khatami A, Snape MD, John TM, et al. 2011. Persistence of immunity following a booster dose of Haemophilus influenzae type B-meningococcal serogroup C glycoconjugate vaccine: follow-up of a randomized controlled trial. Pediatric Infectious Disease Journal 30(3): 197–202.
  11. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  12. Centers for Disease Control and Prevention. 2014. Prevention and control of Haemophilus influenzae type b disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports 63(RR-1): 1–14. URL: https://www.cdc.gov/mmwr/pdf/rr/rr6301.pdf (accessed 1 April 2017).
  13. Public Health England. 2016. Immunisation of individuals with underlying medical conditions. In: The Green Book. URL: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/566853/Green_Book_Chapter7.pdf (accessed 1 April 2017).
  14. American Academy of Pediatrics. 2015. Haemophilus influenzae infections. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  15. Obonyo CO, Lau J. 2006. Efficacy of Haemophilus influenzae type b vaccination of children: a meta-analysis. European Journal of Clinical Microbiology & Infectious Diseases 25(2): 90–97.
  16. Chandran A, Watt P, Santosham M. 2013. Haemophilus influenzae vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  17. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).

7 Hepatitis A

In this chapter:

Key information

7.1 Virology

7.2 Clinical features

7.3 Epidemiology

7.4 Vaccines

7.5 Recommended immunisation schedule

7.6 Contraindications and precautions

7.7 Expected responses and AEFIs

7.8 Public health measures

7.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission Faecal–oral route, either from person-to-person contact or through contaminated food or drink. It is also occasionally spread by injected drug use.
Incubation period 28–30 days average (range 15–50 days).
Period of communicability The 1–2 weeks before and the first few days after the onset of jaundice.
Burden of disease Infants and children are usually asymptomatic. Severity in adults increases with age. The disease is more serious in those with chronic liver disease and the immunocompromised. There is no carrier state.
Vaccines (registered and available)

Monovalent inactivated hepatitis A virus (HAV) vaccine (Havrix; Avaxim).

Combined inactivated HAV-recombinant HBsAg protein vaccine (Twinrix).

Combined HAV-purified Salmonella typhi Vi polysaccharide vaccine (Hepatyrix; Vivaxim).

Dose, presentation, route

Havrix, Twinrix, Hepatyrix, Vivaxim: 1.0 mL per dose.

Havrix Junior, Twinrix Junior, Avaxim: 0.5 mL per dose.

Pre-filled syringe.

Intramuscular injection.

Funded vaccine indications

HAV vaccine (Havrix) is recommended and funded for:

  • transplant patients – 2 doses
  • children with chronic liver disease – 2 doses
  • close contacts of hepatitis A cases – 1 dose.
Vaccine efficacy/ effectiveness High efficacy: HAV infection has been almost eliminated in immunised populations.
Public health measures

In an outbreak (if within 2 weeks of exposure):

  • age <12 months, human normal immunoglobulin is recommended
  • ≥12 months, age-appropriate vaccination is recommended.

7.1 Virology

Hepatitis A virus (HAV) is a ribonucleic acid (RNA) virus belonging to the picornavirus group, which also contains enteroviruses and rhinoviruses. The virus is usually transmitted by the faecal–oral route, either from person-to-person contact or through contaminated food or drink.

HAV primarily replicates in the liver and is excreted in large quantities via the biliary tract into the faeces. It is a hardy virus and can survive outside the body for prolonged periods in food and water. It causes a self-limiting illness with no carrier state.

7.2 Clinical features

The incubation period between ingestion of the virus and clinical symptoms is 15 to 50 days, with an average of 28 to 30 days. The virus can be detected in blood and faeces within a few days of ingestion, and it increases to a peak in the two weeks prior to the onset of clinical illness, which is the time that subjects are most likely to spread the infection. Faecal viral shedding continues for one to three weeks in adults, but has been reported to last longer in young children. Virus excretion falls sharply in the week following the onset of hepatitis.

In infants and preschool children, most infections are either asymptomatic or cause only mild, non-specific symptoms without jaundice. Most adults and adolescents develop symptomatic disease, the severity of which generally increases with age. Symptomatic HAV infection is characterised by an acute febrile illness with jaundice, anorexia, nausea, abdominal discomfort, malaise and dark urine. Signs and symptoms usually last less than two months, although 10–15 percent of symptomatic persons have prolonged or relapsing illness lasting up to six months. Liver enzymes almost always return to normal by six months after the illness, and often much sooner. The disease is more serious in people with chronic liver disease or those who are immunocompromised (including people with HIV infection). Chronic carrier states do not occur following hepatitis A infection and persisting liver damage is very rare.

7.3 Epidemiology

7.3.1 Global burden of disease

HAV is common in areas with poor sanitary conditions and limited access to clean water.1 In highly endemic areas, such as parts of Africa and Asia, the disease is virtually confined to early childhood and is not an important cause of morbidity.1, 2 Almost all adults in these areas are immune, and hepatitis A epidemics are uncommon. In intermediate endemicity areas, such as Central and South America, Eastern Europe and parts of Asia, children may not be infected in early childhood and reach adulthood without immunity. A high proportion of adolescents and adults are susceptible and large outbreaks are common. In low endemicity areas, such as the US and Western Europe, infection is less common but can occur in high-risk groups. Large outbreaks are usually rare, due to high levels of sanitation that stops person-to-person transmission.

Viral spread occurs readily in households, in early childhood services and in residential facilities that care for the chronically ill, disabled or those with a weakened immune system. In early childhood services, typically the adult guardian develops symptomatic disease while the primary source, the infected young child, is asymptomatic. The risk of spread in early childhood centres is proportional to the number of children aged under 2 years wearing nappies. Infection in these early childhood services is an important source of outbreaks for whole communities.

Other groups at the highest risk of contracting the disease include people in close contact with an infected person, and travellers to areas with high or intermediate rates of hepatitis A infection. Others also at greater risk of contracting HAV are people who have oral–anal sexual contact, illicit drug users, those with chronic liver disease, food handlers, and laboratory workers who handle the virus.

Universal and targeted programmes for childhood immunisation have been introduced in several countries, including Israel, the US and Australia. Acute HAV infection has almost been eradicated in areas with HAV immunisation programmes.

7.3.2 New Zealand epidemiology

The rate of HAV in New Zealand has declined from 145.7 per 100,000 in 1971 to 1.0 per 100,000 in 2015.3 This fall in rate is attributable to the use of HAV vaccination in travellers and a reduction in HAV prevalence overseas.

In 2015, 47 cases were notified compared with 74 in 2014.3 Hospitalisation status was recorded for 46 cases, of which, 24 (52.2 percent) were hospitalised.

The highest rates occurred in the 20–29 years and 40–49 years age groups (both 1.8 per 100,000), followed by the 15–19 years age group (1.6 per 100,000).3 Of the 44 cases with ethnicity information recorded, Pacific peoples had the highest notification rate (2.5 per 100,000), followed by the Asian (1.7 per 100,000) and Māori (0.9 per 100,000) ethnic groups.

Travel information was recorded for all cases: 24 cases (51.1 percent) had travelled overseas during the incubation period of the disease.3 The countries most frequently visited included Samoa (5 cases) and Fiji (4 cases).

Hepatitis A outbreaks continue to occur (see Figure 7.1). There were two outbreaks in 2015, involving nine cases.3 One outbreak, involving seven cases of hepatitis A reported from five DHBs, was food related.4 The cases were epidemiologically linked to the consumption of imported frozen berries.

Figure 7.1 illustrates the overall national downward trend since a peak of notifications in 1997.

Figure 7.1: Hepatitis A notifications, by year, 1997–2015
Figure 7.1: Hepatitis A notifications, by year, 1997–2015

Source: ESR

7.4 Vaccines

7.4.1 Available vaccines

Two inactivated HAV vaccines are currently registered (approved for use) and available (marketed) in New Zealand, as well as a combined HAV and HBV vaccine and two HAV and typhoid combined vaccines.

Funded vaccine

HAV vaccine is not on the Schedule, but is recommended and funded for certain high-risk groups, as shown in Table 7.1.

Other vaccines
Inactivated HAV vaccine
Combined HAV and HBV vaccine
Combined HAV and typhoid vaccines

The two HAV-typhoid combination vaccines contain inactivated HAV and purified Salmonella typhi Vi polysaccharide.

7.4.2 Efficacy and effectiveness

After one dose of monovalent HAV vaccine in healthy people, protective levels of antibody have been demonstrated by two weeks, and 94–100 percent of people vaccinated will seroconvert by four weeks.5

A second dose 6 to 18 months after the first is thought to be important for long-term protection, particularly in the absence of exposure to HAV.6, 7 In subjects with an impaired immune system, adequate anti-HAV antibody titres may not be obtained after a single dose.

HAV vaccines have not yet been approved for children aged under 12 months. The limited data on immunogenicity in infants indicates high levels of seroconversion, but those with passively acquired maternal anti-HAV have lower serum antibody titres.

HAV vaccines are highly effective in preventing clinical disease, with recorded efficacy measures of around 94–100 percent from six weeks post-vaccination. Where children, adolescents and young adults have been vaccinated in targeted and/or national programmes, there has been a rapid decline in disease incidence. This decline is through both direct and indirect (herd immunity) effects.6

Duration of immunity

Antibodies to two doses of HAV vaccine have been shown to persist in vaccinated adults for at least 17 years after vaccination, and up to 15 years in vaccinated children and adolescents.8 Mathematical models estimate that following completion of a two-dose series, protective levels of antibody will persist for 25 years or longer in adults and 14–20 years in children.8 Given that HAV has a long incubation period, it is possible that immune memory with no detectable circulating antibody may be sufficient for protection, as is the case with HBV and HepB.

7.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.9 Store at +2°C to +8°C. Do not freeze.

7.4.4 Dosage and administration

See Table 7.2 for dosage and scheduling information.

The monovalent HAV and HAV combination vaccines should be administered by intramuscular injection into the deltoid region of the upper arm in adults and older children, or the anterolateral aspect of the thigh in younger children (see section 2.2.3).

Co-administration with other vaccines

The monovalent HAV and HAV combination vaccines may be administered concurrently with other vaccines.8, 10 The vaccines should be given in separate syringes and at different injection sites.

Interchangeability of hepatitis A vaccines

The monovalent HAV vaccines may be used interchangeably to complete a two-dose course.10

7.5 Recommended immunisation schedule

7.5.1 Recommendations

Hepatitis A vaccines are not on the Schedule, but are recommended and funded for the high-risk groups in the shaded section of Table 7.1 below. They may also be employer-funded or funded during an outbreak (see section 7.8).

Table 7.1: Hepatitis A vaccine recommendations

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for the number of funded doses and any changes to the funding decisions.

Recommended and funded
Transplant patientsa
Children with chronic liver diseasea
Close contactsb of hepatitis A cases
Recommended but not funded

Adults with chronic liver disease:

  • chronic hepatitis B or C infection
  • other chronic liver disease.
Men who have sex with men
Travellers – including occupationalc and recreational travel.

Occupational groupsc exposed to faeces, including:

  • employees of early childhood services, particularly where there are children too young to be toilet trained
  • health care workers exposed to faeces
  • sewage workers
  • those who work with non-human primates (eg, zoos, research laboratories).
Food handlersc during community outbreaks.
Military personnelc who are likely to be deployed to high-risk areas.
  1. See also sections 4.2 and 4.3.
  2. Only one dose is funded for close contacts as protection is only required for the duration of the outbreak. For long-term protection, contacts may seek a second (unfunded) dose, after an interval of at least 6 months. Refer to the Communicable Disease Control Manual 201211 for a definition of contacts.
  3. May be employer-funded. See also section 4.6.
Individuals with chronic liver disease

HAV vaccine is recommended and funded for children with chronic liver disease and for children and adults undergoing transplants (see sections 4.2 and 4.3). People with chronic liver disease are not at increased risk for hepatitis A, but acute hepatitis A can have serious or fatal consequences.6

Chronic hepatitis B or C infection

Studies have shown that in these individuals, super-infection with HAV leads to increased morbidity and mortality.6

Other chronic liver disease

Non-immune individuals who have not been vaccinated should receive HAV vaccine before liver decompensation. It should be given as early as possible before liver transplantation; vaccination may be performed after transplantation, although the response is unlikely to be as good as early in liver disease.12, 13

Travellers

The first dose of HAV vaccine should be given as soon as travel is considered.8 The high and intermediate endemicity areas listed in section 7.3.1 may be used as a guide for recommending hepatitis A vaccination for travel, but there are limits to the data that informs these listings, and variation within countries. Even in low prevalence countries there is a risk of foodborne hepatitis A. In addition, decreasing prevalence in formerly endemic countries leads to large numbers of susceptible people and the risk of large outbreaks, as has recently been reported. The vaccine may be considered for all travellers aged 1 year and older.1

Immunoglobulin is not normally available or recommended in New Zealand for pre-travel use.

Certain occupational groups

Immunisation with HAV vaccine is recommended (but not funded) for people in occupational groups exposed to faeces, as listed in Table 7.1 above.

Others at higher risk

Pre-immunisation screening for anti-HAV antibodies is not routinely recommended. There is no danger in vaccinating an already immune person, but some groups with higher probability of prior infection may wish to avoid the expense of vaccination. These include:

Routine immunisation for children

HAV vaccine is not routinely recommended and is not on the Schedule for children in New Zealand. It should, however, be considered during community outbreaks (see section 7.8).

7.5.2 Immunisation schedule

Immunisation schedules for HAV-containing vaccines are provided in Table 7.2. See the manufacturers’ data sheets for more information. For the monovalent HAV vaccines, the first dose is for primary immunisation and the second dose is a booster.

Table 7.2: Hepatitis A-containing vaccines: by age, dose and schedule

Note: Havrix and Havrix Junior are funded for eligible individualsa (see Table 7.1).

Age Vaccine Dose Volume (mL) Number of doses Schedule
Hepatitis A vaccines
1–15 years Havrix Junior 720 EU 0.5 2 0 and 6–12 monthsb
2 years–adult Avaxim 160 antigen units 0.5 2 0 and 6–36 months
≥16 years Havrix 1440 1,440 EU 1 2 0 and 6–12 monthsb
Hepatitis A–Hepatitis B combined vaccine
1–15 years Twinrixc 720 EU of HAV and 20 µg of HBsAg 1.0 2 0 and 6–12 months
  Twinrix Juniord 360 EU of HAV and 10 µg of HBsAg 0.5 3 0, 1 and 6 months
≥16 years Twinrix 720 EU of HAV and 20 µg of HBsAg 1.0 3 0, 1 and 6 months; or 0, 7, 21 days plus a booster at 1 year
Hepatitis A–Typhoid combined vaccines
≥15 years Hepatyrix 1,440 EU of HAV and 25 µg of Vi 1.0 1 At least 14 days before departure; then boost with HAV vaccine at
6–12 monthse
≥16 years Vivaxim 160 antigen units of HAV and 25 µg of Vi 1.0 1 At least 14 days before departure; then boost with HAV vaccine at
6–36 monthse

Key: EU = enzyme-linked immunosorbent assay (ELISA) units of hepatitis A virus protein; HAV = hepatitis A virus; HBsAg = recombinant hepatitis B surface antigen; Vi = Salmonella typhi polysaccharide

Notes

  1. Note that two doses of hepatitis vaccine are funded for transplant patients and children with chronic liver disease; one dose is funded for close contacts of hepatitis A cases.
  2. Even after a longer interval between the 1st and 2nd doses, there is no need to restart the series. A substantial anamnestic response occurs after a 2nd dose given up to 8 years after the initial dose.14
  3. For children not previously exposed to the hepatitis A or B viruses. Source: GlaxoSmithKline NZ Ltd. 2016. Twinrix and Twinrix Junior New Zealand Data Sheet. URL: http://www.medsafe.govt.nz/profs/datasheet/t/Twinrixinj.pdf (accessed 4 December 2016).
  4. Use when the child is at immediate risk of exposure to hepatitis B (eg, travellers) and did not receive a primary course of HepB as an infant. Source: GlaxoSmithKline NZ Ltd. 2016. Twinrix and Twinrix Junior New Zealand Data Sheet. URL: http://www.medsafe.govt.nz/profs/datasheet/t/Twinrixinj.pdf (accessed 4 December 2016).
  5. If the individual remains at risk from typhoid fever, a single dose of the typhoid vaccine is recommended every 3 years.

7.5.3 Pregnancy and breastfeeding

The safety of HAV vaccine during pregnancy and while breastfeeding has not been determined. However, because HAV vaccine is produced from inactivated HAV, there is not expected to be any risk to the developing fetus and infant. As a precaution, HAV vaccines should be used during pregnancy only when clearly needed, such as when travelling to a country where HAV is endemic.

7.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

7.6.1 Contraindications

Administration of HAV vaccine should be delayed in individuals suffering from acute febrile illness. HAV vaccine should not be administered to people with a history of an anaphylactic reaction to a prior dose of HAV vaccine or to a vaccine component.

7.6.2 Precautions

In individuals with an impaired immune system, adequate anti-HAV antibody titres may not be obtained after a single dose.

Pregnancy is a precaution – see section 7.5.3.

7.7 Expected responses and AEFIs

7.7.1 Expected responses

Soreness, redness and swelling at the injection site, fever, malaise, headache, nausea and loss of appetite have been reported for the monovalent HAV vaccines, but these responses are usually mild and brief.15 Similar responses are seen with HAV–HBV combination vaccines, and HAV–typhoid combination vaccines.

7.7.2 AEFIs

Review of data from multiple sources has not identified any serious adverse events among children and adults that could be attributed to the HAV vaccine.15

7.8 Public health measures

7.8.1 Outbreak control

Vaccination

Age-appropriate vaccine is recommended for all close contacts aged older than 1 year. If time allows, consider pre-vaccine serology if there is a history or likelihood of previous HAV vaccination or infection (for example, previous residence in an endemic country). Post-exposure prophylaxis with vaccine should be offered to contacts as soon as possible, and within two weeks of last exposure to an infectious case. The efficacy of vaccine when administered more than two weeks after exposure has not been established.

Immunoglobulin

Where vaccine is contraindicated (or not immediately available), human normal immunoglobulin may be offered to a close contact who may have a reduced response to vaccine or has risk factors for severe disease. The dose is 0.03 mL/kg given by intramuscular injection. Post-exposure prophylaxis should be offered to contacts as soon as possible, and within two weeks of last exposure to an infectious case.

Close contacts aged under 1 year will require human normal immunoglobulin.

Human normal immunoglobulin is available from the New Zealand Blood Service. For further information, refer to the medicine data sheets or the New Zealand Blood Service website (www.nzblood.co.nz).

Early childhood services and other institutional outbreaks

If an outbreak occurs in an early childhood service, vaccination (and/or immunoglobulin if appropriate) may be indicated for all previously unimmunised staff and children at the service and unimmunised new staff and children for up to six weeks after the last case has been identified, including cases in the household of attendees. The number of infected cases should determine the extent of intervention.

Vaccination and/or immunoglobulin may also be indicated for adults and children at a school, hospital or custodial-care institution where an outbreak of hepatitis A is occurring. For sporadic cases in hospitals, schools or work settings, post-exposure prophylaxis is not routinely indicated, but careful hygiene practices should be maintained.

Community-wide outbreaks of hepatitis A infection

HAV vaccine is effective in controlling community-wide epidemics and common-source outbreaks of HAV infection.16 Before the vaccine is used for outbreak control, consideration should be given to the current epidemiology in the community, the population at risk should be defined, and the feasibility and cost of delivering a programme should be assessed.

For more details on control measures, refer to the ‘Hepatitis A’ chapter of the Communicable Disease Control Manual 2012.11

7.9 Variations from the vaccine data sheets

None.

References

  1. Nelson NP, Murphy TV. 2016. Hepatitis A. In: Brunette GW (ed). CDC Health Information for International Travel. URL: http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-a (accessed 4 December 2016).
  2. World Health Organization. 2016. Hepatitis A Factsheet. URL: http://www.who.int/mediacentre/factsheets/fs328/en/ (accessed 4 December 2016).
  3. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  4. Institute of Environmental Science and Research Ltd. 2016. Annual Summary of Outbreaks in New Zealand, 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualOutbreak/2015/2015OutbreakRpt.pdf (accessed 23 December 2016).
  5. Centers for Disease Control and Prevention. 2006. Prevention of Hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports 55(RR07):
    1–23. URL: www.cdc.gov/mmwr/PDF/rr/rr5507.pdf (accessed 6 February 2014).
  6. Murphy TV, Feinstone SM, Bell BP. 2013. Hepatitis A vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  7. Van Damme P, Banatvala J, Fay O, et al. 2003. Hepatitis A booster vaccinations: is there a need? The Lancet 362(9389): 1065–71.
  8. American Academy of Pediatrics. 2015. Hepatitis A. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  9. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  10. Department of Health and Ageing. 2016. Hepatitis A. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-4 (accessed 4 December 2016).
  11. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).
  12. Arslan M, Wiesner RH, Poterucha J, et al. 2001. Safety and efficacy of hepatitis A vaccination in liver transplantation recipients. Transplantation 72(2): 272–6.
  13. Arguedas MR, Johnson A, Eloubeidi MA, et al. 2001. Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients. Hepatology 34(1): 28–31.
  14. Iwarson S, Lindh M, Widerstrom L. 2004. Excellent booster response 4 to 8 years after a single primary dose of an inactivated hepatitis A vaccine. Journal of Travel Medicine 11(2): 120–1.
  15. Irving GJ, Holden J, Yang R, et al. Hepatitis A immunisation in persons not previously exposed to hepatitis A. Cochrane Database of Systematic Reviews 2012, Issue 7, Art. No. CD009051. DOI: 10.1002/14651858.CD009051.pub2 (accessed 14 January 2013).
  16. Averhoff F, Shapiro CN, Bell BP, et al. 2001. Control of hepatitis A through routine vaccination of children. Journal of the American Medical Association 19(286): 2968–73.

8 Hepatitis B

In this chapter:

Key information

8.1 Virology

8.2 Clinical features

8.3 Epidemiology

8.4 Vaccines

8.5 Recommended immunisation schedule

8.6 Contraindications and precautions

8.7 Expected responses and AEFIs

8.8 Public health measures

8.9 Variations from the vaccine data sheet

References

Key information

Mode of transmission Contact with infected blood or body fluids during childbirth (vertical transmission); sexual intercourse, intravenous drug use, or contact with broken skin (horizontal transmission).
Incubation period 45–180 days, commonly 60–90 days.
Period of communicability Potentially infectious 2–3 weeks before the onset of symptoms, during the clinical disease and usually for
2–3 months after acute hepatitis B illness; as long as HBsAg continues to be present in blood.
Burden of disease

New Zealand is a country with a low overall prevalence of hepatitis B carriage, but it contains certain populations with high prevalence.

All pregnant women and high-risk groups should be screened for chronic infection.

HBV acquisition in infancy is very likely to lead to chronic infection.

Chronic HBV infection can progress to cirrhosis and liver cancer.

Funded vaccines

HepB (HBvaxPRO).

DTaP-IPV-HepB/Hib (Infanrix-hexa).

Dose, presentation, route

HepB:

  • 5 µg presentation – 0.5 mL per dose
  • 10 and 40 µg presentations – 1.0 mL per dose
  • single dose vial.

DTaP-IPV-HepB/Hib:

  • 0.5 mL per dose
  • pre-filled syringe and glass vial – the vaccine must be reconstituted prior to injection.

Intramuscular injection.

Funded vaccine indications and schedule

At ages 6 weeks, 3 months and 5 months: DTaP‑IPV‑HepB/Hib.

Babies born to HBsAg-positive mothers should receive HepB vaccine plus HBIG at birth, then the usual childhood schedule. Serological testing (anti-HBs and HBsAg) at age 9 months.

Individuals with eligible conditions: HepB (see section 8.5).

Vaccine efficacy/ effectiveness In general, efficacy is 85–95 percent, though likely to be lower in older individuals and those with immunocompromise. Protection is expected to be lifelong. Boosters are not recommended.

8.1 Virology

The hepatitis B virus (HBV) is a partially double-stranded DNA virus belonging to the Hepadnaviridae family. Three major subunits make up the structural components:

The genome has four genes (S, C, X and P). Both the core nucleocapsid protein (HBcAg) and the ‘early’ protein (which makes HBeAg) are translated from the C gene. HBcAg is essential for viral packaging and is an integral part of the nucleocapsid. HBeAg is a soluble protein that is not part of the virus particle. Detection of HBeAg in the serum is correlated with viral replication, and is most commonly found in those with acute hepatitis B and those with chronic HBV infection with high viral load.1

8.2 Clinical features

There is a broad spectrum of clinical disease with HBV infection, from subclinical through to fulminant hepatitis. Persistent infection can lead to chronic liver disease, potentially causing cirrhosis or hepatocellular carcinoma.

8.2.1 Serological markers of infection

The HBV antigens and their associated antibodies are serological markers of HBV infection or vaccination (Table 8.1). At least one serological marker is present during the different phases of infection (Table 8.2).

Table 8.1: HBV antigens and their respective antibodies
Antigen Antibody
HBsAg
(hepatitis B surface antigen)
Anti-HBs (antibody to HBsAg),
(IgM, IgG, and total)
HBcAg
(hepatitis B core antigen)
Anti-HBc (antibody to HBcAg),
(IgM, IgG and total)
HBeAg
(hepatitis B e antigen)
Anti-HBe (antibody to HBeAg),
(IgM, IgG and total)
Table 8.2: Interpretation of serology for HBV infection
Serological marker Interpretation
HBsAg Total
anti-HBc
IgM
anti-HBc
Anti-HBs
Never infected
+ + + Acute infection
+ + + or – Acute resolving infection
+ + Recovered from past infection and is immune
+ + Chronic infectiona
+ Immune if ≥10 IU/L.b Vaccinated or natural infection.

Key: Anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen (HBsAg); IgM = immunoglobulin M; + = positive test result; – = negative test result.

  1. HBeAg positive (HBeAg+) correlates with high viral load and increased risk of transmission; HBeAg negative (HBeAg–) correlates with lower viral load and reduced risk of developing cirrhosis or cancer.
  2. Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.

Adapted from: Van Damme P, Ward J, Shouval D, et al. 2013. Hepatitis B vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders. Table 15.1.

See the ‘Hepatitis B’ chapter of the Communicable Disease Control Manual 20122 for recommendations for HBV case and contact management.

8.2.2 Acute hepatitis

The virus preferentially infects liver cells, multiplying there and releasing large amounts of HBsAg, which is present in the blood of people with active infection. The incubation period varies between 45 and 180 days, and is commonly 60 to 90 days.

HBV is not directly cytopathic; it is the host’s immune response that leads to death of the infected liver cell. Most infected people mount an effective immune response that leads to eradication of infection over a period of several months. Adults with acute infection may be asymptomatic (approximately 20 percent) or have symptomatic hepatitis (approximately 80 percent, but these proportions vary3).

The common symptoms of acute hepatitis B illness are fever, jaundice, malaise, anorexia, nausea, vomiting, myalgia and abdominal pain. Jaundice usually develops within two weeks of onset of the illness, and dark urine and/or clay coloured stools might appear up to five days before clinical jaundice. Clinical signs and symptoms of acute hepatitis B usually resolve one to three months later.1

There is a small risk of liver failure (less than 1 percent) with acute infection; almost half will die or require emergency liver transplantation.

8.2.3 Chronic HBV infection

The main burden of HBV disease occurs in people with chronic HBV infection. Chronically infected people are identified by presence and persistence of HBsAg in their serum for at least six months. The age of acquisition of HBV is strongly associated with the risk of developing chronic HBV infection. Approximately 90 percent of those infected perinatally or in infancy develop chronic HBV infection, compared with 30 percent of children infected between ages 1 and 4 years and less than 5 percent of people infected as adults.

Infants seldom mount an immune response to HBV infection, and infection in infancy is often asymptomatic. Asymptomatic chronic infection stimulates persistent immune responses that may eventually lead to cirrhosis (decades later); cirrhosis and chronic infection increase the risk of development of hepatocellular carcinoma.

Chronically infected people who are HBsAg positive can also have HBeAg detectable in the serum, and this combination is considered most infectious. Although recent evidence suggests HBeAg negative patients are less infectious, it is dependent on HBV DNA levels. Whatever the case, both groups can be an ongoing source of infection to susceptible individuals. In the early years of chronic infection, high rates of viral replication are common, and both HBeAg and high levels of HBV DNA are present in the blood. In later years, HBeAg may be absent from the blood, and HBV DNA levels are usually lower, both of which correspond with lower rates of viral replication.

8.2.4 Routes of transmission

HBV is usually transmitted through contact with infected blood or body fluids during childbirth, contact with broken skin, or during sexual intercourse or intravenous drug use. Although HBV can be found in all body fluids, blood has the highest concentration and saliva the lowest. HBV in dried blood remains infective for at least one week.4

Perinatal (vertical) transmission

The primary source of HBV infection is perinatal exposure from mothers with chronic HBV infection. Transmission usually occurs at the time of birth. The in utero transmission of HBV is relatively rare,5 accounting for less than 2 percent of infections transmitted from mother to infant.

If no prophylaxis is given to the infant, the baby of an HBeAg positive mother has a 70–90 percent risk of infection, while the baby of an HBeAg negative, HBsAg positive carrier mother has a 5–20 percent risk of infection. Over 90 percent of infants who acquire infection perinatally go on to become chronic carriers.

Person-to-person (horizontal) transmission

Non-sexual person-to-person transmission probably occurs from inadvertent percutaneous or mucosal contact with blood or infectious body fluids amongst people in close daily contact (household members).

The main sources of transmission are:

8.3 Epidemiology

8.3.1 Global burden of disease

Approximately two billion people have been exposed to HBV, and an estimated 240 million people have chronic infection and remain at risk of developing cirrhosis and hepatocellular carcinoma.6, 7 More than 90 percent of individuals with chronic HBV reside in the Asia–Pacific region, where most countries have high prevalence rates of HBV infection (the population rate of HBsAg positivity is between 5 and 20 percent). More than 99 percent of HBV-infected people in this region acquired infection through vertical transmission from their mother (usually at the time of delivery) or in early childhood. Acquisition of HBV during adulthood (usually via sexual transmission or injecting drug use) is associated with a high rate of symptomatic hepatitis but a low rate of chronic infection.

The introduction of universal childhood HBV immunisation has changed the epidemiology of chronic infection in many countries, but it will be several decades (one to two human generations) before the full benefits are realised. The world can be divided into regions with high (8 percent and over), high-intermediate (5–7 percent), low-intermediate (2–4 percent) and low (less than 2 percent) prevalence of chronic infection, defined as the presence of HBsAg in serum.8, 9

In regions with a high prevalence of chronic infection, the lifetime risk of exposure to HBV is almost 80 percent, with most infections occurring in the first decade of life. The Pacific Islands and most of Asia (except Japan and India) are high-prevalence regions. Other high-prevalence regions include Sub-Saharan Africa and Latin America.8 In contrast, in countries with a low HBsAg prevalence, the lifetime risk of HBV exposure is less than 20 percent, with most infections acquired in adulthood.

New Zealand has a low overall prevalence of hepatitis B carriage but contains certain populations with high prevalence (see section 8.3.2 below).

8.3.2 New Zealand epidemiology

Before the introduction of HBV immunisation in New Zealand, HBV transmission was common among preschool and school-aged children. The exact mode of transmission is uncertain but is thought to be related to close contact. In the eastern Bay of Plenty region almost half of the population were infected by age 15 years.10, 11 Even after the introduction of universal HepB in 1988 (see Appendix 1), there were regions in New Zealand where children were still at risk of HBV infection due to poor immunisation coverage rates.12, 13, 14

Acute HBV infection

Only acute hepatitis B is a notifiable disease in New Zealand. Therefore notification rates do not describe the burden of chronic HBV infections.

The HBV notification rate in 2015 was 0.7 per 100,000 population (34 cases), similar to the 2014 rate (0.8 per 100,000, 35 cases).15 The highest notification rate was in the 40–49 and 50–59 years age groups (both 1.3 per 100,000). The notification rate was higher for males (1.1 per 100,000 population) than for females (0.4 per 100,000).

Ethnicity was recorded for 32 cases (94.1 percent).15 The Māori (0.9 per 100,000) and European/Other (0.6 per 100,000) ethnic groups had the highest hepatitis B notification rates.

The most common risk factors reported in 2015 were overseas travel and sexual contact with a confirmed case or person with chronic HBV infection.

Hepatitis B notifications have declined from 609 cases in 1984 to 34 cases in 2015 (see Figure 8.1). While difficult to quantify accurately, the introduction of universal infant immunisation in 1988 has contributed to the dramatic decline in the number of newly notified cases of HBV infection.

Figure 8.1: Notifications of hepatitis B, 1971–2015
Figure 8.1: Notifications of hepatitis B, 1971–2015

Source: Ministry of Health and ESR

Chronic HBV infection

Approximately 100,000 people in New Zealand are chronically infected with HBV. The National Hepatitis B Screening Programme was a three-year programme that started in 1999 and targeted at-risk populations in the North Island (Māori, Pacific peoples and Asian New Zealanders aged over 15 years). The programme also enrolled people from other ethnic groups and included follow-up of individuals aged under 15 years with chronic HBV.

Approximately one-third of the at-risk populations were screened. Of these, the highest rates were among Chinese (9.1 percent), Pacific peoples (8.5 percent) and Māori (5.8 percent). Although Europeans were not specifically targeted in this screening programme, they have an estimated prevalence rate of 1 percent (higher than in Australia, North America and Europe), reflecting increased risk of childhood horizontal transmission.16

A New Zealand-based modelling study estimated that until the year 2100, people with chronic HBV infection will continue to provide a source of infection to susceptible people.17 Increased immigration from high-prevalence countries in the Asia–Pacific region is also likely to influence HBV prevalence in New Zealand.

Because people who acquire chronic HBV infection in childhood usually do not develop hepatocellular carcinoma until aged 40 years or older, the introduction of a universal HBV vaccination in 1988 is unlikely to have a significant effect on the incidence of hepatocellular carcinoma until approximately 2030.

A retrospective laboratory data study of antenatal HBsAg tests from the Midlands region (Bay of Plenty, Eastern Bay of Plenty, Waikato and Rotorua) between 1997 and 2009 found a declining prevalence of HBV infection. This decrease was seen across all age groups, but was most marked in the antenatal tests of women aged under 20 years, due to receipt of funded HepB in childhood.18

A recent long-term follow-up study in New Zealand has shown horizontally acquired HBV infection during childhood in Māori and Pacific peoples correlates with increased rates of hepatocellular carcinoma and liver-related mortality.19 This study emphasises the importance of early protection of the infant with vaccination.

Strategy for prevention

In 1988 New Zealand was one of the first countries to introduce universal infant hepatitis B immunisation. At the end of 2016 approximately 93 percent of New Zealand children aged 2 years had completed a primary course of HepB, which confers lifelong immunity in approximately 95 percent of vaccinees.

8.4 Vaccines

8.4.1 Available vaccines

A number of HBV-specific monovalent and combination vaccines that contain recombinant HBsAg (HepB) are licensed (approved for use) and available (marketed) in New Zealand.

Funded vaccines
Other vaccines

8.4.2 Efficacy and effectiveness

See also section 14.4.2 for information about the DTaP-IPV-HepB/Hib vaccine.

Immunogenicity

Clinical trials in high-risk groups have shown a vaccine efficacy of
85–95 percent. Serum anti-HBs antibody ≥10 IU/L is the WHO measure of immunity and is considered a correlate of protection. In the primary care setting, individuals who have had a documented seroconversion after three injections are expected to have lifelong immunity with no need for further boosters, even if circulating antibody is subsequently not detectable.

Smoking, obesity, HIV infection and chronic disease (including renal failure) all reduce vaccine efficacy, but age is the primary factor affecting the response. At least 98 percent of infants, 95 percent of children and 90 percent of adolescents develop protective levels of antibody after three doses of vaccine. Some non-responders to the initial vaccination course will not produce adequate antibody levels. These people should be offered a full second course of three injections.

However, some people are persistent non-responders. Persistent non-responders often have an impaired immune system, such as organ transplant recipients and those with HIV infection or chronic disease, including advanced cirrhosis, renal failure or those undergoing haemodialysis (see section 8.5.7).

For babies of HBeAg-positive mothers, controlled trials have shown that vaccine at birth provides 75 percent protection from infection, while administration of HBIG in addition to vaccination provides 85–95 percent protection against transmission.1, 20 Protection is reduced to less than 80 percent when the mother’s HBV DNA level is greater than 108 IU/mL (or 108 copies/mL). In this situation, administration of tenofovir (an antiviral agent) to the mother during the last trimester is recommended and funded.

Duration of immunity

The development of anti-HBs antibodies after a primary vaccination course (three injections and seroconversion) indicates development of immune memory. The quantity of antibody in serum is thought to determine the length of time the antibody titre can be detected in the blood, although any reading ≥10 IU/L post-vaccination course is considered protective. Once a seroprotective level is reached after the three-dose primary vaccination course, booster doses of vaccine are unnecessary.21, 22 Children who are given booster doses up to 12 years after the primary series show strong anamnestic (secondary) responses, indicating the boost was unnecessary.

There is evidence from Taiwan,23 Alaska24 and Hawaii25 that boosters of HepB are unnecessary following completion of infant immunisation. This is despite the fact that a large proportion of vaccinees will lose detectable antibodies within seven years of vaccination. Long-term protection from clinical infection despite loss of neutralising antibody is thought to reflect a strong cellular memory immune response following HBV vaccination. Vaccinees who are subsequently infected with HBV do not develop clinical illness but may have anti-HBc present in plasma.

Effects on chronic HBV infection

In all populations where it has been measured, immunisation has led to a dramatic drop in HBV chronic infection.26 For example, chronic HBV infection dropped from 16 percent to zero in Alaska as a result of 96 percent immunisation coverage. In Taiwan, the incidence of hepatocellular carcinoma also decreased in children as a result of the immunisation programme.27, 28

8.4.3 Transport, storage and handling

Transport hepatitis B vaccines according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.29 Store at +2°C to +8°C. Do not freeze.

DTaP-IPV-HepB/Hib should be stored in the dark.

8.4.4 Dosage and administration

Each 0.5 mL dose of DTaP-IPV-HepB/Hib (Infanrix-hexa) vaccine contains 10 μg of HBsAg, and is administered by intramuscular injection (see section 2.2.3).

The dose of HepB vaccine (5 μg HBsAg per 0.5 mL, 10 μg per 1.0 mL or 40 μg per 1.0 mL) varies according to the age of the individual and/or their health status. HepB vaccine is administered by intramuscular injection.

Co-administration with other vaccines

Hepatitis B vaccines may be given at the same time as all other vaccines on the Schedule, including measles, mumps and rubella (MMR) vaccine.

If a course of vaccine is interrupted, it may be resumed without repeating prior doses (see Appendix 2).

8.5 Recommended immunisation schedule

Table 8.3: Hepatitis B vaccine recommendations, funded and unfunded

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to the funding decisions.

Recommended and funded
Household or sexual contacts of HBsAg-positive patients (ie, patients with acute or chronic HBV infection)
Babies of HBsAg-positive mothers (ie, mothers with acute or chronic HBV infection) – require a birth dose plus the primary series (HBIG is also given to these babies at birth)
Children and adolescents aged under 18 years who are considered not to have achieved a positive serology and require additional vaccination or require a primary course of vaccination
HIV-positive patientsa
Hepatitis C-positive patientsb
Following non-consensual sexual intercourse
Following immunosuppressiona,c
Solid organ transplant patientsa
Post-HSCT patientsa
Following needle-stick injury
Dialysis patientsa,d
Liver or kidney transplant patientsa,d
Recommended, not funded
Adults at occupational risk (see section 4.6)

Adults at risk of infection by sexual exposure:

  • people seeking evaluation or treatment for a sexually transmitted infection
  • people with a high number of sexual partners
  • people who have sex with commercial sex workers
  • men who have sex with men
Individuals with haemophilia and other regular recipients of blood products
Prison inmates
Current or recent injecting drug users
Migrants from HBV endemic countries (HBsAg prevalence ≥2%)e
Individuals with developmental disabilities
Travellers to HBV endemic regions (HBsAg prevalence ≥2%)e
  1. See also section 4.3.3.
  2. Hepatitis C patients should also receive hepatitis A vaccine, although this is not currently funded.
  3. The period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days.
  4. The 40 µg dose of HepB is recommended for adult dialysis patients or for adult liver or kidney transplant patients. See Table 8.5.
  5. See the Centers for Disease Control and Prevention website for countries with HBsAg prevalence ≥2% (wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-b). Consider combined Hep A and B vaccination for travellers to these regions.

8.5.1 Usual childhood schedule

A primary course of hepatitis B vaccination is given as three doses of DTaP-IPV-HepB/Hib at ages 6 weeks, 3 months and 5 months (Table 8.4). If a course of immunisation is interrupted for any reason, it may be resumed without repeating prior doses (see section 8.5.3 and Appendix 2).

Table 8.4: Usual childhood schedule for hepatitis B-containing vaccine (excluding catch-up)
Age Vaccine Comment
6 weeks DTaP-IPV-HepB/Hib Primary series
3 months DTaP-IPV-HepB/Hib Primary series
5 months DTaP-IPV-HepB/Hib Primary series
Preterm infants of HBsAg-negative women

Some low birthweight or preterm infants may have a reduced response to HepB at birth.30 However, by the chronological age of 1 month, all medically stable preterm infants, regardless of initial birthweight or gestational age, respond to HepB as well as term and larger infants.31 Because New Zealand’s Schedule starts at age 6 weeks, low birthweight and preterm infants are expected to respond to HepB. (See also section 4.2.1.)

Infants with liver or renal disease

HepB vaccine is funded for liver or kidney transplant patients and for dialysis patients. For infants requiring transplants, see section 4.2.3. For infants undergoing dialysis, see ‘Chronic kidney disease (CKD)’ in section 4.3.3.

8.5.2 Babies born to HBsAg-positive mothers

The routine schedule for these infants is a birth dose of 5 µg of HepB plus HBIG, then three doses of hepatitis B (as DTaP-IPV-HepB/Hib) at ages 6 weeks, 3 months and 5 months.

All pregnant women should receive antenatal screening for hepatitis B infection by testing for HBsAg. Babies of HBsAg-positive mothers are to be notified at birth using the form HE1446: Consent for hepatitis B vaccine and hepatitis B immunoglobulin and notification to the Medical Officer of Health, available from www.healthed.govt.nz or the local authorised health education resource provider or public health unit.

The vitamin K injection may also be given at the same time, in the same limb as the HBIG, but not at the same site.

Occasionally women have not been tested for their HBsAg status during the antenatal period. If a woman’s HBsAg status is unknown at the time of delivery, the baby should be given HepB at the time of delivery while waiting for the result of an urgent HBsAg test on the mother. If she is found to be HBsAg positive, the baby should be given HBIG as soon as possible, up to seven days post-delivery.31 Subsequent vaccine doses are given as per the Schedule.

It is essential to take blood to determine whether the baby has seroconverted (anti-HBs positive) or has become infected despite immunoprophylaxis (HBsAg positive), or is neither infected nor immune (ie, HBsAg negative and anti-HBs negative). Testing should not be performed before 9 months of age to avoid detection of anti-HBs from HBIG administered during infancy and to maximise the likelihood of detecting late HBV infections.31

Figure 8.2: Management of a baby of an HBsAg-positive woman
Screen all women in early pregnancy for hepatitis B carriage

Woman is HBsAg positive

No

See section 8.5.1: ‘Usual childhood schedule’

Yes

All HBsAg-positive pregnant women should also be tested for HBeAg and should have HBV DNA measured. The results should be discussed with a specialist or the woman should immediately be referred to a specialist for ongoing care.

Give the baby hepatitis B protection as follows.

At age Action to be taken
Birth Give HBIG 100–110 IU and HepB 5 µg
6 weeks DTaP-IPV-HepB/Hib
3 months DTaP-IPV-HepB/Hib
5 months DTaP-IPV-HepB/Hib
9 months

Take a blood test to check for hepatitis B infection (HBsAg) and for vaccine-induced immunity (anti-HBs).

  • If HBsAg is negative and anti-HBs level is ≥10 IU/L* at age 9 months, immunity is proven.
  • If HBsAg is positive, the baby has become infected despite prophylaxis: refer to an appropriate specialist.

If HBsAg is negative and anti-HBs level is <10 IU/L* at age 9 months, give a further 3 doses of HepB at least 4 weeks apart. Recheck serology 4 weeks after the last dose. If there is no seroconversion after the third further dose of HepB (ie, if anti-HBs is still <10 IU/L*), discuss with a specialist.

All other vaccines should be administered as per the Schedule.

*     Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.

Neonatal HBIG plus vaccine will fail to prevent vertical HBV transmission in more than 20 percent of infants born to HBsAg-positive mothers with serum HBV DNA levels greater than 108 IU/mL (or 108 copies/mL). These mothers are usually young, with normal alanine transaminase, and are HBeAg positive. If the mother’s HBV DNA level is greater than 108 IU/mL, administration of tenofovir (an antiviral agent) during the last trimester is recommended and funded.

The number of such high-risk pregnancies appears to be increasing in this country as a result of the immigration of young Asian women of childbearing age, of whom approximately 8 percent are HBsAg positive, with the majority of those also HBeAg positive. In contrast, the number of HBsAg-positive Māori and Pacific women of childbearing age has decreased markedly due to infant vaccination. In addition, most HBsAg‑positive Māori and Pacific women are HBeAg negative, with lower HBV DNA levels (below 108 IU/mL).

Babies born to mothers who received oral antiviral therapy for chronic HBV must still receive the recommended neonatal HBIG/vaccine schedule. All other vaccines are administered as per the Schedule.

See Appendix 6 and section 8.8.1 for more information about passive immunisation and HBIG.

Preterm and low birthweight infants of HBsAg-positive women

Preterm and low birthweight infants of HBsAg-positive women should be managed as above, regardless of birthweight or gestation.

8.5.3 Catch-ups for children and adolescents

HepB is recommended and funded for everyone aged under 18 years. If the HepB is not given during the first year of life, three doses of vaccine are recommended. An accelerated two-dose regimen for adolescents aged 11–15 years has been shown to be effective and to improve compliance in this age group. See Appendix 2 for catch-up schedules.

Children and adolescents with liver or kidney disease

HepB vaccine is funded for liver or kidney transplant patients (recommend six months post-transplant) and for dialysis patients.

See Figures 8.3 and 8.4 for serological testing and vaccination recommendations. If non-immune, children aged under 16 years should receive three doses of 10 µg HepB (at 0, 1 and 6 months), those aged 16 years and older should receive three doses of 40 µg HepB. If there is an inadequate immune response to the initial three-dose HepB series (see Figure 8.4), give a further three doses (10 µg or 40 µg, as appropriate).

See also ‘Chronic kidney disease (CKD)’ and ‘Solid organ transplants’ in section 4.3.3.

8.5.4 Eligible adults aged 18 years and older

Table 8.5: Hepatitis B vaccine schedules for eligible adults aged 18 years and older
Who Vaccine Dose Volume (mL) Number of doses Schedule
Dialysis patients, liver or kidney transplant patients HepB 40 µg 1.0 3 0, 1, and 6 months*
HIV patients HepB 10 µg 1.0 4 0, 1, 2, and 12 months
Other eligible adults (see Table 8.3) HepB 10 µg 1.0 3 0, 1, and 6 months*

*        Check the manufacturer’s data sheet for accelerated immunisation schedules.

Adult dialysis or adult liver or kidney transplant patients

These adults may have a reduced response to HepB,32 so the higher-dose (40 µg) formulation is recommended and funded. See section 8.5.7 for information about post-vaccination serology.

(See also ‘Solid organ transplants’ in section 4.3.3.)

Adult HIV patients

Adult HIV patients should receive four doses of HepB (10 µg) at 0, 1, 2 and 12 months.

(See also ‘HIV infection’ in section 4.3.3.)

Other eligible adults

Three doses of 10 µg HepB given at 0, 1 and 6 months are recommended. Shorter intervals between the second and third doses lead to lower antibody levels but equivalent seroconversion and therefore provide adequate protection. In healthy adults, a two-dose schedule separated by six months,33 a three-dose schedule given over three weeks,34 and various other accelerated schedules have led to seroconversion rates equivalent to those obtained when following the usual recommended schedule. In general, three doses separated by four-week intervals are recommended, but the doses may be delivered at weekly intervals if more rapid protection is needed.

8.5.5 Pregnancy and breastfeeding

HepB may be given during pregnancy and while breastfeeding. Acute HBV infection in pregnant women may result in severe acute hepatitis for the mother, with associated increased risk of fetal loss or neonatal infection. Vaccination should not be withheld from a susceptible pregnant woman at increased risk of acquiring hepatitis B (eg, the sexual partner of an injecting drug user, or known infected male).

8.5.6 (Re-)vaccination

Hepatitis B-containing vaccines are funded for (re-)vaccination of eligible children, as follows. See also sections 4.2 and 4.3.

DTaP-IPV-HepB/Hib (Infanrix-hexa)

An additional four doses (as appropriate) of DTaP-IPV-HepB/Hib are funded for (re-)vaccination of children aged under 10 years:

Up to five doses of DTaP-IPV-HepB/Hib are funded for children aged under 10 years receiving solid organ transplantation.

HepB (HBvaxPRO)

HepB is funded for children aged under 18 years who are considered not to have achieved a positive serology and require additional vaccination.

8.5.7 Serological testing

Screening for chronic infection

Screening for the antigen (HBsAg) is useful where there is increased likelihood of the individual already being infected.

The Hepatitis Foundation of New Zealand35 recommends that the following individuals are most at risk of HBV – people who:

Screening for HBsAg is also part of routine antenatal care (see section 8.5.2).

All HBsAg-positive individuals should be offered follow-up under the Hepatitis Foundation Hepatitis B Follow-up Programme to enable early diagnosis and treatment of the complications of severe liver disease and hepatocellular carcinoma. Vaccination is recommended (and funded) for household or sexual contacts of HBsAg-positive people (ie, contacts of people with acute or chronic HBV infection).

Serological testing for high-risk groups

Serological testing is only indicated in high-risk groups (see Table 8.6). These high-risk groups are at higher risk of exposure to HBV, at higher risk of having severe disease or are more susceptible to disease. A flow diagram (Figure 8.3) is included to assist in deciding whether pre- and/or post-vaccination serological testing is indicated. Figure 8.3 may be used for any individual aged 12 months or older, such as for the management of blood and body fluid exposures, or when an adult presents to primary care.

Table 8.6: Individuals at high-risk of hepatitis B infection, for whom serological testing is indicated
Household or sexual contacts of HBsAg-positive patients (ie, patients with acute or chronic HBV infection)
Current or recent injecting drug users
Individuals who change sexual partners frequently (eg, sex workers)
Immunocompromised individuals, including HIV-positive patients
Following non-consensual sexual intercourse
Individuals on immunosuppressive therapies for 28 days or more
Solid organ and post-HSCT patients
Following percutaneous injury (eg, needle-stick injury)
Adults at occupational risk (see section 4.6)
Individuals with haemophilia and other regular recipients of blood products
Inmates of custodial institutions
Individuals with developmental disabilities
People with chronic disease (eg, chronic renal failure requiring haemodialysis, or chronic liver disease)
Migrants from HBV endemic regions (HBsAg prevalence ≥2%)*

*     See the Centers for Disease Control and Prevention website for countries with HBsAg prevalence ≥2% (wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-b). Consider combined Hep A and B vaccination for travellers to these regions.

Figure 8.3: Flow diagram for serological testing for hepatitis B
Figure 8.3: Flow diagram for serological testing for hepatitis B
  1. HBIG may be recommended for non-immune individuals. See Table 8.7.
  2. Do not count any birth doses of HepB vaccine. See Table 8.3 for the list of funded conditions for HepB vaccine.
  3. See the manufacturer’s data sheet for accelerated HepB schedules.
  4. Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.
The non-responder protocol

Most vaccinees will develop a high anti-HBs titre, usually greater than 100 IU/L, which usually wanes over time.

Fully vaccinated individuals (ie, three documented doses of HepB) who have at any time had anti-HBs ≥10 IU/L do not need any booster doses, even if antibodies subsequently wane to undetectable levels, which occurs in most individuals by seven years after the last vaccination. If exposed, they will have a secondary anamnestic immune response that will prevent replication of the virus.1, 36 (Note: Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.)

If a high-risk individual does not achieve a titre of ≥10 IU/L, they should be considered a non-responder and follow the non-responder protocol (Figure 8.4).

*     Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.

Intradermal injections to correct this hyporesponsiveness that have been used in the past, but they are technically difficult and not recommended.

8.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

The only specific contraindication to HepB is anaphylaxis following a previous dose, or individuals with a history of allergic reactions to yeast or any of the vaccine’s components. This is uncommon. Immunisation of previously infected subjects is wasteful, but not harmful.

See section 14.6 for contraindications and precautions to DTaP‑IPV‑HepB/Hib vaccine.

8.7 Expected responses and AEFIs

See section 14.7 for expected responses and AEFIs with DTaP‑IPV‑HepB/Hib vaccine.

8.7.1 Expected responses

Minor side-effects – including local tenderness and redness, nausea, diarrhoea, general malaise and fever – are more common in adults than in children and, except for local reactions, occur at rates close to those seen with a placebo. Minor reactions reported after receiving the vaccine include a temperature >37.7°C in 1–6 percent, pain in 3–29 percent, and erythema, headache or swelling in 3 percent of vaccinees.

8.7.2 AEFIs

Allergic reactions have been reported but are rare. Anaphylaxis is extremely rare.

A number of studies have examined and failed to find disease events linked to hepatitis B immunisation.38 These studies have documented no increased risk of multiple sclerosis,39, 40 diabetes, chronic fatigue syndrome,41 encephalomyelitis or hair loss.42 Rarely, transient thrombocytopenia43 and myalgia and arthralgia44, 45 have been reported after HepB vaccination.

8.8 Public health measures

The elimination of HBV transmission is now a realistic public health goal,7, 46 especially with the proven effectiveness and safety record of HepB.47

It is important to ensure vaccination programmes are maintained for the at-risk populations, especially babies of mothers with chronic hepatitis B infection.

Babies born to HBsAg-positive mothers should be notified at birth. The prevention of perinatal transmission is covered in section 8.5.2.

8.8.1 Passive immunisation

HBIG is prepared from donated blood plasma and contains high levels of anti-HBs antibody (see Appendix 6). It is given after exposure to HBV and provides passive anti-HBs antibody protection against acute and chronic HBV disease. HBIG prophylaxis should be given in combination with the HepB to confer both passive and active immunity after exposure.

The efficacy of HBIG alone in preventing clinical hepatitis B infection is about 75 percent in adults, but the protection lasts only for a few months.1

Whenever immediate protection is required, immunisation with a vaccine should be combined with simultaneous administration of HBIG at a different site. It has been shown that passive immunisation with HBIG does not suppress the active immune response to vaccination. A single dose of HBIG (usually 400 IU for adults, 100–110 IU for the newborn; refer to the ‘Hepatitis B’ chapter of the Communicable Disease Control Manual 20122) is sufficient. If infection has already occurred at the time of the first immunisation, virus replication is unlikely to be inhibited completely, but severe illness and, more importantly, the development of chronic HBV infection may be prevented, particularly in the infants of HBsAg-positive mothers.

The management of contacts is summarised in Table 8.7.

Table 8.7: Management of contacts of hepatitis B cases
Contact Serological testing of contact (HBsAg, anti‑HBs, anti-HBc, IgM and IgG) Immunoglobulin
(if within 7 days of onset of case’s symptoms)
Immunisation
Any sexual contact, including protected sex Yes Yes, immediately after blood taken Yes, immediately after blood taken
Household, mucosal or percutaneous Yes Yes, if serology negative Yes, if serology negative
Other Yes No Yes, if serology negative

Source: Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 20 March 2017).

For more details on control measures, refer to the ‘Hepatitis B’ chapter of the Communicable Disease Control Manual 2012.2

8.9 Variations from the vaccine data sheet

See section 14.9 for variations from the DTaP-IPV-HepB/Hib (Infanrix‑hexa) data sheet.

References

  1. Van Damme P, Ward J, Shouval D, et al. 2013. Hepatitis B vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  2. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).
  3. McMahon BJ, Alward WLM, Hall DB, et al. 1985. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. Journal of Infectious Diseases 151(4): 599–603.
  4. Bond WW, Favero MS, Petersen NJ, et al. 1981. Survival of hepatitis B virus after drying and storage for one week. The Lancet 317(8219): 550–1.
  5. Alter HJ. 2012. To have B or not to have B: vaccine and the potential eradication of hepatitis B. Journal of Hepatology 57(4): 715–7.
  6. Papastergiou V, Lombardi R, MacDonald D, et al. 2015. Global epidemiology of hepatitis B (HBV) infection. Current Hepatology Reports 14(3): 171–8. DOI: 10.1007/s11901-015-0269-3 (accessed 5 December 2016).
  7. World Health Organization. 2016. WHO Global Health Sector Strategy on Viral Hepatitis 2016–2021. URL: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf?ua=1 (accessed 5 December 2016).
  8. Ott JJ, Stevens GA, Groeger J, et al. 2012. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 30(12): 2212–19.
  9. Centers for Disease Control and Prevention. 2016. Hepatitis B. In: CDC Health Information for International Travel (2016 Yellow Book). URL: https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-b (accessed 5 December 2016).
  10. Milne A. 1985. Prevalence of hepatitis B infections in a multiracial New Zealand community. New Zealand Medical Journal 98(782): 529–32.
  11. Moyes CD, Milne A. 1986. Hepatitis B markers in 14–15 year olds in the Bay of Plenty. New Zealand Medical Journal 99(809): 662–4.
  12. Stehr-Green, Briasco C, Baker M, et al. 1992. How well are we protecting our children? An immunisation coverage survey in Hawke’s Bay. New Zealand Medical Journal 105(938): 277–9.
  13. Ramadas D, Moyes CD, Ramadas G. 1992. Immunisation status of children in the Eastern Bay of Plenty. New Zealand Medical Journal 105(942): 378–9.
  14. Rainger W, Solomon N, Jones N, et al. 1998. Immunisation coverage and risk factors for immunisation failure in Auckland and Northland. New Zealand Public Health Report 5(7): 49–51.
  15. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  16. Robinson T, Bullen C, Humphries W, et al. 2005. The New Zealand Hepatitis B Screening Programme: screening coverage and prevalence of chronic hepatitis B infection. New Zealand Medical Journal 118(1211): U1345.
  17. Mann J, Roberts M. 2011. Modelling the epidemiology of hepatitis B in New Zealand. Journal of Theoretical Biology 269(1): 266–72.
  18. Addidle M. 2011. Impact of universal hepatitis B vaccination on antenatal hepatitis B prevalence in the Midlands region of the North Island, New Zealand. New Zealand Medical Journal 124(1332): 40–4.
  19. Lim TH, Gane E, Borman B, et al. 2015. Serological and clinical outcomes of horizontally transmitted chronic hepatitis B infection in New Zealand Māori: results from a 28-year follow-up study. Gut 64(6): 966–72. DOI: 10.1136/gutjnl-2013-306247 (accessed 24 December 2016).
  20. Lee C, Gong Y, Brok J, et al. 2006. Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis. British Medical Journal 332(7537): 328–36.
  21. Moyes CD, Milne A, Waldon J. 1990. Very low dose hepatitis B vaccination in the newborn: anamnestic response to vaccine at four years. Journal of Medical Virology 30(3): 216–18.
  22. West DJ, Calandra GB. 1996. Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination. Vaccine 14(11): 1019–27.
  23. Su WJ, Liu CC, Liu DP, et al. 2012. Effect of age on the incidence of acute hepatitis B after 25 years of a universal hepatitis B immunization program in Taiwan. Journal of Infectious Diseases 205(5): 757–62.
  24. McMahon BJ, Bulkow LR, Singleton RJ, et al. 2011. Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology 54(3): 801–7.
  25. Perz JF, Elm JL Jr, Fiore AE, et al. 2006. Near elimination of hepatitis B virus infections among Hawaii elementary school children after universal infant hepatitis B vaccination. Pediatrics 118(4): 1403–8.
  26. Chen D-S. 2009. Hepatitis B vaccination: the key towards elimination and eradication of hepatitis B. Journal of Hepatology 50(4): 805–16.
  27. Lee CL, Ko YC. 1997. Hepatitis B vaccination and hepatocellular carcinoma in Taiwan. Pediatrics 99(3): 351–3.
  28. Chang M-H. 2011. Hepatitis B virus and cancer prevention. In: Senn H-J, Otto F (eds). Clinical Cancer Prevention Berlin & Heidelberg: Springer.
  29. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  30. Committee on Infectious Diseases. 1994. Update on timing of hepatitis B vaccination for premature infants and for children with lapsed immunisation. Pediatrics 94(3): 403–4.
  31. American Academy of Pediatrics. 2015. Hepatitis B. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  32. Roukens AH, Visser LG. 2011. Hepatitis B vaccination strategy in vaccine low and non-responders: a matter of quantity of quality? Human Vaccines 7(6): 654–7. DOI: http://dx.doi.org/10.4161/hv.7.6.14986 (accessed 23 January 2017).
  33. Marsano LS, West DJ, Chan I, et al. 1998. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine 16(6): 624–9.
  34. Marchou B, Excler JL, Bourderioux C, et al. 1995. A three-week hepatitis B vaccination schedule provides rapid and persistent protective immunity: a multicenter, randomized trial comparing accelerated and classic vaccination schedules. Journal of Infectious Diseases 172(1): 256–60.
  35. Hepatitis Foundation of New Zealand. Who is at risk of hepatitis B? URL: http://www.hepatitisfoundation.org.nz/index.php/hepb/am-i-risk/ (accessed 23 January 2017).
  36. European Consensus Group on Hepatitis B Immunity. 2000. Are booster immunisations needed for lifelong hepatitis B immunity? The Lancet 355(9203): 561–5.
  37. Cardell K, Akerlind B, Sallberg M, et al. 2008. Excellent response to a double dose of the combined hepatitis A and B vaccine in previous non-responders to hepatitis B vaccine. Journal of Infectious Diseases 198(3): 299–304.
  38. Institute of Medicine: Committee to Review Adverse Effects of Vaccines. 2012. Adverse Effects of Vaccines: Evidence and causality. URL: http://www.nap.edu/catalog.php?record_id=13164 (accessed 29 October 2013).
  39. Expanded Programme on Immunization (EPI). 1997. Lack of evidence that hepatitis B vaccine causes multiple sclerosis. Weekly Epidemiological Record 72(21): 149–52.
  40. Sadovnick AD, Scheifele DW. 2000. School-based hepatitis B vaccination programme and adolescent multiple sclerosis. The Lancet 355(9203):
    549–50.
  41. Report of the working group on the possible relationship between hepatitis B vaccination and the chronic fatigue syndrome. 1993. Canadian Communicable Disease Report 19(4): 25–8.
  42. Wise R, Kiminyo K, Salive M. 1997. Hair loss after routine immunizations. Journal of the American Medical Association 278(14): 1176–8.
  43. Ronchi F, Cecchi P, Falcioni F, et al. 1998. Thrombocytopenic purpura as an adverse reaction to recombinant hepatitis B vaccine. Archives of Disease in Childhood 78(3): 273–4.
  44. McMahon BJ, Helminiak C, Wainwright RB, et al. 1992. Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons. American Journal of Medicine 92(3): 254–6.
  45. Fisher MA, Eklund SA, James SA, et al. 2001. Adverse events associated with hepatitis B vaccine in US children less than six years of age, 1993 and 1994. Annals of Epidemiology 11(1): 13–21.
  46. Ni YH, Chang MH, Wu JF, et al. 2012. Minimization of hepatitis B infection by a 25-year universal vaccination program. Journal of Hepatology 57(4): 730–5.
  47. Romanò L, Paladini S, Van Damme P, et al. 2011. The worldwide impact of vaccination on the control and protection of viral hepatitis B. Digestive and Liver Disease 43(Suppl 1): S2–7.

9 Human papillomavirus (HPV)

In this chapter:

Key information

9.1 Virology and the causal link to cancer

9.2 Clinical features

9.3 Epidemiology

9.4 Vaccines

9.5 Recommended immunisation schedule

9.6 Contraindications and precautions

9.7 Expected responses and AEFIs

9.8 Cancer prevention measures

9.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission Skin-to-skin contact, predominantly sexual, with a person with HPV infection.
Links to cancer HPV is linked to almost all cervical cancers and to about 69% of vulvar, 75% of vaginal, 63% of penile, 90% of anal and 70% of oropharyngeal cancers.
Incidence/ prevalence HPV infection is very common, with initial infection occurring soon after sexual debut and a lifetime risk of over 80%. Recurrent infection and co-infection with multiple types are possible.
Funded vaccine

HPV9 (Gardasil 9) is a recombinant subunit vaccine containing virus-like particles (VLPs).

HPV9 contains HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58.

Dose, presentation, route

0.5 mL per dose.

Pre-filled syringe.

Intramuscular injection.

Funded indications and recommended schedules

2 doses, at 0 and 6–12 months for children aged 14 years and under.

3 doses, at 0, 2 and 6 months, for individuals:

  • aged 15–26 years inclusive
  • aged 9–26 years inclusive:
    • with confirmed HIV infection OR
    • who are transplant (including stem cell) patients.

An additional dose for individuals aged 9–26 years post-chemotherapy.

NB: Individuals who were previously fully vaccinated with HPV4 are not eligible for HPV9.

Vaccine efficacy/ effectiveness

The incidence of HPV infection, precancerous lesions and genital warts is significantly reduced in immunised populations (in women and men).

There is evidence for herd immunity (reductions in HPV infection and genital warts in unimmunised populations).

Pregnancy HPV vaccines are not recommended for pregnant women; however, enquiring about the possibility of pregnancy is not necessary before vaccination.
Adverse events to vaccine Syncope (fainting) is a known injection reaction in adolescents.
Cancer prevention measures

HPV immunisation.

Regular cervical screening for women.

Safer sex approaches.

9.1 Virology and the causal link to cancer

Human papillomaviruses (HPVs) are small, non-enveloped DNA viruses from the Papillomavirus family. There are about 150 different HPV serotypes. They vary in their preference for infecting squamous epithelium at different sites, thereby causing the various types of HPV infection (eg, common, palmar, plantar or anogenital). More than 40 HPV types can infect the anogenital tract.1, 2

Data from the US cancer registry3 indicates that HPV is causally associated with almost all cervical cancers, about 69 percent of vulvar, 75 percent of vaginal, 63 percent of penile, 90 percent of anal and 70 percent of oropharyngeal cancers (see Table 9.1).

On the basis of their causal link to cancer, HPVs are divided into low-risk and high-risk types. There are approximately 12 high-risk types, which include 16, 18, 31, 33, 45, 52 and 58. Types 16 and 18 are most frequently associated with cervical cancer but are also causally associated with other cancers. In the US, HPV types 16 and 18 are estimated to cause 66 percent of invasive cervical cancers, 80 percent of anal, 49 percent of vulvar, 55 percent of vaginal, 48 percent of penile and 60 percent of oropharyngeal cancers annually3 (Table 9.1).

Low-risk types are predominantly associated with non-malignant lesions, such as genital warts (especially types 6 and 11), and can also cause recurrent respiratory papillomatosis.

Table 9.1: Average annual percentage of cancer cases attributable to HPV, by anatomic site and sex, United States, 2008–2010
Anatomic sitec Cancers attributable to any HPVa,b Cancers attributable to
HPV 16, 18a,b
Cancers attributable to HPV 31, 33, 45, 52, 58a,b
% % %
Cervix 90.6d 66.2 14.7
Vulva 68.8 48.6 14.2
Vagina 75.0 55.1 18.3
Penis 63.3 47.9 9.0
Anus      
  • women
92.5 79.5 10.8
  • men
88.7 79.1 3.8
Oropharyngeal      
  • women
63.3 50.8 9.5
  • men
72.4 63.4 4.4
  1. Data is from 2008–2010 diagnosis years from population-based cancer registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results Program.
  2. These estimates do not take into account future changes in incidence, population structure, or the percentage of cancers that are HPV positive.
  3. International Classification of Diseases (ICD) codes: Cervix C53; Vulva C51; Vagina C52; Penis C60; Anus C21; Oropharyngeal (includes cancers of the soft palate, walls of pharynx, tonsils and base of tongue) C01.9, C02.4, C02.8, C05.1, C05.2, C05.9, C09.0, C09.1, C09.8, C09.9, C10.0, C10.2, C10.8, C10.9, C14.0, C14.2, and C14.8.
  4. Although HPV is accepted to be a necessary factor in the causal pathway to invasive cervical cancer, HPV is not always detected in tumour specimens from women who receive a diagnosis of invasive cervical cancer due to a variety of reasons, including misclassification of tissue specimens as cervix, quality of tissue specimens, assay sensitivity, and a small proportion of HPV-negative, cervical cancers.

Adapted from: Saraiya M, Unger ER, Thompson TD, et al. 2015. US Assessment of HPV types in cancers: Implications for current and 9-valent HPV vaccines. Journal of the National Cancer Institute 107(6), Table 4. DOI: 10.1093/jnci/djv086 (accessed 14 September 2016).

9.2 Clinical features

9.2.1 Infection

Infection results from skin-to-skin contact, predominantly sexual, with a person with HPV infection. Transmission in the genital region may occur even when condoms are used and does not necessarily require penetrative intercourse. HPV may also be transmitted perinatally, from mother to newborn baby.

Clinically apparent warts are probably more infectious than subclinical infection. The virus penetrates micro-abrasions in the epithelium to reach the basal epithelial cells, where it causes the infected cells to produce proteins that delay cellular maturation. Continued replication of these infected cells in the intermediate epithelial layer, followed by virus replication in the superficial epithelial layer, results in the cellular overgrowth typical of warts.

For most people, HPV infection is transient and becomes undetectable by DNA testing within 6 to 12 months, but in some cases, HPV infection remains latent and may reactivate years later. As it is difficult to detect HPV in its latent stage, it is impossible to know whether in some cases the immune system can completely clear the virus or whether the virus remains latent at undetectable levels, capable of re-emerging later on.

Acquisition of HPV

Infection with oncogenic serotypes of HPV is common, with an estimated 70–80 percent of sexually active individuals becoming infected at some stage during their life. Initial infection occurs soon after sexual debut.

Most episodes of infection become undetectable by DNA testing within two years of acquisition; the average duration of infection is one year. Previous infection does not necessarily create long-term immune memory so does not prevent future re-infection with the same HPV type.

At any one time, approximately 10 percent of women have at least one HPV infection. The HPV serotypes that cause more prolonged infection tend to be those that more frequently result in the development of histological abnormalities.4, 5

The rate of acquisition of HPV is similar in men and women; however, there are differences between the sexes in the immune response to HPV. A smaller proportion of men are HPV-seropositive, and men have lower antibody titres than women.6 In contrast to women, for whom the risk for HPV acquisition increases with age through the early 20s and then decreases, studies have demonstrated HPV prevalence in men seems to peak at slightly older ages and remains constant or decreases slightly with increasing age, suggesting persistent HPV infection or a higher rate of re-infection.7, 8

Men who have sex with men, especially those that are HIV-positive, are at higher risk for HPV infection, anal cancer and high-grade anal intraepithelial neoplasia.9 In teenage men who have sex with men (aged 16–20 years), early and high per-partner HPV transmission occurred between men soon after their first sexual experiences.10

Individuals who are immunocompromised (due to medical conditions or treatment) are more likely to develop a persistent HPV infection and to subsequently progress to HPV-related disease.11, 12 Those with confirmed HIV infection are more at risk of HPV infection.13 HIV-infected individuals who are co-infected with HPV are less likely to become undetectable.14, 15 A direct relationship has been identified between low CD4+ cell count and an increased risk of cervical cancer in HIV-infected women.16

9.2.2 Cervical cancer

HPV rapidly becomes undetectable in the first 6–12 months of acquisition of infection, with 80–90 percent undetectable by two years. Following this, there is a very small fraction of persistent infection that progresses to cervical intraepithelial neoplasia (CIN); these are non-invasive precancerous lesions, which are categorised as either low or high grade CIN. Invasive cervical cancer occurs when the lesions invade the cervical tissue, and is graded from stage I to IV, depending on how far the cancer has spread beyond the cervix into surrounding tissue or organs.

Cervical cancer does not usually develop until decades after acquisition of infection with an oncogenic (cancer-causing) HPV serotype. Persistent HPV infection is detected in almost all women with cervical cancer.

HPV infection, while essential for the development of cervical cancer, is not, by itself, sufficient. Other factors have been described that may be associated with HPV persistence and high-grade lesions including smoking, early onset sexual activity, older age, contraceptive use, multiple sexual partners and genetic factors.17, 18

9.2.3 Other cancers

The clinical features of other HPV-associated cancers and their precancerous lesions in the anogenital and oropharyngeal regions vary, and also depend on the anatomical site.19 The progression from HPV‑associated precancer lesions to cancers in these sites is less well understood than the process in the cervix.

Oropharyngeal cancers

Oropharyngeal cancers include cancers of the soft palate, walls of the pharynx, the tonsils and the base of the tongue. The risk factors for oropharyngeal cancer are similar to those for cervical cancer, including the number of sexual partners, younger age at first sexual intercourse, practice of oral sex, history of genital warts and younger age.20

9.2.4 Genital warts

HPV6 and 11 account for around 90 percent of all genital warts cases. The majority of warts cases are self-limited, although some may persist for several years. Persistence is more common in patients with impaired cell-mediated immunity.1

9.2.5 Respiratory papillomatosis

Perinatal transmission of HPV virus (usually HPV types 6 or 11) can cause laryngeal infection in infants, which in rare cases can result in recurrent respiratory papillomatosis in children. Respiratory papillomatosis is characterised by multiple warty growths on the mucosal surface of the respiratory tract, which can significantly obstruct the airways.19

9.3 Epidemiology

9.3.1 Global burden of disease

HPV is an important international carcinogenic infection. The 12 high-risk types are reported to be the second most common infectious cause of cancer worldwide after Helicobacter pylori.21

Onset of sexual activity

Most HPV infections occur within the first two years of onset of sexual activity, with more than 40 percent becoming infected during this period. The first sexual relationship carries a substantial risk.22

Cervical cancer

Persistent HPV infection can lead to high-grade CIN. A 2010 study reported more than a quarter (26.7 percent; 95% CI: 21.1–31.8) of those with persistent HPV16 and nearly one in five (19.1 percent; 95% CI: 10.4–27.3) of those with persistent HPV18 develop CIN3 or cancer within 12 years.23 Approximately one-third of CIN3 progresses to invasive cervical cancer within 10 to 20 years.

Cervical cancer is the fourth cause of female cancer in the world. In higher-income countries, it is the second most common cause of female cancer in women aged 15–44 years;24 with an incidence of approximately 10–15 per 100,000 women aged 20–70 years and an annual mortality of approximately 5–8 per 100,000.

Other HPV-related cancers

HPV types 16, 18, 31, 33, 45, 52 and 58 are linked to other cancers in women and men, including vulval, vaginal, penile, anal and oropharyngeal cancers (see Table 9.1).

Anal cancers

Anal cancer remains relatively rare compared to other cancers but the global incidence has increased among both men and women, particularly in high-income regions (the average worldwide incidence is 1 per 100,ooo population).24 Women have a higher incidence of anal cancer than men. The incidence is highest among men who have sex with men, women with history of cervical or vulvar cancer, and immunosuppressed populations, including those who are HIV-infected and patients with a history of organ transplantation.24

Oropharyngeal cancers

There has been an increase in the incidence of head and neck cancers over the past few decades. This increase is mainly due to an unexpected increase in HPV-related oropharyngeal cancers, primarily in males aged 40 to 55 years with exposure to alcohol and tobacco.25

There is wide variability in the reported proportions of oropharyngeal cancers associated with HPV, ranging from 12 to 63 percent, and a lower proportion of oral cancers.19 Of the oropharyngeal cancers that are HPV‑positive, most are associated with HPV types 16 and/or 18 (see Table 9.1).

Genital warts

Genital warts, which are most commonly due to infection with HPV6 or HPV11, have a prevalence of approximately 1 percent of adults in the US.26, 27 In Scandinavian countries the reported rates are as high as 10 percent.28

9.3.2 New Zealand epidemiology

Onset of sexual activity

Data from the Youth’12 survey29, 30 suggests that approximately 8 percent of New Zealand adolescents may have had sexual intercourse before the age of 13 years. This increases to 24 percent by the age of 15 years and 46 percent by age 17 years.

Compared to 2001, students were more likely to delay sexual debut in 2012 but less likely to use condoms and contraception consistently.31 Māori (OR 0.7; 95% CIs: 0.6–0.8) and Pacific (OR 0.5; 95% CIs:
0.4–0.7) students used condoms less frequently than NZ European students; those from socioeconomically deprived communities (school decile 1) used condoms less frequently (OR 0.7; 95% CIs: 0.5–0.9) than students from wealthier communities (decile 10).31

Cervical cancer
HPV prevalence in precancerous lesions and invasive cervical cancer

The prevalence of HPV infection and distribution of HPV types among New Zealand women with histologically confirmed CIN 2/3 32, 33 or invasive cervical cancer34 is broadly consistent with that seen internationally. In women with histologically confirmed CIN 2/3, 97 percent (95% CI: 94–98) were HPV-positive and the prevalence of any high-risk HPV was 96 percent (95% CI: 91–99).32 In women with histologically confirmed invasive cervical cancer, 88.5 percent (95% CI: 83.7–92.4) were HPV-positive, and the prevalence of any high-risk HPV was 87.2 percent (95% CI: 82.2–91.3).34 For both CIN 2/3 and invasive cervical cancer, the overall distribution of HPV types was similar in Māori and non-Māori women, with HPV16 being the most commonly detected HPV type in both groups.32, 34

Cervical cancer registrations and deaths

In 2015 there were 138 new cervical cancer registrations, down from 143 in 2014 (provisional data).35 The age-standardised registration rate was 5.3 per 100,000 population, similar to the 2014 rate (5.5 per 100,000). The registration rate for Māori women was 9.7 per 100,000, 2.1 times greater than for non-Māori women (4.7 per 100,000).

The most recent cervical cancer mortality data is from 2014, when there were 46 deaths (1.4 deaths per 100,000 population).36 The mortality rate for Māori women was 3.0 per 100,000, 2.7 times greater than for non-Māori women (1.1 per 100,000).

Other HPV-related cancers

The most recent New Zealand data available for other HPV-related cancers is from 2014 (see Table 9.2). Note that this data is for new cancer registrations only; the tumours have not been analysed for the presence of HPV.

Table 9.2: Number and age-standardised rate of new registrations for other HPV-related cancers in New Zealand, 2014
Anatomic site* Number of new registrations Rate of new registrations
(per 100,000)
Vulva 70 2.0
Vagina 20 0.5
Penis 16 0.5
Anus    
  • women
54 1.5
  • men
32 1.1
Oropharynx    
  • women
4 0.1
  • men
16 0.6
Tonsils    
  • women
13 0.4
  • men
57 1.9

*     ICD codes: Vulva C51; Vagina C52; Penis C60; Anus C21; Oropharynx C10; Tonsils C09. (Note that in Table 9.1, the US definition for oropharyngeal cancer combines multiple cancers into the definition, using 4-character ICD codes. At the time of writing, New Zealand data for 2014 was only available at the 3-character ICD code level.)

Source: Ministry of Health. 2016. New cancer registrations 2014. URL: http://www.health.govt.nz/publication/new-cancer-registrations-2014 (accessed 8 February 2017).

Anal cancers

For the period 2003–2007, the age-standardised rate for anal cancer was 0.5 and 1.1 per 100,000 persons per year among men and women in New Zealand, respectively.24 In 2015 the rate increased to 1.1 per 100,000 for men and 1.5 for women (see Table 9.2).

Oropharyngeal cancers

A retrospective review of New Zealand cancer registry data for the period 1981–2010 showed a rapid rise in oropharyngeal cancers in men (mainly in those aged 40 years or older), particularly from 2005 onwards.37 The rate of oropharyngeal cancers was almost four times greater in men (1.87 per 100,000) than in women (0.47 per 100,000). The incidence rates for oral cavity cancer, which is generally associated with alcohol and tobacco consumption, remained relatively stable in both sexes during that time period. (Note that in this study, oropharyngeal cancers included cancers coded as: C01.9, C02.4, C09.0–C09.9, C14.2 and C10.0–C10.9; oral cavity cancers included: C02.0–C02.3, C02.8, C02.9, C03.0–C03.9, C06.0–C06.2, C04.0–C04.9, C05.0–C05.9, C06.8, C06.9 and C00.3–C00.5).

Genital warts

Sexually transmitted infections (STIs) are not notifiable in New Zealand. ESR cautions that the number of cases of STIs reported through the clinic-based surveillance system likely underestimates the true burden of disease in New Zealand because a substantial percentage of STIs are diagnosed by other health care providers.

From 200938 to 201539 genital warts clinical case counts reported by sexual health clinics decreased by 54.3 percent (from 3,290 to 1,504 cases) and case counts reported by family planning clinics decreased by 65.6 percent (from 546 to 188 cases). In sexual health clinics there was a decrease in diagnoses in all ethnic groups, except ‘Other’ ethnicity. In family planning clinics, the number of diagnoses decreased in every ethnic group.

In sexual health clinics, the decrease was most notable in the 15–19 years and 20–24 years age groups, and a moderate decrease in the 25–29 years age group, in both sexes (Figure 9.1). The decrease seen in older age groups, and in males, suggests that immunisation is also providing some herd immunity to unvaccinated individuals. A decline in the number of prescriptions for treating genital warts (imiquimod and podophyllum resin-based products) supports this evidence for a herd immunity effect.40 The largest decline was seen in women aged under 20 years.

Figure 9.1: Number of genital warts (first presentation) in sexual health clinics, by sex and age group, 2009–2015
Figure 9.1: Number of genital warts (first presentation) in sexual health clinics, by sex and age group, 2009–2015

Source: ESR

9.4 Vaccines

9.4.1 Available vaccines

Two HPV vaccines are approved for use (registered) and are available for distribution (marketed) in New Zealand: HPV9 (Gardasil 9, Seqirus/MSD) and HPV4 (Gardasil, Seqirus/MSD).

Both vaccines are registered for use in females aged 9–45 years and in males aged 9–26 years. HPV9 is registered as a two- or three-dose schedule in individuals aged 14 years and under, and as a three-dose schedule in older individuals. HPV4 is registered as a three-dose schedule for all age groups, but may be used as a two-dose schedule for those aged 9–14 years.

Both vaccines contain HPV virus-like particles (VLPs), which are composed of the L1 protein (a component of the virus outer layer) aggregated into clumps that mimic the outer structure of the HPV virion. The VLPs do not contain viral DNA and are incapable of causing infection. The L1 proteins are produced by genetically engineered yeast cells.

Funded HPV vaccine
Other vaccine

HPV4 was the vaccine used prior to the 1 January 2017 introduction of HPV9 (see also section A1.3.4 in Appendix 1 for the history of HPV vaccines in New Zealand).

Each 0.5 mL dose of HPV4 vaccine contains:

The vaccine does not contain any preservative or antibiotics.

9.4.2 Efficacy and effectiveness

The efficacy of HPV vaccines can only be studied in older age groups due to the sexual naivety of the younger age group; protection against persistent HPV infection and related disease is the main target for vaccination. Immunological bridging is therefore used to infer efficacy in the younger age group; that is, by comparing the antibody responses (immunogenicity) between the younger and older age groups. Because the antibody responses are non-inferior to those seen in older age groups, efficacy is inferred for the younger age group.

Immunogenicity

Although there is no known correlate of protection (that is, the antibody level required for protection against HPV-related disease), HPV vaccines generate excellent antibody responses in most recipients.

HPV4

Immunisation with three doses of HPV4 vaccine produces antibody responses against HPV16, HPV18, HPV6 and HPV11 in more than 99 percent of vaccine recipients. The height of the antibody titres following three doses of HPV vaccine is greater than that following natural infection.

Differences in seroconversion rates and antibody titres were seen in immunocompromised individuals. The immune response to HPV4 among immunocompromised children appears adequate,41, 42 although antibody titres were lower than those in healthy children of the same age groups.41 Seroconversion among HIV-infected individuals has been demonstrated to be robust and higher among those with lower HIV loads or on antiretroviral therapy.43, 44, 45

While some immunosuppression regimes can attenuate the immune response to HPV4, patients with autoimmune diseases generally appear to respond well to the vaccine.46 In contrast, adult solid organ transplant recipients produce suboptimal responses to HPV4.47

The immunogenicity of three doses of HPV4 vaccine has been established to be robust and long-lasting.48, 49, 50 Anamnestic responses have been demonstrated out to 8.5 years.

Two doses of HPV4 are more immunogenic in recipients aged between 9 and 15 years than in older age groups and comparable to three doses in older recipients.51 In young females, two doses have been found to be non-inferior to three doses, particularly when the interval between doses is at least six months.52

HPV9

The immunogenicity of HPV9 was initially assessed in women aged
16–26 years.53 Antibody responses generated by the HPV9 vaccine to HPV types 6, 11, 16 and 18 were non-inferior to those generated by the HPV4 vaccine. HPV9 has also demonstrated non-inferiority to HPV4 in girls and boys aged 9–15 years.54

Antibody responses to all nine vaccine HPV types in girls and boys aged 9–15 years and men aged 16–26 years were non-inferior to women aged 16–26 years.55, 56

Men who have sex with men appear to produce lower antibody titres than heterosexual men (although seroconversion rates to all nine vaccine types were greater than 99 percent in both groups).55 This lower antibody response is possibly due to greater exposure to the virus, highlighting the importance of vaccination at a young age.

The immunogenicity of two doses of HPV9 in girls and boys aged 9–14 years was compared with three doses in women aged 16–26 years,57 the age group in which efficacy was demonstrated. Antibody responses in girls and boys after two HPV9 doses were non-inferior to the antibody responses in women who received three doses.

Efficacy
HPV-related cancers

No studies have yet been undertaken to look for protection against invasive cervical cancer because these would require extremely long periods of follow-up and because study participants who develop precancerous lesions (CIN 2/3 or adenocarcinoma in situ) require treatment to prevent progression to invasive cancer. However, protection against CIN 2/3 or adenocarcinoma in situ is widely accepted as a surrogate for protection against invasive cancer. Bivalent and quadrivalent HPV vaccines have been shown to be highly effective in preventing these HPV16- and HPV18-related precancerous lesions in females.2, 58 In the pivotal efficacy trial in women aged 15–26 years,59 HPV4 vaccine efficacy for the prevention of precancerous lesions related to HPV16 or HPV18 was 98 percent (95% CI: 26–58) in the per-protocol susceptible population.

Studies in males, including men who have sex with men, have shown that HPV4 vaccine is efficacious against anal HPV infection and associated precancerous lesions.6, 60, 61

HPV9 efficacy was studied in women aged 16–26 years and compared with HPV4.53 HPV9 prevented cervical, vulvar and vaginal disease and persistent infection related to HPV types 31, 33, 45, 52 and 58 (the five additional serotypes in HPV9). The antibody response and incidence of disease related to HPV types 6, 11, 16 and 18 were similar in the two vaccine groups.

Effectiveness

A 2016 systematic review of published literature62 summarised the global experiences with HPV4 from 1 January 2007 to 29 February 2016. It assessed the global effect of HPV4 vaccine on HPV infection, genital warts and cervical abnormalities based on 57 publications across nine countries. The greatest impact was seen in countries with high vaccine uptake and among girls vaccinated prior to HPV exposure. Maximal reductions of around 90 percent were reported for vaccine-type HPV infections (6, 11, 16, 18) and genital wart cases.

Duration of protection

As vaccination programmes have only been in place for a maximum of 10 years, the duration of protection is not yet known. Follow-up studies 8–10 years after HPV vaccination have shown no waning of protection.2 Long-term studies are ongoing to determine the duration of efficacy for all HPV vaccines.

Herd immunity

Australia has seen a reduction in the prevalence of vaccine-type HPV infections (6, 11, 16, 18) in unvaccinated young men after the introduction of the vaccine to young women, supporting the role of herd immunity.63, 64, 65 There was also a significant decrease in the prevalence of vaccine-type HPV infections in unvaccinated women (aged 25 years or younger).66

In a study of data from a sexual health clinic in Melbourne,65 the researchers noted the near disappearance of genital warts in women and heterosexual men aged under 21 years. In addition, the data indicated that the basic reproductive rate (see section 1.2.1) had fallen below one. This reduction in cases occurred without any corresponding reduction in women aged over 30 years, men who have sex with men, and non-residents. Similar trends were noted in the data from the Australian genital warts national surveillance network.

Previous exposure to HPV

While efficacy is unclear, there are no safety concerns in offering vaccination to women who have had HPV-related disease and would like to use the vaccine to reduce the risk of further disease.

A retrospective analysis of the HPV4 vaccine’s pivotal efficacy trial data (Future I and Future II) studied a group of women who were vaccinated before they had their first treatment for HPV-related disease.67 This showed a reduction in subsequent HPV-related disease in vaccinated women aged 15–26 years who had received treatment for cervical, vulvar or vaginal disease during the trial. The study showed a 46.2 percent reduction (95% CI: 22.5–63.2) after cervical surgery of any HPV-related disease and 35.2 percent reduction (95% CI: 18.8–51.8) after diagnosis of genital warts or vaginal or vulvar disease.

In contrast, a systematic review68 explored efficacy against CIN3+ precancers in women with evidence of prior vaccine-type HPV exposure in three randomised controlled trials and two post-trial cohort studies and showed no evidence that HPV vaccines were effective in preventing vaccine-type HPV-associated precancer in pre-exposed women. Despite these findings, it was concluded that longer-term benefits in preventing re-infection could not be excluded; ie, the vaccine is not therapeutic but may prevent future infection, emphasising the importance of vaccination prior to sexual debut.

International recommendations

The WHO recommends a two- or three-dose HPV4 schedule for individuals aged under 15 years and a three-dose schedule for older individuals.69

HPV9 was registered for use as a two- or three-dose schedule for individuals aged under 15 years and a three-dose schedule for older individuals by the European Medicines Agency70 in June 2015 and by the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) in July 2016.

Since October 2016, the US Advisory Committee on Immunization Practices has recommended a two-dose HPV schedule for individuals aged 9–14 years and a three-dose schedule for those aged 15–26 years or who are immunocompromised.

9.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.71 Store in the dark at +2°C to +8°C. Do not freeze.

9.4.4 Dosage and administration

The dose of HPV vaccine is 0.5 mL, administered by intramuscular injection in the deltoid area (see section 2.2.3).

Co-administration with other vaccines

HPV vaccine may be co-administered with any live or inactivated vaccine indicated at the same visit.2

Interchangeability

All HPV vaccines may be used interchangeably for completion of a course.72

9.5 Recommended immunisation schedule

9.5.1 Recommended and funded

From 1 January 2017 males and females aged 26 years and under become eligible for HPV vaccine. Including males in a routine vaccination programme is expected to increase the benefit to the population in terms of reduction for both HPV-related cancer outcomes and genital warts.

See Table 9.3 for HPV vaccine recommendations and schedules. Children aged 14 years and under receive two doses of HPV vaccine, at 0 and 6–12 months – provided the second dose is administered before their 15th birthday, see Table 9.3 below. However, three doses are required for this age group if they have confirmed HIV infection or are transplant or chemotherapy patients, or if the minimum dosing interval is not met (see below). Older individuals receive three doses of HPV vaccine, at 0, 2 and 6 months.

Table 9.3: HPV vaccine recommendations and schedules

Note: HPV vaccine may be offered from age 9 years, but the usual Schedule will be at age 11/12 years (school years 7/8). Funded recommendations are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to the funding decisions.

Recommended and funded Doses HPV Schedulea
Children aged 14 years and under 2b 0 and 6–12c months
Individuals aged 15–26 yearsd,e 3 0, 2 and 6 monthsf
Individuals aged 9–26 years: 3 0, 2 and 6 months
  • with confirmed HIV infectiong
  • transplant (including stem cell) patientsg
  • post-chemotherapy patientsg
An additional dose At least 1 month after the last dose
Recommended but not funded Doses HPV Schedule

Individuals aged 27 years and older:d,e,h

  • who have had little previous exposure to HPV and are now likely to be exposed
  • who are men who have sex with men
  • with HIV.
3 0, 2 and 6 monthsf
  1. Individuals who started with HPV4 may complete their remaining doses with HPV9. Those who were fully vaccinated with HPV4 are not eligible for HPV9.
  2. Regardless of the age at the 1st dose, if the 2nd HPV dose is given at age 15 years or older a 3rd HPV dose is recommended and funded. Give the 3rd HPV dose at least 4 months after the 2nd.
  3. For children aged 14 years and under, the 2nd dose is preferably given at least 6 months after the 1st. However, if the 2nd dose is given less than 5 months after the 1st, a 3rd HPV dose is recommended and funded. Give the 3rd HPV dose at least 6 months after the 1st.
  4. The decision to vaccinate older age groups should follow an assessment of the potential benefits of vaccination – based on their likely previous HPV exposure and future risks.
  5. Individuals who were under age 27 years when they commenced HPV vaccination are currently funded to complete the 3-dose course, even if they are older than 27 years when they complete it.
  6. If a shortened schedule is required, give the 2nd dose at least 1 month after the 1st dose and the 3rd dose at least 3 months after the 2nd dose.
  7. See section 4.3.3 for more information.
  8. HPV vaccines are registered for use in females aged 9–45 years and in males aged
    9–26 years. However, there are no theoretical concerns that the efficacy or safety of HPV vaccine in males up to the age of 45 years will differ significantly from females of the same age or younger males.

Immunisation should be completed before the onset of sexual activity. The optimal time for HPV administration is at age 9–13 years, as most males and females in this age group would be naïve to all HPV types. However, individuals who have begun sexual activity may still benefit from vaccination. The decision to vaccinate older age groups should follow an assessment of the potential benefits of vaccination – based on their likely previous HPV exposure and future risks.

Note:

9.5.2 Recommended but not funded

Individuals aged 27 years and older

The decision to vaccinate older age groups should follow an assessment of the potential benefits of vaccination – based on their likely previous HPV exposure and future risks.

The data from the pivotal studies for HPV4 has demonstrated potential benefit to some women older than 25 years. HPV4 has been shown to be effective at preventing infection and disease from the vaccine types in women aged 24–45 years who were uninfected at baseline.73 However, pre-vaccination testing for cervical cytological abnormalities or for HPV infection is not recommended.

HPV9 and HPV4 vaccines are registered for use in females aged 9–45 years and in males aged 9–26 years. However, there are no theoretical concerns that the efficacy or safety of HPV vaccine in males up to the age of 45 years will differ significantly from females of the same age or younger males.

9.5.3 Pregnancy and breastfeeding

HPV vaccines are not recommended for pregnant women; however, enquiring about the possibility of pregnancy is not necessary before vaccination.74

Data to date shows no adverse effects of HPV vaccines on pregnancy outcomes.2, 75 However, if a vaccine dose has been administered around the time of conception or during pregnancy, health professionals are advised to report this to CARM (see section 1.6.3) and the vaccine manufacturer to assist with ongoing safety monitoring. If a woman is found to be pregnant after starting the HPV vaccine schedule, the remaining doses should be delayed until after pregnancy.

HPV vaccines may be given to breastfeeding women.19

9.6 Contraindications and precautions

See section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

9.6.1 Contraindications

HPV vaccine should not be administered to people with a history of an anaphylactic reaction to a prior dose of HPV vaccine or to a vaccine component. HPV vaccines contain HPV proteins produced by genetically engineered yeast cells. They should not, therefore, be given to people with a history of an immediate hypersensitivity to yeast.

9.6.2 Precautions

Pregnancy is a precaution – see section 9.5.3.

9.7 Expected responses and AEFIs

HPV vaccines have excellent safety profiles internationally. There have been no safety signals raised since the vaccines were licensed, and a number of large investigations have been carried out to assess specific outcomes, particularly autoimmune conditions.76, 77, 78, 79, 80 Post‑marketing surveillance systems globally continue to monitor the safety of HPV vaccination programmes.81, 82, 83 The WHO’s Global Advisory Committee on Vaccine Safety has systematically reviewed HPV vaccine safety and has not found any safety issue that would alter its recommendations for use.84 The main challenge with HPV vaccine is communicating its excellent safety profile.85 (See also the HPV discussion in section 3.2.4.)

Syncope (fainting) occurs frequently in adolescents following vaccination, but this is an injection reaction, not a reaction to the vaccine.1, 86

Safety has been evaluated in approximately 15,000 subjects in the HPV9 clinical development programme.72 The vaccine is well-tolerated, and most adverse events were injection site-related pain, swelling, and erythema that were mild to moderate in intensity. The safety profiles were similar in HPV4 and HPV9 vaccinees. Female HPV9 recipients had more injection site adverse events than female HPV4 recipients, including swelling (40.3 percent compared to 29.1 percent in HPV4 recipients) and erythema (34 percent compared to 25.8 percent in HPV4 recipients). Injection site adverse events were similar in males following either vaccine. Male recipients had fewer injection site adverse events. Rates of injection-site swelling and erythema both increased following each successive dose of HPV9.

In summary, HPV9 is well-tolerated in all age groups, although it is slightly more reactogenic than HPV4.53, 55, 72 The most common adverse events are pain, swelling, erythema, pruritus, headache and pyrexia.

9.8 Cancer prevention measures

For women, HPV immunisation is part of a three-pronged approach to cervical cancer prevention that also includes regular cervical screening and safer sex approaches. For men, HPV immunisation and safer sex approaches are expected to contribute to the prevention of HPV-related cancers and disease that affect men, as well as cervical cancer prevention in women.

9.8.1 HPV immunisation

A vaccine that can prevent infection with oncogenic HPV types has the potential to reduce the incidence of precursor lesions and cancer. Vaccination needs to be administered before HPV infection occurs in order to prevent atypia and malignancy. Because genital HPVs are so common and so readily transmitted, in practical terms vaccination should be offered before the onset of sexual activity; that is, during early adolescence.

HPV immunisation does not reduce the progression of established disease but can be used in therapeutic situations by preventing the reactivation of latent infection.

9.8.2 Regular cervical screening for women

A successful HPV immunisation programme for men and women will reduce the community prevalence of HPV infection and thus the incidence of cervical cancer in women. However, HPV immunisation will not completely eliminate cervical cancer because some women will not have been vaccinated, a few will not develop immunity despite vaccination, and some will be infected prior to vaccination or with oncogenic types not present in the vaccine.

Consequently, women will need to continue to undergo regular cervical screening to detect those precancerous lesions that occur despite vaccination. Cervical screening programmes are based on regular cytological screening or HPV testing to detect, monitor and treat at an early stage precancerous lesions, or CIN. These programmes have been successful in reducing invasive disease and mortality.

9.8.3 Safer sex approaches

To minimise the risk of HPV infection (plus other sexually transmitted infections), practitioners should remind individuals of safer sex approaches, including sexual abstinence, monogamous relationships, delayed sexual debut, and minimising the number of sexual partners.2 Consistent and correct use of condoms can decrease the risk of anogenital HPV infection when infected areas are covered or protected by the condom. However, HPV transmission in the genital region may occur even when condoms are used and does not necessarily require penetrative intercourse.

9.9 Variations from the vaccine data sheets

HPV vaccines are registered for use in females aged 9–45 years and in males aged 9–26 years. However, there are no theoretical concerns that the efficacy or safety of HPV vaccine in males up to the age of 45 years will differ significantly from females of the same age or younger males (see section 9.5.2).

For the three-dose schedules, the HPV vaccine data sheets recommend that all three doses are given within a 12-month period. The Ministry of Health recommends that if the three-dose schedule has been interrupted, prior doses do not need to be repeated regardless of how long ago the previous doses were given (see Appendix 2).

The HPV9 data sheet states that there are no studies on the interchangeability of HPV vaccines. The Ministry of Health recommends that all HPV vaccines may be used interchangeably for completion of a course.72 Those individuals who started with HPV4 may complete their remaining doses with HPV9.

References

  1. Schiller JT, Lowy DR, Markowitz LE. 2013. Human papillomavirus vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  2. American Academy of Pediatrics. 2015. Human papillomaviruses. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  3. Saraiya M, Unger ER, Thompson TD, et al. 2015. US assessment of HPV types in cancers: Implications for current and 9-valent HPV vaccines. Journal of the National Cancer Institute 107(6). DOI: 10.1093/jnci/djv086 (accessed 14 September 2016).
  4. Ministry of Health. 2007. High Grade Squamous Intra-epithelial Lesions (HSIL) in New Zealand. URL: https://www.nsu.govt.nz/system/files/resources/hsil-in-new-zealand.pdf (accessed 10 December 2013).
  5. McFadden K, McConnell D, Salmond C, et al. 2004. Socioeconomic deprivation and the incidence of cervical cancer in New Zealand:
    1988–1998. New Zealand Medical Journal 117(1206): U1172.
  6. Giuliano AR, Palefsky JM, Goldstone S, et al. 2011. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. [Erratum appears in New England Journal of Medicine 2011; 364(15): 1481.] New England Journal of Medicine 364(5): 401–11.
  7. Centers for Disease Control and Prevention. 2012. Human papillomavirus-associated cancers – United States, 2004–2008. Morbidity and Mortality Weekly Report 61(15): 258–61. URL: www.cdc.gov/mmwr/preview/mmwrhtml/mm6115a2.htm (accessed 3 September 2013).
  8. Smith JS, Gilbert PA, Melendy A, et al. 2011. Age-specific prevalence of human papillomavirus infection in males: a global review. Journal of Adolescent Health 48(6): 540–2.
  9. Malachek DA, Poynten M, Jin F, et al. 2012. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncology 13(5): 487–500.
  10. Zou H, Tabrizi SN, Grulich AE, et al. 2014. Early acquisition of anogenital human papillomavirus among teenage men who have sex with men. Journal of Infectious Diseases 209(5): 642–51.
  11. Vajdic CM, van Leeuwen MT, Jin J, et al. 2009. Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men. Sexually Transmitted Infections 85(5): 330–5.
  12. Grulich AE, van Leeuwen MT, Falster MO, et al. 2007. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. The Lancet 370(9581): 59–67.
  13. Wilkin T, Lee JY, Lensing SY, et al. 2010. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. Journal of Infectious Diseases 202(8): 1246–53.
  14. Beachler DC, Weber KM, Margolick JB, et al. 2012. Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at‑risk HIV-negative adults. Cancer Epidemiology Biomarkers and Prevention 21(1): 122–33. DOI: 10.1158/1055-9965.epi-11-0734 (accessed 1 January 2012).
  15. Begue R. 2012. Immunization recommendations for the HIV-infected adolescent. HIV Clinician 24(2): 15–21.
  16. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-infected Adults and Adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. URL: https://aidsinfo.nih.gov/contentfiles/lvguidelines/Adult_OI.pdf (accessed 11 November 2016).
  17. Sarian LO, Derchain SF, Pitta Dda R, et al. 2004. Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ). Journal of Clinical Virology 31(4): 270–4.
  18. Safaeian M, Hildesheim A, Gonzalez P, et al. 2012. Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLOS ONE 7(4): e33619. DOI: 10.1371/journal.pone.0033619 (accessed 28 August 2013).
  19. Department of Health and Ageing. 2016. Human papillomavirus. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-6 (accessed 19 October 2016).
  20. Syrjanen S. 2010. The role of human papillomavirus infection in head and neck cancers. Annals of Oncology 21(Suppl 7): vii243–5. DOI: 10.1093/annonc/mdq454 (accessed 30 January 2017).
  21. Plummer M, de Martel C, Vignat J, et al. 2016. Global burden of cancers attributable to infections in 2012: a synthetic analysis. The Lancet Global Health 4(9): e609–16. URL: http://www.thelancet.com/journals/langlo/article/PIIS2214-109X(16)30143-7/fulltext (accessed 4 August 2016).
  22. Winer RL, Feng Q, Hughes JP, et al. 2008. Risk of female human papillomavirus acquisition associated with first male sex partner. Journal of Infectious Diseases 197(2): 279–282.
  23. Kjaer SK, Frederiksen K, Munk C, et al. 2010. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. Journal of the National Cancer Institute 102(19): 1478–88. DOI: 10.1093/jnci/djq356 (accessed 2 April 2017).
  24. Bruni L, Barrionuevo-Rosas L, Albero G, et al. 2016. Human Papillomavirus and Related Diseases in the World. Summary Report 15 December 2016. URL: http://www.hpvcentre.net/statistics/reports/XWX.pdf (accessed 30 January 2017).
  25. Mallen-St Clair J, Alani M, Wang MB, et al. 2016. Human papillomavirus in oropharyngeal cancer: the changing face of a disease. Biochimica et Biophysica Acta (BBA) – Reviews on Cancer 1866(2): 141–50. DOI: 10.1016/j.bbcan.2016.07.005 (accessed 30 January 2017).
  26. Wiley DJ, Douglas J, Beutner K, et al. 2002. External genital warts: diagnosis, treatment, and prevention. Clinical Infectious Diseases 35(Supp. 2): S210–24.
  27. Koutsky LA. 1997. Epidemiology of genital human papillomavirus infection. American Journal of Medicine 102(5A): 3–8.
  28. Kjaer SK, Tran TN, Sparen P, et al. 2007. The burden of genital warts: a study of nearly 70,000 women from the general female population in the 4 Nordic countries. Journal of Infectious Diseases 196(10): 1447–54.
  29. Clark TC, Fleming T, Bullen P, et al. 2013. Youth’12 Overview: The health and wellbeing of New Zealand secondary school students in 2012. URL: https://www.fmhs.auckland.ac.nz/assets/fmhs/faculty/ahrg/docs/2012-overview.pdf (accessed 24 October 2013).
  30. Clark TC, Fleming T, Bullen P, et al. 2013. Youth’12 Prevalence Tables: The health and wellbeing of New Zealand secondary school students in 2012. URL: https://www.fmhs.auckland.ac.nz/assets/fmhs/faculty/ahrg/docs/2012prevalence-tables-report.pdf (accessed 24 October 2013).
  31. Clark TC, Lucassen MF, Fleming T, et al. 2016. Changes in the sexual health behaviours of New Zealand secondary school students, 2001–2012: findings from a national survey series. Australian and New Zealand Journal of Public Health 40(4): 329–36. DOI: 10.1111/1753-6405.12543 (accessed 11 July 2016).
  32. Kang Y-J, Lewis H, Smith MA, et al. 2015. Pre-vaccination type-specific HPV prevalence in confirmed cervical high grade lesions in the Māori and non-Māori populations in New Zealand. BMC Infectious Diseases 15(365). DOI: 10.1186/s12879-015-1034-5 (accessed 15 October 2016).
  33. Simonella LM, Lewis H, Smith MA, et al. 2013. Type-specific oncogenic human papillomavirus infection in high grade cervical disease in New Zealand. BMC Infectious Diseases 13: 114. URL: http://www.biomedcentral.com/1471-2334/13/114 (accessed 14 September 2016).
  34. Sykes P, Gopala K, Tan AL, et al. 2014. Type distribution of human papillomavirus among adult women diagnosed with invasive cervical cancer (stage 1b or higher) in New Zealand. BMC Infectious Diseases 14: 374. URL: http://www.biomedcentral.com/1471-2334/14/374 (accessed 14 September 2016).
  35. Ministry of Health. 2016. Selected Cancers 2013, 2014, 2015 (Provisional). URL: http://www.health.govt.nz/publication/selected-cancers-2013-2014-2015 (accessed 8 December 2016).
  36. Ministry of Health. 2016. Mortality 2014 Data Tables (Provisional). URL: http://www.health.govt.nz/publication/mortality-2014-data-tables (accessed 28 March 2017).
  37. Chelimo C, Elwood JM. 2015. Sociodemographic differences in the incidence of oropharyngeal and oral cavity squamous cell cancers in New Zealand. Australian and New Zealand Journal of Public Health 39(2): 162–7. DOI: 10.1111/1753-6405.12352 (accessed 14 September 2016).
  38. Institute of Environmental Science and Research Ltd. 2010. Sexually Transmitted Infections in New Zealand: Annual surveillance report 2009. URL: https://surv.esr.cri.nz/surveillance/annual_sti.php?we_objectID=2316 (accessed 17 November 2016).
  39. Institute of Environmental Science and Research Ltd. 2016. STI Clinic Surveillance: Quarterly Reports Jan–Mar 2016. URL: https://surv.esr.cri.nz/surveillance/quarterly_sticlinic.php?we_objectID=4382 (accessed 17 November 2016).
  40. Wilson N, Morgan J, Baker MG. 2014. Evidence for effectiveness of a national HPV vaccination programme: national prescription data from New Zealand. Sexually Transmitted Infections 90(2): 103. DOI: 10.1136/sextrans-2013-051037 (accessed 5 September 2016).
  41. MacIntyre CR, Shaw P, Mackie FE, et al. 2016. Immunogenicity and persistence of immunity of a quadrivalent human papillomavirus (HPV) vaccine in immunocompromised children. Vaccine 34(36): 4343–50.
  42. Gomez-Lobo V, Whyte T, Kaufman S, et al. 2014. Immunogenicity of a prophylactic quadrivalent human papillomavirus L1 virus-like particle vaccine in male and female adolescent transplant recipients. Pediatric Transplantation 18(3): 310–15.
  43. Giacomet V, Penagini F, Trabattoni D, et al. 2014. Safety and immunogenicity of a quadrivalent human papillomavirus vaccine in HIV-infected and HIV-negative adolescents and young adults. Vaccine 32(43): 5657–61.
  44. Kahn JA, Xu J, Kapogiannis BG, et al. 2013. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clinical Infectious Diseases 57(5): 735–44.
  45. Kojic EM, Kang M, Cespedes MS, et al. 2014. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clinical Infectious Diseases 59(1): 127–35.
  46. Jacobson DL, Bousvaros A, Ashworth L, et al. 2013. Immunogenicity and tolerability to human papillomavirus-like particle vaccine in girls and young women with inflammatory bowel disease. Inflammatory Bowel Disease 19(7): 1441–9. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677764/ (accessed 4 September 2016).
  47. Kumar D, Unger ER, Panicker G, et al. 2013. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. American Journal of Transplantation 13(9): 2411–7. DOI: 10.1111/ajt.12329 (accessed 4 September 2016).
  48. Joura EA, Kjaer SK, Wheeler CM, et al. 2008. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine 26(52): 6844–51.
  49. Einstein MH, Baron M, Levin MJ, et al. 2009. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18–45 years. Human Vaccines 5(10): 705–19.
  50. Rowhani-Rahbar A, Alvarez FB, Bryan JT, et al. 2012. Evidence of immune memory 8.5 years following administration of a prophylactic human papillomavirus type 16 vaccine. Journal of Clinical Virology 53(3):
    239–43.
  51. Donken R, Knol MJ, Bogaards JA, et al. 2015. Inconclusive evidence for non-inferior immunogenicity of two- compared with three-dose HPV immunization schedules in preadolescent girls: A systematic review and meta-analysis. Journal of Infection 71(1): 61–73. URL: http://dx.doi.org/10.1016/j.jinf.2015.02.005 (accessed 4 September 2016).
  52. Sankaranarayanan R, Prabhu PR, Pawlita M, et al. 2016. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. The Lancet Oncology 17(1): 67–77. URL: http://dx.doi.org/10.1016/S1470-2045(15)00414-3 (accessed 4 September 2016).
  53. Joura EA, Giuliano AR, Iversen O-E, et al. 2015. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. New England Journal of Medicine 372(8): 711–23. DOI: 10.1056/NEJMoa1405044 (accessed 4 September 2016).
  54. Vesikari T, Brodszki N, van Damme P, et al. 2015. A randomized, double-blind, phase III study of the immunogenicity and safety of a 9-valent human papillomavirus L1 virus-like particle vaccine (V503) versus gardasil in 9–15-year-old girls. Pediatric Infectious Disease Journal 34(9): 992–8. DOI: 10.1097/INF.0000000000000773 (accessed 4 September 2016).
  55. Castellsagué X, Giuliano AR, Goldstone S, et al. 2015. Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine 33(48): 6892–901.
  56. Van Damme P, Olsson S, Block S, et al. 2015. Immunogenicity and safety of a 9-valent HPV vaccine. Pediatrics 136(1): e28–39. URL: http://pediatrics.aappublications.org/content/136/1/e28 (accessed 28 August 2016).
  57. Seqirus/MSD. 2016. Gardasil 9 Data Sheet. URL: http://www.medsafe.govt.nz/profs/datasheet/g/gardasil9inj.pdf (accessed 4 September 2016).
  58. Lehtinen M, Paavonen J, Wheeler CM, et al. 2012. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. The Lancet Oncology 13(1): 89–99.
  59. FUTURE II Study Group. 2007. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New England Journal of Medicine 356(19): 1915–27.
  60. Palefsky JM, Giuliano AR, Goldstone S, et al. 2011. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. New England Journal of Medicine 365(17): 1576–85.
  61. Swedish KA, Factor SH, Goldstone SE. 2012. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clinical Infectious Diseases 54(7): 891–8.
  62. Garland SM, Kjaer SK, Muñoz N, et al. 2016. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of ten years of real-world experience. Clinical Infectious Diseases 53(4): 519–27. DOI: 10.1093/cid/ciw354 (accessed 5 September 2016).
  63. Chow EPF, Machalek DA, Tabrizi SN, et al. 2016. Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study. The Lancet Infectious Diseases 17(1): 68–77. DOI: http://dx.doi.org/10.1016/S1473-3099(16)30116-5 (accessed 28 September 2016).
  64. Donovan B, Franklin N, Guy R, et al. 2011. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. The Lancet Infectious Diseases 11(1): 39–44.
  65. Read TRH, Hocking JS, Chen MY, et al. 2011. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sexually Transmitted Infections 87(7): 544–7.
  66. Chow EPF, Danielewski JA, Fehler G, et al. 2015. Human papillomavirus in young women with Chlamydia trachomatis infection 7 years after the Australian human papillomavirus vaccination programme: a cross-sectional study. The Lancet Infectious Diseases 15(11): 1314–23. DOI: 10.1016/S1473-3099(15)00055-9 (accessed 28 September 2016).
  67. Joura EA, Garland SM, Paavonen J, et al. 2012. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. British Medical Journal 344: e1401. DOI: http://dx.doi.org/10.1136/bmj.e1401 (accessed 29 October 2012).
  68. Miltz A, Price H, Shahmanesh M, et al. 2014. Systematic review and meta-analysis of L1-VLP-based human papillomavirus vaccine efficacy against anogenital pre-cancer in women with evidence of prior HPV exposure. PLoS ONE 9(3): e90348. DOI: 10.1371/journal.pone.0090348 (accessed 24 September 2016).
  69. World Health Organization. 2014. Human papillomavirus vaccines: WHO position paper, October 2014. Weekly Epidemiological Record 89(43): 465–92. URL: http://www.who.int/wer/2014/wer8943.pdf?ua=1 (accessed 4 September 2016).
  70. European Medicines Agency. 2016. Gardasil 9: EPAR Summary for the Public. URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003852/WC500189114.pdf (accessed 5 September 2016).
  71. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  72. Centers for Disease Control and Prevention. 2015. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. Morbidity and Mortality Weekly Report 64(11): 300–4. URL: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm (accessed 26 August 2016).
  73. Muñoz N, Manalastas R, Pitisuttithum P, et al. 2009. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. The Lancet 373(9679): 1949–57.
  74. Bonde U, Joergensen JS, Lamont RF, et al. 2016. Is HPV vaccination in pregnancy safe? Human Vaccines & Immunotherapeutics 12(8): 1960–4.
  75. Moreira ED Jr, Block SL, Ferris D, et al. 2016. Safety profile of the 9-valent HPV vaccine: a combined analysis of 7 phase III clinical trials. Pediatrics 138(2): e20154387. DOI: 10.1542/peds.2015-4387 (accessed 18 October 2016).
  76. Chao C, Klein NP, Velicer CM, et al. 2012. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. Journal of Internal Medicine 271(2): 193–203. DOI: 10.1111/j.1365-2796.2011.02467.x (accessed 29 October 2012).
  77. Arnheim-Dahlstroem L, Pasternak B, Svanstroem H, et al. 2013. Autoimmune, neurological and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. British Medical Journal 247: f5906. DOI: 10.1136/bmj.f5906 (accessed 10 December 2016).
  78. Grimaldi-Bensouda L, Guillemot D, Godeau B, et al. 2014. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. Journal of Internal Medicine 275(4): 398–408. DOI: 10.1111/joim.12155 (accessed 10 December 2016).
  79. Langer-Gould A, Qian L, Tartof SY, et al. 2014. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating disease. JAMA Neurology 71(12): 1506–13. DOI: 10.1001/jamaneurol.2014.2633 (accessed 10 December 2016).
  80. Scheller NM, Svanström H, Pasternak B, et al. 2015. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating disease of the central nervous system. Journal of the American Medical Association 313(1): 54–61. DOI: 10.1001/jama.2014.16946 (accessed 10 December 2016).
  81. Nguyen M, Ball R, Midthun K, et al. 2012. The Food and Drug Administration’s post-licensure rapid immunization safety monitoring program: strengthening the federal vaccine safety enterprise. Pharmacoepidemiology and Drug Safety 21(Suppl 1): 291–7. DOI: 10.1002/pds.2323 (accessed 26 December 2012).
  82. Kliewer EV, Demers AA, Brisson M, et al. 2010. The Manitoba human papillomavirus vaccine surveillance and evaluation system. [Erratum appears in Health Reports 2010; 21(3): 77.] Health Reports 21(2): 37–42.
  83. Gold MS, McIntyre P. 2010. Human papillomavirus vaccine safety in Australia: experience to date and issues for surveillance. Sexual Health 7(3): 320–4.
  84. World Health Organization. 2013. Global Advisory Committee on Vaccine Safety, 12–13 June 2013. Weekly Epidemiological Record 88(29): 301–12. URL: www.who.int/vaccine_safety/committee/reports/wer8829.pdf (accessed 4 November 2013).
  85. World Health Organization. 2016. Meeting of the Strategic Advisory Group of Experts on Immunization, April 2016 – conclusions and recommendations. Weekly Epidemiological Record 91(21): 266–84. URL: http://www.who.int/wer/2016/wer9121.pdf?ua=1 (accessed 12 October 2016).
  86. Klein NP, Hansen J, Chao C, et al. 2012. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Archives of Pediatrics and Adolescent Medicine 166(12): 1140–8. DOI: 10.1001/archpediatrics.2012.1451 (accessed 26 December 2012).

10 Influenza

In this chapter:

Key information

10.1 Virology

10.2 Clinical features

10.3 Epidemiology

10.4 Vaccines

10.5 Recommended immunisation schedule

10.6 Contraindications and precautions

10.7 Expected responses and AEFIs

10.8 Public health measures

10.9 Variations from the vaccine data sheet

References

Key information

Mode of transmission Spread by droplets generated by sneezing and coughing, by direct or indirect contact, or by the aerosol route.
Incubation period Usually 1–3 days (range 1–7 days).
Period of communicability From 1–2 days before symptoms start until about day 5 of illness; may be longer in young children and if immunocompromised.
Disease burden Influenza epidemics occur each year. The highest burden of disease is in the very young, the elderly, pregnant women, those with co-morbid conditions, people from low income groups, and in Māori and Pacific ethnic groups.
Funded vaccines

For 2017: Trivalent inactivated split virion vaccine (Influvac).

When available: Quadrivalent inactivated split virion vaccine (Influvac Tetra).

Dose, presentation, route

Children aged 6–35 months: 0.25 mL per dose.

Individuals aged 3 years and older: 0.5 mL per dose.

Pre-filled syringe.

Intramuscular injection.

Funded vaccine indications

1 dose is recommended and funded annually for:

  • pregnant women
  • individuals aged 65 years and older
  • individuals aged 6 months to under 65 years with eligible conditions.

Children aged under 9 years who have not previously received influenza vaccine require 2 doses 4 weeks apart (funded for children with eligible conditions).

Vaccine efficacy/ effectiveness Depends on the match of the strains in the vaccine with circulating strains, the age of the individual and whether they have any underlying medical conditions.
Precautions

A history of egg anaphylaxis warrants the first dose of influenza vaccine to be given in a closely monitored environment such as a hospital or outpatient clinic.

There may be a small increased risk of fever and febrile convulsions with concomitant delivery of PCV13 and influenza vaccine in children aged 6 months to under 5 years.

Adverse events Children aged under 5 years are more likely than older children or adults to have a febrile reaction to influenza vaccine.

10.1 Virology

Influenza viruses belong to the Orthomyxoviridiae family, and are classified into influenza virus types A, B and C. Influenza A viruses include a number of subtypes, classified on the basis of two surface antigens:

Subtypes which have in the past caused pandemics include the H1N1, H2N2, H3N2 and H1N1pdm09 viruses, while the H3N2 and H1N1pdm09 viruses continue to cause epidemics as seasonal influenza viruses. Influenza B has two lineages of viruses; B/Victoria and B/Yamagata, which are also associated with outbreaks and epidemics. Influenza C is associated with mild cases of upper respiratory infection.

10.1.1 Antigenic drift

Influenza A and B viruses undergo frequent small changes (mutations) in their segmented RNA genome. The mutations that occur in the coding regions responsible for H and N surface antigens lead to ‘antigenic drift’ and the emergence of new antigenic variants or virus strains. These new strains are described by the geographic site of isolation, laboratory number and year of isolation; for example, A/Hong Kong/4801/2014 (H3N2). Because of this ongoing antigenic drift, seasonal influenza virus vaccine formulations are reviewed by the WHO bi-annually.

10.1.2 Antigenic shift

Novel influenza A virus subtypes have emerged periodically in the past which have caused pandemics in humans. The mixing of the genomic segments of two or more influenza A viruses leads to a new virus subtype with novel H and N surface antigens and is known as ‘antigenic shift’. The emergence of novel viruses through the adaptation of avian influenza viruses to humans and the re-assortment of the genomic segments of multiple viruses, ie, human, avian and pig influenza viruses, are also recognised as possible mechanisms.

10.2 Clinical features

Influenza is contagious, with a reproductive number estimated at 1.4–41 (see section 1.2.1). The virus is transmitted by respiratory droplets generated by sneezing and coughing that land directly on the respiratory mucous membranes, by direct or indirect contact (contaminated hands or fomites), or by the aerosol route.2

The incubation period can range from one to seven days (average one to three days), during which time the virus replicates in the ciliated columnar epithelial cells of the upper and lower respiratory tract. An infected person is contagious from one to two days before symptoms start until about day five of the illness. Peak viral shedding occurs one to three days after the development of symptoms, diminishing to low levels by five days. Children shed more virus and remain infectious for longer than adults.

In older children and adults the illness characteristically begins abruptly with fever and a variety of clinical symptoms, including chills, malaise, headache, myalgia, non-productive cough, rhinitis, sore throat and mild conjunctivitis. Vomiting and diarrhoea may be present. While children aged under 5 years have fever, cough and rhinitis, infants may present with rhinitis only.

There is a wide range of symptoms, from asymptomatic to severe disease. Mild influenza is common and symptoms can be non-specific, resulting in a large proportion of undetected influenza infections.

In the young, influenza virus may cause croup, bronchiolitis and pneumonia. Fever is often less evident in the elderly. Influenza typically resolves after several days in the majority of people, although cough and malaise may persist for two or more weeks.

Infections due to pandemic influenza A strains are more likely to lead to severe morbidity and increased mortality than influenza B or seasonal influenza A strains.

In some people, influenza can exacerbate underlying medical conditions, such as pulmonary, cardiac or metabolic disease. Some of the many reported complications associated with influenza include pneumonia, respiratory failure, myositis, encephalopathy, myocarditis, pericarditis, Reye syndrome (associated with aspirin use in children), bronchitis, otitis media and death.

10.3 Epidemiology

10.3.1 Global epidemiology

Influenza is an important cause of disease worldwide. Annual epidemics are estimated to result in about 3 to 5 million cases of severe illness, and about 250,000 to 500,000 deaths globally.3

In temperate climates, seasonal epidemics occur mainly during winter, while in tropical regions, influenza may occur throughout the year, causing outbreaks more irregularly.3

From time to time, pandemics occur when a new virus arises and spreads globally (see section 10.3.3). The last pandemic was caused by the A(H1N1)pdm09 virus. More than 214 countries and overseas territories reported laboratory-confirmed influenza, including over 18,449 deaths.4

10.3.2 New Zealand epidemiology

New Zealand experiences the typical temperate climate epidemiology of influenza, with the peak incidence occurring during the winter months, however influenza activity may occur throughout the year.

The impact of influenza in New Zealand is substantial in terms of general practice consultations, hospitalisations and deaths. The highest burden of disease is in the very young, the elderly, pregnant women, those with co-morbid conditions, people from low income groups, and Pacific and Māori ethnic groups.

For detailed information, including influenza surveillance and influenza reports, see the ESR website (https://surv.esr.cri.nz/virology/virology.php). Note that at the time of writing, only influenza-like illness and vaccine uptake data was available for 2016.

Influenza surveillance

The New Zealand influenza surveillance system compiles information from a variety of sources, including:

Consultation rates

The national weekly consultation rate is used to describe the overall level of influenza-like illness activity presenting to the general practice level, using the moving epidemic method to define the start of and intensity level of the influenza season.5 Figure 10.1 shows the national weekly influenza-like illness consultation rates from 2009 to 2016. In 2016 the overall influenza-like illness activity was at a low level, compared with 2015 when the influenza-like illness activity was at a moderate level, and higher than in the previous two years.

Figure 10.1: Weekly consultation rates for influenza-like illness in New Zealand, 2009–2016
Figure 10.1: Weekly consultation rates for influenza-like illness in New Zealand, 2009–2016

Source: ESR

Hospitalisations and deaths

In 2015 there were 2,012 hospitalisations (43.8 per 100,000) for influenza, the highest number since 2000 (Figure 10.2).5 Hospitalisation rates were highest in those aged under 1 year (186.1 per patient population) and aged 65 years and older (98.3 per 100,000), as well as for the Pacific (121.7 per 100,000) and Māori (49.6 per 100,000) ethnic groups. There were 263 deaths during the period 2000 to 2013: 10 were children aged under 5 years, 173 were adults aged 65 years and older and one was a pregnant woman.

The deaths that are coded directly to influenza significantly underestimate the overall burden of hospitalisation and death from the contribution of influenza. Previous modelling data suggests that for every death attributable to influenza, a further 7.7 deaths are associated with complications of influenza.6 Overseas modelling has found similar patterns of under-diagnosis, with a factor of 3.7 for the Netherlands7 and 10 for the UK.8 Modelling with New Zealand data suggests that the contribution of influenza to total hospitalisation is about nine times larger than indicated by routine discharge data.9

Figure 10.2: Hospitalisation discharge rates for influenza, 2000–2015, and mortality, 2000–2013
Figure 10.2: Hospitalisation discharge rates for influenza, 2000–2015, and mortality, 2000–2013

Source: ESR (hospitalisations) and the Ministry of Health (mortality)

As with the national rates described above, hospitalisation rates identified in the Southern Hemisphere Influenza, Vaccine Effectiveness, Research and Surveillance (SHIVERS) study running from 2012 to 2016 in Auckland and Counties Manukau DHBs were highest in the very young and elderly populations (Figure 10.3), as well as for the Pacific and Māori ethnic groups and those who reside in the most deprived NZDep2013 quintile (quintile 5).5 The influenza-associated severe acute respiratory infection hospitalisation rate for pregnant women (75.7 per 100,000) was five times higher than the rate for non-pregnant women of child-bearing age (15.2 per 100,000).

Figure 10.3: Cumulative severe acute respiratory infection-associated influenza hospitalisation incidence rate by age group, for Auckland and Counties Manukau DHBs, 2015
Figure 10.3: Cumulative severe acute respiratory infection-associated influenza hospitalisation incidence rate by age group, for Auckland and Counties Manukau DHBs, 2015

Source: ESR

Five percent of the 373 patients hospitalised with influenza-positive severe acute respiratory infection were admitted to the intensive care unit (ICU); the incidence rate was approximately five times higher among Pacific peoples compared to other ethnic groups, and concentrated among young infants.5

Asymptomatic influenza

Results from the 2015 SHIVERS influenza research serosurvey showed that around 26 percent of people in New Zealand had contracted influenza over the 2015 season.10 Approximately 80 percent of infected people (4 in 5 infected) were asymptomatic, with only 2.5 percent of those infected (1 in 40 infected) visiting their GP and 0.2 percent (1 in 560 infected) hospitalised. This data indicates that the majority of influenza infections are asymptomatic, with most symptomatic cases self-managing without seeking medical help.11

Circulating influenza strains

In 2015 a total of 5,443 viruses were typed, of which 2,999 were subtyped and lineage-typed.5 Influenza B was predominant (53.1 percent versus influenza A 46.9 percent). Among the 1,921 influenza A subtyped strains, 97.6 percent were A(H3N2) virus and 2.4 percent were A(H1N1). Among the 1,078 influenza B lineage types, 51.1 percent were Victoria and 48.9 percent Yamagata.

Influenza immunisation uptake

In 2016 more than 1.2 million doses of influenza vaccine were distributed; this is the second highest number on record, slightly less than in 2013.

The uptake rate of influenza vaccine (both publicly and privately funded), as estimated by vaccine distribution figures during the 2016 influenza immunisation programme, was 266 doses per 1,000 population, similar to the uptake in 2014 and 2015 (see Figure 10.4). Funded vaccine uptake for individuals aged 65 years and older was 66.7 percent. As this is based on immunisation claims data for publicly funded influenza vaccination, it is likely to be an underestimate.

Figure 10.4: Influenza vaccine uptake per 1,000 population, 1990–2016
Figure 10.4: Influenza vaccine uptake per 1,000 population, 1990–2016

Vaccine coverage is estimated using vaccine distribution figures.

Funded vaccine was introduced for: individuals aged 65 years and older in 1997; individuals aged under 65 years with certain medical conditions in 1999; pregnant women in 2010; children aged under 5 years with significant respiratory illness in 2013.

Source ESR and Ministry of Health

Since 2010 the Ministry of Health has requested that all DHBs provide influenza immunisation coverage data for their staff at the end of each influenza season. National influenza immunisation coverage for DHB staff is still low, but it has increased from 45 percent in 2010 to 65 percent in 2016.

10.3.3 Pandemic influenza

The natural ecology of influenza type A viruses is among wild aquatic avian species, and from time to time, these viruses spill over into other species including humans. These avian influenza virus infections are usually severe and associated with a high mortality, however, are rarely transmitted from human to human. In the past, avian viruses have become transmissible either through adaptation or the acquisition of swine or human genomic material, and when natural immunity has been lacking in the population, have resulted in a pandemic with global spread.

Pandemics have the potential to result in large numbers of severe infections, but the degree of severity is hard to predict and will depend upon many factors, including whether there is any previous community immunity. The most severe recorded pandemic was the ‘Spanish’ A(H1N1) pandemic of 1918–1920 which caused an estimated 20–50 million deaths worldwide. The most recent pandemic was the 2009 A(H1N1)pdm09 strain. It was estimated that 10 percent (800,000) of the New Zealand population were infected with the virus during the first wave, including one in every three children.12 Risk factors for severe outcomes included obesity, pregnancy,13 diabetes mellitus and Pacific or Māori ethnicity.12 This strain is now established as a circulating seasonal influenza strain.

Monitoring, surveillance and response for new pandemic strains are in place. See section 10.8.3.

10.4 Vaccines

Annual influenza vaccination is a most important measure for preventing influenza infection and mortality. The National Influenza Specialist Group coordinated by IMAC, is responsible for New Zealand’s annual Influenza Communication Campaign (www.influenza.org.nz). This campaign includes an annual influenza kit for health care professionals and a national education and communication programme.

10.4.1 Available vaccines

Funded vaccines
Other vaccines

Other influenza vaccine brands registered and available in New Zealand are:

Vaccine preparations

Influenza vaccine preparations vary by their type, the number of influenza strains contained in the vaccine and their delivery systems. There are a range of delivery mechanisms available internationally, including intradermal and intranasal mists. Intradermal vaccines are generally recognised as offering similar immune responses in healthy subjects14 and possibly more efficient immune responses,15 particularly in the older adult population.16 Live attenuated influenza vaccines are delivered by intranasal spray.

The influenza vaccine strains vary each year depending on the prevailing virus viruses. The WHO conducts technical consultations in February/March and September each year to recommend viruses for inclusion in both trivalent and quadrivalent vaccines for the northern and southern hemisphere influenza seasons, respectively. For 2017 the southern hemisphere recommendations include the two influenza type A (H1N1pdm09 and H3N2) and two B (Victoria and Yamagata) strains likely to circulate in New Zealand over the coming influenza season.

Inactivated influenza vaccines (split virion or subunit vaccines)

The trivalent inactivated vaccines (TIVs) available in New Zealand are inactivated split virion vaccines prepared from virus grown in the allantoic cavity of embryonated hens’ eggs. They contain two influenza type A strains and one type B strain. The virus is purified, disrupted and inactivated with beta-propiolactone or formaldehyde.

Quadrivalent inactivated vaccines (QIVs) contain two type A and two type B influenza strains and therefore have the potential to offer better effectiveness in seasons of B strain mismatch. One QIV (FluQuadri, Sanofi) is currently registered and available in New Zealand, and more are expected to be available, pending registration, for subsequent influenza seasons.

Live attenuated influenza vaccines (LAIVs)

LAIVs may induce stronger immune responses than TIVs, particularly in children, by mimicking natural influenza infection and evoking both mucosal and systemic immunity, and including broader cellular immune responses.17 Live attenuated influenza vaccines (LAIVs; trivalent and quadrivalent) are licensed for use in North America for healthy non‑pregnant individuals aged 2–49 years and in Europe for children aged 2–18 years.18 LAIVs have been shown to be effective in children aged 6 months to 7 years.19

However, based on recent observational data showing lack of effectiveness in US children aged 2–17 years for the 2013/14 and 2015/16 influenza seasons, the US Advisory Committee on Immunization Practices (ACIP) has recommended that LAIVs not be used for the 2016/17 influenza season.18

In contrast, UK data from the 2015/2016 season has shown a LAIV effectiveness in children aged 2–17 years of 57.6 percent (95% CI: 25.1–76.0) against any influenza, with higher vaccine effectiveness (81.4 percent; 95% CI: 39.6–94.3) against the B strain.20 It is not currently clear why there are such significant effectiveness differences for different regions, although variations in circulating strain matches, the make-up of the LAIV itself and previous vaccination history may all have some effect.20

At the time of writing, LAIVs were not registered in New Zealand.

Adjuvanted vaccines

Adjuvants enhance the immune response to an antigen. There are three adjuvants licensed (internationally) for use in influenza vaccines: two oil-in-water emulsions, and a third that uses immunopotentiating reconstituted influenza virosomes.21

Vaccines with these adjuvants show modestly improved immune responses, which may be particularly useful for the elderly, but may also cause more local and systemic reactions than unadjuvanted vaccines.21 At the time of writing, influenza vaccines containing these adjuvants were not registered and/or available in New Zealand.

10.4.2 Efficacy and effectiveness

International data

The efficacy (prevention of illness among vaccinated individuals in controlled trials) and effectiveness (prevention of illness in vaccinated populations) of influenza vaccine depends on several factors. The age and immune competence of the vaccine recipient are important, as well as the match between the virus strains in the vaccine and those in circulation each year. Previous vaccination history may reduce the vaccine effectiveness in some cases, possibly more so when the previous vaccination was mismatched with the circulating strains at the time.22

The current data for vaccine efficacy and effectiveness of TIVs is summarised in Table 10.1.

Table 10.1: Current estimates of TIV influenza vaccine efficacy and effectiveness
Population Type of outcome Level of protection (95% confidence intervals)
Infants aged under 6 months whose mothers received influenza vaccine Efficacy against laboratory-confirmed influenza 41–48%23, 24
Healthy children aged under 2 years Efficacy against laboratory-confirmed influenza Insufficient data19, 25
Effectiveness against laboratory-confirmed influenza 66% (9–88)26
Healthy children aged 6–35 months Effectiveness against laboratory-confirmed influenza 66% (29–84)26
Healthy children aged under 16 years TIV vaccine efficacy in prevention of laboratory-confirmed influenza in randomised controlled trials 59% (41–71)25
Healthy adults aged 18–65 years Effectiveness against influenza-like illness* 30% (17–41)27
Efficacy against influenza symptoms* 73% (54–84)27
Efficacy against laboratory-confirmed influenza 59% (51–67)19
Those aged 65 years and older Effectiveness in preventing influenza, influenza-like-illness, hospitalisations, complications and mortality Inconclusive due to poor quality of studies28
Those aged 65 years and older Effectiveness against non-fatal and fatal complications 28% (26–30)29
Effectiveness against influenza-like illness 39% (35–43)29
Effectiveness against laboratory-confirmed influenza 49% (33–62)29

*     From age 16 years.

Vaccine effectiveness in New Zealand

New Zealand data is consistent with international data. While there is some variability from year to year and with different strains, overall the data shows that TIV influenza vaccine effectiveness is approximately 50 percent overall for preventing both visits to the general practice and hospitalisations, for both influenza type A and B strains.30, 31, 32, 33 However, estimates for vaccine effectiveness tend to be higher in children and healthy midlife adults, and lower in the elderly.

Pregnant women and neonates

A pregnant woman and her fetus are at increased risk of influenza complications, including hospitalisation from influenza-related cardiorespiratory disorders during the second and third trimesters, and this was especially apparent in the 2009 pandemic.34 Influenza immunisation is therefore recommended during pregnancy to reduce this risk. Influenza immunisation is expected to have the same efficacy in healthy pregnant women as in other healthy adults.

Maternal influenza immunisation also offers protection to the fetus through maternal antibody transfer.17, 24, 34, 35 Influenza vaccines are not registered and have not been shown to be effective in infants aged under 6 months, therefore immunisation during pregnancy confers protection to newborns and infants who are too young to have received vaccination at the time of exposure.23, 36 Maternal influenza immunisation is significantly associated with reduced risk of influenza virus infection and hospitalisation for an influenza-like illness in infants up to 6 months of age, and increased influenza antibody titres are seen in infants through to age 2–3 months.23

Influenza immunisation during pregnancy may also reduce the incidence of stillbirth. In an Australian study, stillbirth was 51 percent less likely among vaccinated mothers compared to unvaccinated mothers.37

Children

The evidence for vaccine efficacy and effectiveness in very young children is varied. There is evidence to support moderate effectiveness of TIV in children aged 3 years and older.

Healthy adults

Generally, randomised placebo-controlled trials of TIV in healthy adults support good protection against a variety of outcomes, particularly laboratory-confirmed influenza.

Adults aged over 65 years

Although less effective at preventing clinical illness in older people,38 influenza vaccination does reduce hospitalisation and deaths. A 1995 meta-analysis of 20 cohort studies in older people estimated that influenza vaccine prevented 56 percent of upper respiratory illnesses, 53 percent of pneumonias, 50 percent of all hospitalisations and 68 percent of deaths.39

There is wide variability in the estimates of effectiveness of annual influenza vaccination against influenza-like illness in nursing home residents (0–80 percent).21 Vaccination has been demonstrated to prevent hospitalisation and death in these groups,39, 40, 41, 42 but a 2010 Cochrane review concluded that there was insufficient evidence to support influenza vaccine effectiveness in the elderly.28 However, researchers have more recently re-examined this review and its methodology and argue that there is substantial evidence for the ability of influenza vaccine to reduce the risk of influenza infection and influenza-related disease and death in the elderly.29

Adults with co-morbid conditions

Influenza vaccination has been associated with reductions in hospitalisations and deaths among adults with risk factors for influenza complications. Among Danish adults aged under 65 years with underlying medical conditions, vaccination reduced all-cause deaths by 78 percent and hospitalisations attributable to respiratory infections or cardiopulmonary diseases by 87 percent.43 Benefits from influenza vaccination have been observed for both diabetes44 and chronic obstructive pulmonary disease.45 An Australian study of adults aged 40 years and older showed that unvaccinated adults are almost twice as likely as vaccinated adults to have an acute myocardial infarct.46

Herd immunity

There is some evidence to suggest that herd immunity can be achieved, particularly by vaccinating children.47 Some studies suggest that herd immunity may also be achieved in nursing homes if immunisation coverage of residents is greater than 80 percent.48 Vaccinating health care workers is likely to be an effective strategy, particularly when in contact with high-risk patients such as in nursing homes.49

The UK has had three seasons of a progressively rolled-out vaccination programme using LAIV, starting with children aged 2–3 years in 2013/14 and then extended to children aged 4–7 years by 2015/16. There were also school-age pilot programmes in England for older children. Early results show evidence of indirect and overall impact, with decreases in disease incidence and influenza positivity in the school-age pilots versus control areas in vaccinated and non-vaccinated groups.50

Duration of immunity

Due to the continual drift of influenza viruses, duration of immunity provided by influenza vaccines is difficult to study. However, when the strains stay the same for consecutive years, vaccination in a previous year appears to confer immunity into the next year for healthy adults and children.18, 21 However shorter duration of immunity is likely in other groups, particularly the elderly.18

Protection due to LAIVs has been demonstrated to persist beyond a year.51, 52

10.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.53 Store at +2°C to +8°C. Do not freeze. Influvac should be stored in the dark.

10.4.4 Dosage and administration

The funded trivalent influenza vaccine should be administered by intramuscular or subcutaneous injection (see section 2.2.3). The contents of the syringe must be shaken thoroughly before use.

Individuals aged 9 years and older

Individuals aged 9 years and older receive a single 0.5 mL intramuscular dose of vaccine.

Children aged under 9 years

Children aged under 9 years who have not previously received influenza vaccine require two doses of vaccine four weeks apart to produce a satisfactory immune response. Children aged 6–35 months are given a 0.25 mL dose (see Table 10.2 and the manufacturer’s data sheet for the dose in children).

Table 10.2: Recommended influenza vaccine doses in children
Age Dose Number of doses
6–35 months 0.25 mL 1 or 2*
3–8 years 0.5 mL 1 or 2*

*     Two doses separated by at least four weeks if the vaccine is being used for the first time.

There is limited data on which to base the recommendations, but the aim is to reduce reactions, particularly febrile reactions (which are increased in young children), while maintaining an adequate immune response.

Immunocompromised individuals

Regardless of their age, previously unvaccinated immunocompromised individuals are recommended to receive two doses of influenza vaccine, four weeks apart.54 One dose is then given in each subsequent year. (See section 4.3.)

Co-administration with other vaccines

Influenza vaccine can be administered with other vaccines, such as pneumococcal polysaccharide vaccine and the scheduled childhood vaccines. Individuals recommended to receive both influenza vaccine and 13-valent pneumococcal conjugate vaccine (PCV13) have an increased risk of fever following concurrent administration of these vaccines.55, 56 Separation of the vaccines by two days can be offered, but is not essential. (See also section 15.6.2.)

10.5 Recommended immunisation schedule

The optimal time to vaccinate people in high-risk groups is usually during March and April. This is in advance of the usual May to September period of influenza virus activity. The vaccine can be given even when influenza virus activity has been identified, because protective antibody levels develop from four days after immunisation, with full protection after two weeks.57 The vaccine should be administered annually to maintain immunity and to provide protection against new strains.

Vaccine effectiveness may be reduced in those at highest risk from influenza. Therefore, it is important to consider not just individual protection but also reducing spread by vaccinating contacts of high-risk individuals, such as family and caregivers, and occupational vaccination. See Table 10.3 for a summary of the funded and unfunded recommendations for influenza immunisation.

Table 10.3: Influenza vaccine recommendations

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to the funding decisions.

Recommended and funded
All individuals aged 65 years and older.

Individuals aged 6 months to under 65 years who:

  • have cardiovascular disease (ischaemic heart disease, congestive heart failure, rheumatic heart disease, congenital heart disease or cerebrovascular disease)
  • have chronic respiratory disease (asthma if on regular preventive therapy; other chronic respiratory disease with impaired lung function)
  • have diabetes
  • have chronic renal disease
  • have any cancer, excluding basal and squamous skin cancers if not invasive
  • have other conditions (autoimmune disease, immunosuppression or immune deficiency, HIV infection, transplant recipients, neuromuscular and central nervous system diseases/disorders, haemoglobinopathies, children on long-term aspirin, have a cochlear implant, errors of metabolism at risk of major metabolic decompensation, pre- or post-splenectomy, Down syndrome)
  • are pregnant
  • are children aged 4 years and under who have been hospitalised for respiratory illness or have a history of significant respiratory illness
  • are patients who are compulsorily detained long-term in a forensic unit within a DHB hospital.*
Recommended but not funded
Individuals with asthma not requiring regular preventive therapy
Individuals with functional asplenia
Individuals in essential positions and health care workers
Individuals who may transmit influenza to persons at increased risk of complications from influenza infection
Travellers
Children aged under 5 years
Residents of residential care facilities
The homeless

*     This is a Pharmaceutical Schedule Section H – Hospital Medicines List funding restriction.

10.5.1 Pregnancy and breastfeeding

The influenza vaccine is strongly recommended, and funded, for women who will be pregnant while the vaccine is available.

Influenza vaccine is safe to administer during any stage of pregnancy or while breastfeeding. There is no evidence that influenza vaccine prepared from inactivated virus causes damage to the fetus or neonate58 and some evidence it may be protective against stillbirth.37

Pregnant women are at greater risk from complications associated with influenza illness. When pregnancy is superimposed on high-risk conditions such as asthma or diabetes, influenza-related morbidity is three to four times greater than in non-pregnant women with similar high-risk conditions.

Because there is no registered or effective vaccine for children aged under 6 months, vaccination during pregnancy is highly recommended to improve maternal fetal passive antibody transfer.36 Influenza vaccination of pregnant women has been shown to significantly decrease influenza in their newborn babies.17, 24, 34, 35 Breastfeeding is also recommended, to deliver passive immunity to the infant.17 (See also section 4.1.2.)

10.5.2 At-risk children

Influenza vaccine is funded for children aged 6 months and older with chronic illnesses and a history of respiratory disease. Children with the following conditions should be prioritised to receive influenza vaccine due to their increased risk:

Special considerations apply to children, as follows.

10.5.3 At-risk adults

Adults aged 65 years and older

In adults aged 65 years and older, influenza vaccine has been shown to be effective against non-fatal and fatal influenza complications, influenza-like illness and laboratory-confirmed influenza (see Table 10.1).

Adults with underlying medical conditions

Influenza has been associated with increased morbidity and mortality in adults with underlying medical conditions.

10.5.4 Recommended but not funded

Influenza vaccine is recommended, but not funded, for the groups listed in Table 10.3.

Healthy adults

Healthy individuals are encouraged to have the vaccine, especially if they are in close contact with individuals at high risk of complications. Employers are encouraged to provide influenza vaccine to avoid illness in their employees, especially those engaged in health care and other essential community services. Immunising healthy individuals has been shown to be cost-effective.

In order to optimise the protection of high-risk (see Table 10.3) infants and toddlers (including those aged under 6 months) all household and close contacts should receive influenza vaccine (not funded unless eligibility criteria are met).

Health care workers

The Ministry of Health strongly recommends, and expects, that all health care workers will receive annual influenza vaccination for their own protection and the protection of those in their care.

Travellers

People travelling outside New Zealand, especially those who are in the at-risk groups who have not received vaccine during the previous autumn, are recommended to have influenza vaccination depending on the season and their destination. In tropical countries, influenza activity can occur throughout the year but is more likely during the winter (wet) and summer seasons, while in the northern hemisphere activity is commonest between the months of December and March. Outbreaks of influenza among organised tourist groups (eg, on cruise ships) can occur throughout the year.

10.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

10.6.1 Contraindications

Influenza vaccine should not be administered to people with a history of an anaphylactic reaction to a prior dose of influenza vaccine or to a vaccine component. Known egg allergy is a precaution, see section 10.6.2.

Fluvax is contraindicated for children aged under 5 years (see section 10.7) due to the increased risk of febrile events. The Ministry of Health recommends that Fluvax not be given to children aged under 9 years.

10.6.2 Precautions

Known egg allergy

Non-anaphylactic egg allergy is not a contraindication to influenza vaccination. A history of anaphylaxis to egg has been considered a contraindication to influenza vaccination. However, there is developing evidence that it may be given safely.59, 60 Reported cases of anaphylaxis after influenza vaccination in egg-allergic individuals all occurred over 20 years ago, at a time when vaccine egg (ovalbumin) content was much higher than it is now.

Persons with a history of egg allergy who have experienced non-severe allergic reactions such as hives after exposure to egg should receive influenza vaccine. Those who have reactions to egg involving symptoms that may have an anaphylactic element to them such as angioedema, respiratory distress, or had previous use of adrenaline for a reaction may receive a vaccination but it is recommended that the first dose be delivered within a closely monitored environment such as a hospital or outpatient clinic.18

History of Guillain–Barré syndrome

There appears to be a small increase in the risk of GBS following influenza vaccination (less than one additional case per million doses administered,18 substantially less than the risk of developing severe complications from influenza infection21, 27). There is also an increased risk of developing GBS following influenza infection, and the magnitude of the risk is several times greater than that following influenza vaccination.61

New Zealand hospitalisations for GBS showed no increase during the 1990s despite the marked increase in vaccine use during this period, but did show a marked year-to-year variation. In particular, the doubling of vaccine use in 1997 (with the introduction of funded vaccine) was not associated with any increase in GBS hospitalisations. No excess risk for GBS following influenza vaccine in children has been documented. No association between influenza vaccines and any other neurological disease has been substantiated.

The risks and benefits of withholding vaccination should be considered on an individual basis, based on the potential morbidity and mortality associated with influenza for that individual, including the potential risk of recurrent GBS following influenza infection.

Co-administration with PCV13

Individuals (or their parents/guardians) who are recommended to receive both influenza vaccine and 13-valent pneumococcal conjugate vaccine (PCV13) should be advised of the increased risk of fever following concomitant administration of these vaccines.55, 56 Separation of the vaccines by two days can be offered, but is not essential. (See also section 15.6.2.)

10.7 Expected responses and AEFIs

TIV influenza vaccines are generally well tolerated. Placebo-controlled trials of TIVs have shown that influenza vaccine is not associated with systemic reactions (eg, fever, malaise, myalgia) in older persons and healthy young adults.18 Systemic reactions are more likely in children not previously exposed to the vaccine or virus, these are generally self-limiting and resolve within one to two days.18 A large post-licensure study in the US, which reviewed more than 250,000 children aged under 18 years given influenza vaccine, showed no increase in clinically important medically attended events for two weeks after vaccination compared to control periods.62

In early 2010 there were reports of children in both Australia and New Zealand who had received the influenza vaccine and experienced febrile seizures. All of the cases were linked to the Fluvax brand of vaccine.

Vaccinators need to emphasise to recipients that:

Local reactions, including redness and induration at the injection site, may persist for one to two days in 10–64 percent of adult recipients, but these effects are usually mild.18 Passive reporting of local and systemic reactions to influenza vaccines is more frequent for females (both young and older adults) than males.63

The safety profile of quadrivalent inactivated vaccines is comparable to that of trivalent inactivated vaccines.18

In 2010 an association was found between one H1N1 pandemic vaccine (an adjuvanted vaccine not licensed or used in New Zealand) and narcolepsy. There is now data from a number of European countries that supports a temporal link.64, 65, 66 The association may have been related to the adjuvant. However, it is possible that the onset of narcolepsy may be confounded by other factors (such as genetic predisposition, (H1N1)pdm09 influenza and/or other environmental factors).65, 67, 68 Further data is required to confirm the strength of this association and the size of the risk, and to identify the underlying biological mechanisms.65, 69

See section 10.6.2 for information on egg allergy.

10.8 Public health measures

Using influenza signs and symptoms to assess the burden of influenza is of limited value. There is also a significant amount of asymptomatic circulation of influenza in the community. The most sensitive diagnostic method is polymerase chain reaction (PCR) of respiratory nasopharyngeal swabs or aspirate samples.

The methods of controlling influenza are:

10.8.1 Improving vaccine uptake

Studies in New Zealand and overseas have found that provider attitudes and recommendations are key to improving influenza vaccine uptake. Organised registers for recall and opportunistic immunisation are also likely to be important factors in achieving high uptake.

Every effort should be made during March and April to immunise all people at risk, such as those aged 65 years and older, those aged under 65 years (including children) who have certain medical conditions, pregnant women and health care workers. A decision to offer immunisation in winter, during an influenza epidemic, to those who were not immunised in the autumn will depend on the circumstances of the outbreak or epidemic, among other factors. Availability of an appropriate vaccine is the most pertinent of these factors. Vaccination of healthy adults and children is encouraged but is not funded by the Ministry of Health; adult vaccination may be funded by employers.

10.8.2 Antiviral drugs

Influenza antiviral drugs can be used to treat or to prevent influenza and can be adjuncts to influenza vaccination. Use of antivirals very early in an illness can reduce the duration of symptoms and the risk of complications from influenza. Clinical benefit is greatest if antivirals are used as early as possible, especially within the first 48 hours of the illness.

Meta-analyses of the effectiveness of oseltamivir in treating uncomplicated influenza show a reduction in duration of symptoms for healthy adults and adolescents of around one day,70 a 63 percent (95% CI: 19–83) decreased risk of hospitalisation for any cause and a 44 percent (95% CI: 25–58) decreased risk of antibiotic prescription use.71 For use with severe influenza, observational studies show early treatment is critical, and can lead to a decreased risk for death.72, 73

Antivirals should be considered for unimmunised or recently immunised contacts who are at high risk of severe disease. When used to limit the size of an institutional outbreak, antiviral drugs are usually given for a period of two weeks after immunisation or until one week after the end of the outbreak. Institutional outbreaks should be notified to the local medical officer of health.74

10.8.3 Pandemics

At the time of a pandemic, the public health advice, priority groups and the timing of vaccination may be quite different from those during inter-pandemic periods. The New Zealand Influenza Pandemic Plan: A framework for action75 describes the key phases of a pandemic and the actions and responsibilities within each phase.

10.9 Variations from the vaccine data sheet

The data sheet states that for pregnant high-risk patients, the possible risks of clinical influenza infection should be weighed against the possible risks of vaccination. The Ministry of Health recommends that all pregnant women receive influenza vaccination – see section 10.5.1.

The data sheet states that hypersensitivity to eggs is a contraindication to receiving influenza vaccination. The Ministry of Health recommends that individuals with hypersensitivity to eggs may receive influenza vaccination – but those with an anaphylactic component should be vaccinated in a closely monitored environment such as a hospital or outpatient clinic18 – see section 10.6.2.

References

  1. Fine PEM, Mulholland K. 2013. Community immunity. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  2. Lowen AC, Mubareka S, Steel J, et al. 2007. Influenza virus transmission is dependent on relative humidity and temperature. PLOS Pathogens 3(10): e151. DOI: 10.1371/journal.ppat.0030151 (accessed 29 October 2013).
  3. World Health Organization. 2014. Influenza (Seasonal). URL: http://www.who.int/mediacentre/factsheets/fs211/en/ (accessed 17 November 2016).
  4. World Health Organization. 2010. Pandemic (H1N1) 2009 – Update 112 (6 August 2010). URL: http://www.who.int/csr/don/2010_08_06/en/ (accessed 28 November 2016).
  5. Institute of Environmental Science and Research Ltd. 2016. Influenza Surveillance in New Zealand 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/Virology/FluAnnRpt/InfluenzaAnn2015.pdf (accessed 17 November 2016).
  6. Public Health Commission. 1996. Influenza: The Public Health Commission’s advice to the Minister of Health 1995–1996. URL: http://www.moh.govt.nz/notebook/nbbooks.nsf/0/EC407ECFED0EAF624C2565D7001877CA/$file/influenza.pdf (accessed 29 October 2013).
  7. Sprenger MJW, Mulder PGH, Beyer WEP, et al. 1993. Impact of influenza on mortality in relation to age and underlying disease, 1967–1989. International Journal of Epidemiology 22(2): 334–40.
  8. Ashley J, Smith T, Dunnell K. 1991. Deaths in Great Britain associated with the influenza epidemic of 1989/90. Population Trends 65: 16–20.
  9. Khieu T, Pierse N, Telfar-Barnard LF, et al. 2015. Estimating the contribution of influenza to hospitalisations in New Zealand from 1994 to 2008. Vaccine 33(33): 4087–92.
  10. Huang S (on behalf of the SHIVERS Investigation team). 2016. Key Findings – SHIVERS. Presented at the 2016 New Zealand Influenza Symposium (updated January 2017). URL: http://www.immune.org.nz/sites/default/files/conferences/2016/NZiS2016/8%201310%2020161102%20NZiS%20SHIVERSRevisedJan2017.pdf (accessed 20 February 2017).
  11. Hayward AC, Fragaszy EB, Bermingham A, et al. 2014. Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study. The Lancet Respiratory Medicine 2(6): 445–54. URL: http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970034-7/fulltext (accessed 21 November 2016).
  12. Institute of Environmental Science and Research Ltd. 2009. Seroprevalence of the 2009 Influenza A (H1N1) Pandemic in New Zealand. URL: www.health.govt.nz/publication/seroprevalence-2009-influenza-h1n1-pandemic-new-zealand (accessed 29 October 2013).
  13. Siston AM, Rasmussen SA, Honein MA, et al. 2010. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. Journal of the American Medical Association 303(15): 1517–25.
  14. Patel SM, Atmar RL, El Sahly HM, et al. 2012. Direct comparison of an inactivated subvirion influenza A virus subtype H5N1 vaccine administered by the intradermal and intramuscular routes. Journal of Infectious Diseases 206(7): 1069–77.
  15. Roukens AHE, Gelinck LBS, Visser LG. 2012. Intradermal vaccination to protect against yellow fever and influenza. Current Topics in Microbiology and Immunology 351: 159–79. DOI: 10.1007/82_2011_124 (accessed 12 November 2012).
  16. Marra F, Young F, Richardson K, et al. 2012. A meta-analysis of intradermal versus intramuscular influenza vaccines: immunogenicity and adverse events. Influenza and Other Respiratory Viruses 7(4): 584–603. DOI: 10.1111/irv.12000 (accessed 15 December 2012).
  17. Esposito S, Tagliabue C, Tagliaferri L, et al. 2012. Preventing influenza in younger children. Clinical Microbiology and Infection 18(Suppl 5): 42–9.
  18. Centers for Disease Control and Prevention. 2016. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2016–17 influenza season. Morbidity and Mortality Weekly Report: Recommendations and Reports 65(RR05): URL: https://www.cdc.gov/mmwr/volumes/65/rr/rr6505a1.htm (accessed 12 September 2016).
  19. Osterholm MT, Kelley NS, Sommer A, et al. 2012. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet Infectious Diseases 12(1): 36–44.
  20. Pebody R, Warburton F, Ellis J, et al. 2016. Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results. Euro Surveillance 31(38): pii=30348. URL: http://www.eurosurveillance.org/images/dynamic/EE/V21N38/art22592.pdf (accessed 7 November 2016).
  21. Fiore AE, Bridges CB, Katz JM, et al. 2013. Inactivated influenza vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  22. Skowronski DM, Chambers C, Sabaiduc S, et al. 2016. A perfect storm: impact of genomic variation and serial vaccination on low influenza vaccine effectiveness during the 2014–2015 season. Clinical Infectious Diseases 63(1): 23–32. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901864/ (accessed 7 November 2016).
  23. Eick AA, Uyeki TM, Klimov A, et al. 2011. Maternal influenza vaccination and effect on influenza virus infection in young infants. Archives of Pediatrics and Adolescent Medicine 165(2): 104–11.
  24. Poehling KA, Szilagyi PG, Staat MA, et al. 2011. Impact of maternal immunization on influenza hospitalizations in infants. American Journal of Obstetrics and Gynecology 204(6 Suppl 1): S141–8.
  25. Jefferson T, Rivetti A, Di Pietrantonj C, et al. Vaccines for preventing influenza in healthy children. Cochrane Database of Systematic Reviews 2012, Issue 8, Art. No. CD004879. DOI: 10.1002/14651858.CD004879.pub4 (accessed 13 November 2012).
  26. Heinonen S, Silvennoinen H, Lehtinen P, et al. 2011. Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: An observational cohort study. The Lancet Infectious Diseases 11(1): 23–9.
  27. Jefferson T, Di Pietrantonj C, Rivetti A, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2010, Issue 7, Art. No. CD001269. DOI: 10.1002/14651858.CD001269.pub4 (accessed 13 November 2012).
  28. Jefferson T, Di Pietrantonj C, Al-Ansary LA, et al. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010, Issue 2, Art. No. CD004876. DOI: 10.1002/14651858.CD004876.pub3 (accessed 13 November 2012).
  29. Beyer WEP, McElhaney J, Smith DJ, et al. 2013. Cochrane re-arranged: support for policies to vaccinate elderly people against influenza. Vaccine 31(50): URL: http://dx.doi.org/10.1016/j.vaccine.2013.09.063 (accessed 11 November 2013).
  30. Turner N, Pierse N, Bissielo A, et al (on behalf of the SHIVERS Investigation team). 2014. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012. Vaccine 32(29):
    3687–93.
  31. Turner N, Pierse N, Bissielo A, et al (on behalf of the SHIVERS Investigation team). 2014. Effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2013. Euro Surveillance 19(34): pii=20884. URL: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20884 (accessed 3 November 2016).
  32. Pierse N, Kelly H, Thompson MG, et al (on behalf of the SHIVERS Investigation team). 2016. Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014. Vaccine 34(4): 503–9. URL: http://dx.doi.org/10.1016/j.vaccine.2015.11.073 (accessed 3 November 2016).
  33. Bissielo A, Pierse N, Huang S, et al (on behalf of the SHIVERS Investigation team). 2016. Effectiveness of seasonal influenza vaccine in preventing influenza primary care visits and hospitalisation in Auckland, New Zealand in 2015: interim estimates. Euro Surveillance 21(1): pii=30101. URL: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21342 (accessed 3 November 2016).
  34. Tamma PD, Ault KA, del Rio C, et al. 2009. Safety of influenza vaccination during pregnancy. American Journal of Obstetrics and Gynecology 201(6): 547–52.
  35. Zaman K, Roy E, Arifeen SE, et al. 2008. Effectiveness of maternal influenza immunization in mothers and infants. New England Journal of Medicine 359(15): 1555–64.
  36. Marshall H, McMillan M, Andrews RM et al. 2016. Vaccines in pregnancy: the dual benefit for pregnant women and infants. Human Vaccines & Immunotherapeutics 12(4): 848–56. DOI: 10.1080/21645515.2015.1127485 (accessed 24 September 2016).
  37. Regan A, Moore HC, de Klerk N, et al. 2016. Seasonal trivalent influenza vaccination during pregnancy and the incidence of stillbirth: population-based retrospective cohort study. Clinical Infectious Diseases 62(10): 1221–7. DOI: 10.1093/cid/ciw082 (accessed 17 November 2016).
  38. Govaert TME, Thijs C, Masurel N, et al. 1994. The efficacy of influenza vaccination in elderly individuals: a randomized double blind placebo controlled trial. Journal of the American Medical Association 272(21): 1661–5.
  39. Gross PA, Hermogenes AW, Sacks HS, et al. 1995. The efficacy of influenza vaccine in elderly persons: A meta-analysis and review of the literature. The Annals of Internal Medicine 123(7): 518–27.
  40. Deguchi Y, Takasugi Y, Tatara K. 2000. Efficacy of influenza vaccine in the elderly in welfare nursing homes: Reduction in risks of mortality and morbidity during an influenza A (H3N2) epidemic. Journal of Medical Microbiology 49(6): 553–6.
  41. Gross PA, Quinnan GV, Rodstein M, et al. 1988. Association of influenza immunization with reduction in mortality in an elderly population: a prospective study. Archives of Internal Medicine 148(3): 562–5.
  42. Saah AJ, Neufeld R, Rodstein M, et al. 1986. Influenza vaccine and pneumonia mortality in a nursing home population. Archives of Internal Medicine 146(1): 2353–7.
  43. Hak E, Buskens E, van Essen GA, et al. 2005. Clinical effectiveness of influenza vaccination in persons younger than 65 years with high-risk medical conditions: the PRISMA study. Archives of Internal Medicine 165(3): 274–80.
  44. Looijmans-Van den Akker I, Verheij TJ, Buskens E, et al. 2006. Clinical effectiveness of first and repeat influenza vaccination in adult and elderly diabetic patients. Diabetes Care 29(8): 1771–6.
  45. Poole PJ, Chacko E, Wood-Baker RW, et al. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 1, Art. No. CD002733. DOI: 10.1002/14651858.CD002733.pub2 (accessed 29 October 2013).
  46. MacIntyre R, Heywood A, Kovoor P, et al. 2013. Ischaemic heart disease, influenza and influenza vaccination: a prospective case control study. Heart 99(24): 1843–8. DOI: 10.1136/heartjnl-2013-304320 (accessed 13 November 2013).
  47. Mertz D, Fadel SA, Lam P, et al. 2016. Herd effect from influenza vaccination in non-healthcare settings: a systematic review of randomised controlled trials and observational studies. Euro Surveillance 21(42): pii=30378. URL: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.42.30378 (accessed 28 November 2016).
  48. Oshitani H, Saito R, Seki N, et al. 2000. Influenza vaccination levels and influenza‐like illness in long‐term care facilities for elderly people in Niigata, Japan, during an influenza A (H3N2) epidemic. Infection Control and Hospital Epidemiology 21(11): 728–30.
  49. Hayward AC, Harling R, Wetten S, et al. 2006. Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial. British Medical Journal 33(7581): 1241.
  50. Pebody R. 2016. UK Paediatric Influenza Vaccine Programme. Presented at the 2016 New Zealand Influenza Symposium. URL: www.immune.org.nz/sites/default/files/conferences/2016/NZiS2016/Child%20flu%20programme%20Pebody%20%20New%20Zealand.pdf (accessed 28 November 2016).
  51. Gaglani MJ, Piedra PA, Herschler GB, et al. 2004. Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000–2001 influenza A(H1N1) and B epidemic in healthy children. Archives of Pediatric and Adolescent Medicine 158(1): 65–73.
  52. Ambrose CS, Yi T, Walker RE, et al. 2008. Duration of protection provided by live attenuated influenza vaccine in children. Pediatric Infectious Disease Journal 27(8): 744–8. DOI: 10.1097/INF.0b013e318174e0f8 (accessed 4 November 2013).
  53. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  54. Department of Health and Ageing. 2016. Vaccination for special risk groups. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part3 (accessed 1 September 2016).
  55. Tse A, Tseng HF, Greene SK, et al. 2012. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project,
    2010–2011. Vaccine 30(11): 2024–31.
  56. Van Buynder PG, Frosst G, Van Buynder JL, et al. 2012. Increased reactions to pediatric influenza vaccination following concomitant pneumococcal vaccination. Influenza and Other Respiratory Viruses 7(2): 184–90. DOI: 10.1111/j.1750-2659.2012.00364.x (accessed 15 November 2012).
  57. Zuckerman M, Cox R, Taylor J, et al. 1993. Rapid immune response to influenza vaccine. The Lancet 342(8879): 1113.
  58. Bednarczyk RA, Adjaye‐Gbewonyo D, Omer SB. 2012. Safety of influenza immunization during pregnancy for the fetus and the neonate. American Journal of Obstetrics and Gynecology 207(3 Suppl): 38–46.
  59. Shimizu M, Imai T, Yamazaki S, et al. 2016. Safety of influenza vaccination in children with severe allergy to hens’ eggs: a prospective case series study. Arerugi (Allergy) 65(2): 128–33.
  60. Erlewyn-Lajeunesse M, Brathwaite N, Lucas JSA, et al. 2009. Recommendations for the administration of influenza vaccine in children allergic to egg. British Medical Journal 339(1136): 3680.
  61. Vellozzi C, Iqbal S, Broder K. 2016. Guillain-Barré syndrome, influenza, and influenza vaccination: the epidemiologic evidence. Clinical Infectious Diseases 58(8): 1149–55. DOI: 10.1093/cid/ciu005 (accessed 14 February 2017).
  62. France EK, Glanz JM, Xu S, et al. 2004. Safety of the trivalent inactivated influenza vaccine among children: a population-based study. Archives of Pediatric & Adolescent Medicine 158(11): 1031–6. DOI: 10.1001/archpedi.158.11.1031 (accessed 3 November 2016).
  63. Klein SL, Marriott I, Fish EN. 2015. Sex-based differences in immune function and responses to vaccination. Transactions of the Royal Society of Tropical Medicine and Hygiene 109(1): 9–15. DOI: 10.1093/trstmh/tru167 (accessed 3 November 2016).
  64. National Institute for Health and Welfare (THL). 2011. Reported incidence of narcolepsy in children and adolescents after Pandremix/Arepanrix vaccination. URL: https://www.thl.fi/documents/10531/104009/Narkolepsia_posteri.pdf (accessed 14 February 2017).
  65. European Centre for Disease Prevention and Control. 2012. Narcolepsy in association with pandemic influenza vaccination (a multi-country European epidemiological investigation). URL: http://ecdc.europa.eu/en/publications/Publications/Vaesco%20report%20FINAL%20with%20cover.pdf (accessed 14 February 2017).
  66. World Health Organization. 2011. Statement on Narcolepsy and Vaccination. URL: http://www.who.int/vaccine_safety/committee/topics/influenza/pandemic/h1n1_safety_assessing/narcolepsy_statement/en/ (accessed 15 December 2012).
  67. Dauvilliers Y, Montplaisir J, Cochen V, et al. 2010. Post-H1N1 narcolepsy-cataplexy. Sleep 33(11): 1428–30.
  68. Han F, Lin L, Warby SC, et al. 2011. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Annals of Neurology 70(3): 410–7.
  69. World Health Organization. 2013. Global Advisory Committee on Vaccine Safety, 12–13 June 2013. Weekly Epidemiological Record 88(29): 301–12. URL: www.who.int/vaccine_safety/committee/reports/wer8829.pdf (accessed 4 November 2013).
  70. Jefferson T, Jones M, Doshi P, et al. 2014. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. British Medical Journal 348(9 April): g2545. DOI: 10.1136/bmj.g2545 (accessed 28 November 2016).
  71. Dobson J, Whitley RJ, Pocock S, et al. 2015. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. The Lancet 385(9979): 1729–37. URL: http://dx.doi.org/10.1016/S0140-6736(14)62449-1 (accessed 28 November 2016).
  72. Muthuri SG, Venkatesan S, Myles PR, et al. 2014. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. The Lancet Respiratory Medicine 2(5):
    395–404.
  73. Hiba V, Chowers M, Levi-Vinograd I, et al. 2011. Benefit of early treatment with oseltamivir in hospitalized patients with documented 2009 influenza A (H1N1): retrospective cohort study. Journal of Antimicrobial Chemotherapy 66(5): 1150–5.
  74. Ministry of Health. 2017. Guidance on Infectious Disease Management under the Health Act 1956. URL: http://www.health.govt.nz/publication/guidance-infectious-disease-management-under-health-act-1956 (accessed 20 February 2017).
  75. Ministry of Health. 2010. New Zealand Influenza Pandemic Plan: A framework for action. URL: www.health.govt.nz/publication/new-zealand-influenza-pandemic-plan-framework-action (accessed 29 August 2013).

11 Measles

In this chapter:

Key information

11.1 Virology

11.2 Clinical features

11.3 Epidemiology

11.4 Vaccines

11.5 Recommended immunisation schedule

11.6 Contraindications and precautions

11.7 Expected responses and AEFIs

11.8 Public health measures

11.9 Variations from the vaccine data sheet

References

Key information

Mode of transmission By direct contact with infectious droplets or by airborne spread. Measles is one of the most highly communicable of all infectious diseases.
Incubation period About 10 days, but may be 7–18 days from exposure to onset of fever. The incubation period may be longer in those given IG after exposure.
Period of communicability From 5 days before to 5 days after rash onset, counting the day of rash onset as day 1.
Herd immunity threshold To prevent recurrent outbreaks of measles, 95 percent of the population must be immune.
Funded vaccine MMR vaccine (Priorix) is a live attenuated vaccine.
Dose, presentation, route

0.5 mL per dose after reconstitution.

Pre-filled syringe and glass vial. The vaccine must be reconstituted prior to injection.

Subcutaneous injection.

Funded vaccine indications and schedule

Children at ages 15 months and 4 years.

Adults who are susceptible to one or more of measles, mumps and rubella. Susceptible adults are:

  • individuals born from 1 January 1969 with no documented history of 2 doses of measles-containing vaccine after age 12 months
  • individuals with no documented measles IgG antibody.

For (re-)vaccination following immunosuppression (if the individual is immunocompetent enough to safely receive the vaccine).

Vaccine efficacy/ effectiveness Measles vaccines are highly efficacious, and immunisation programmes have controlled measles to the point of elimination in many populations.
Egg allergy Egg allergy, including anaphylaxis, is not a contraindication for MMR vaccine.
Adverse events to vaccine MMR vaccine is generally well tolerated. The risk of adverse reactions to MMR vaccine is low compared to the risk of complications from measles disease.
Public health measures

Notify the local medical officer of health immediately on suspicion.

Prevent measles transmission through exclusion and use of personal protective equipment.

Promote immunisation to susceptible individuals.

Management of contacts of measles cases should be discussed with the medical officer of health.

11.1 Virology

The measles virus is an RNA virus, from the genus Morbillivirus, in the family Paramyxoviridae. Humans are the only natural host for the measles virus. The virus is rapidly inactivated by sunlight, heat and extremes of pH.1

11.2 Clinical features

Measles is transmitted by direct contact with infectious droplets and also by airborne spread. It is one of the most highly communicable of all infectious diseases, with an approximate basic reproductive number of 12–18 in high-income countries2 (see section 1.2.1). There is a prodromal phase of two to four days with fever, conjunctivitis, coryza and Koplik’s spots on the buccal mucosa. The characteristic maculopapular rash classically appears first behind the ears on the third to seventh day, spreads over three to four days from the head and face, over the trunk to the extremities. It lasts for up to one week. The patient is most unwell during the first day or two after the appearance of the rash.

The incubation period is about 10 days, but may be 7 to 18 days from exposure to onset of fever. It may be longer in those given IG after exposure. Measles is highly infectious from five days before to five days after rash onset, counting the day of rash onset as day one.

Complications are common, occurring in 10 percent of cases, and include otitis media, pneumonia, croup and diarrhoea. Encephalitis has been reported in 1 in every 1,000 cases, of whom some 15 percent die and a further 25–35 percent are left with permanent neurological damage. Other complications of measles include bronchiolitis, sinusitis, myocarditis, corneal ulceration, mesenteric adenitis, hepatitis and idiopathic thrombocytopenic purpura (ITP or immune thrombocytopenia).

Sub-acute sclerosing panencephalitis, a rare degenerative central nervous system disease resulting from persistent measles virus infection, is fatal. Sub-acute sclerosing panencephalitis typically occurs 7 to 11 years after wild-type measles virus infection.3 This complication has virtually disappeared where there is widespread measles immunisation.

The case fatality rate for reported cases of measles in the US is 1–3 per 1,000.3 Measles is particularly severe in the malnourished, children with vitamin A deficiency, and in patients with defective cell-mediated immunity, who may develop giant cell pneumonia or encephalitis without evidence of rash, and have a much higher case fatality rate. Measles during pregnancy can cause miscarriage, stillbirth and preterm delivery.1

Measles is also serious in healthy children: over half of all the children who died from measles in the UK between 1970 and 1983 were previously healthy.4 No other conditions were reported as contributing to the death of seven people who died from measles in the 1991 New Zealand epidemic.

11.3 Epidemiology

11.3.1 Global burden of disease

Mortality and morbidity

From 2000 to 2015, the annual reported measles incidence decreased by 75 percent worldwide, from 146 to 36 cases per million population, due to increased vaccine coverage. Annual estimated measles deaths decreased by 79 percent, from 651,600 cases to 134,200.5

Although measles mortality rates have fallen significantly,6 measles remains an important vaccine-preventable cause of death among children throughout the world, particularly in low-income countries. The disease is highly infectious in non-immune communities, with epidemics occurring approximately every second year.

Measles elimination

When a country is verified by the Measles Regional Verification Commission as having eliminated measles, it means that the country interrupted transmission of the endemic strain of circulating measles virus for a period of 36 months. Importations of measles virus may have occurred during this period, but circulation of the imported strains of measles virus was interrupted within 12 months of the importation.7

In May 2012 the 194 member states of the World Health Assembly endorsed the Global Vaccine Action Plan 2011–2020,8 which aims to eliminate measles in at least four WHO regions by 2015 and in five WHO regions by 2020. In September 2016, the Region of the Americas was the first WHO region to be declared free of measles. New Zealand has not yet been verified as having eliminated measles.

11.3.2 New Zealand epidemiology

Measles vaccine was introduced in 1969 and moved to a two-dose schedule (as MMR vaccine) in 1992. Measles became a notifiable disease in 1996. The current two-dose schedule at ages 15 months and 4 years was introduced in 2001 (see Appendix 1 for more information about the history of the Schedule).

The most recent measles epidemics occurred in 1991 (the number of cases was estimated to be in the tens of thousands) and 1997 (2,169 cases identified).

Smaller outbreaks occurred in 2009, 2011, 2014 and 2016 (see Figure 11.1). The largest outbreak was in 2011 and mainly affected Auckland, with 489 confirmed or probable cases. It started with an unimmunised child who became infected on a family trip to England, then developed measles when back in Auckland. Many of the secondary cases were in unimmunised high school children and young adults. The outbreak officially ended in July 2012.9

Importation of measles by non-immune people who had travelled overseas was also linked to the measles outbreaks in New Zealand in 2014 and 2016 (see also section 11.5.5).

Figure 11.1: Number of measles notifications by month reported, January 2006 to December 2016
Figure 11.1: Number of measles notifications by month reported, January 2006 to December 2016

Note: 2016 data is provisional.

Source: ESR

To eliminate measles epidemics, modelling suggests that New Zealand needs to achieve a coverage level of greater than 90 percent for both doses of MMR.10 If this coverage level is achieved and maintained, the length of time between epidemics will increase and may lead to the elimination of measles. As at 31 December 2016, the 5-year-old immunisation coverage rate, which includes two doses of measles-containing vaccine, was 88.6 percent – close to the target. However, previous years of low vaccine coverage have resulted in sufficient numbers of non-immune adolescents and young adults to permit outbreaks to occur.

11.4 Vaccines

11.4.1 Available vaccines

The measles vaccine is only available as one of the components of MMR vaccine. This vaccine is a freeze-dried preparation containing live attenuated measles, mumps and rubella viruses.

Funded vaccine
Other vaccines

MMR II (MSD) was the funded vaccine prior to the 1 July 2017 Schedule change. It contains:

Two quadrivalent measles, mumps, rubella and varicella vaccines (MMRV, see chapter 21) are also registered but not currently available in New Zealand:

11.4.2 Efficacy and effectiveness

Measles vaccines are highly efficacious, and immunisation programmes have controlled measles to the point of elimination in many populations.11 Outbreaks and epidemics continue to occur where low immunisation rates and/or sufficient numbers of susceptible members of communities are present. A 2012 Cochrane review of the safety and effectiveness of MMR vaccine concluded that a single dose of MMR vaccine is at least 95 percent effective in preventing clinical measles and 92 percent effective in preventing secondary cases among household contacts aged 6 months and older.12 This was a systematic review of clinical trials and studies, which involved approximately 14.7 million children.

Seroconversion to all three viruses of MMR vaccine occurs in 85–100 percent of recipients. ‘Primary vaccine failure’ refers to the lack of protective immunity despite vaccination. It is due to failure of the vaccine to stimulate an immune response. This occurs in 5–10 percent of recipients after the first dose and is rare after a second dose. More than 99 percent of people who receive two MMR doses (given at least four weeks apart, and the first dose given after age 12 months) develop serologic evidence of immunity to measles.3 Two doses are required for measles control and elimination in populations.3 The second MMR dose is not a booster, it is given to address primary vaccine failure.

Measles vaccination may have nonspecific effects, reducing mortality from other infectious diseases. Infection with the measles virus may cause immune memory loss and predispose people to opportunistic infections for up to three years.13 Population-level data from the UK, US and Denmark indicates that when measles was common, measles virus infections could have been implicated in as many as half of all childhood deaths from infectious disease.13 The authors suggest that the reduction in measles infections was the main factor in reducing overall childhood infectious disease mortality after the introduction of vaccination.

Duration of immunity

Even though antibody levels decline over time, secondary vaccine failure (ie, vaccine failure due to waning of protective immunity) has only rarely been documented for measles and rubella, but recently there have been outbreaks thought to be due to declining vaccine-induced mumps immunity.14

In Finland in 1982 a cohort was recruited at the start of the national MMR vaccination programme to study the persistence of vaccine-induced antibodies. By the mid-1990s Finland had eliminated measles, mumps and rubella, and there was little opportunity for natural boosting to occur. The follow-up of this cohort has shown that while antibodies wane over time, 20 years after the second MMR dose immunity to rubella was secure, 95 percent of people remained sero‑positive for measles and immunity to mumps declined, with 74 percent being sero-positive.15 The antibody avidity also decreased over time, by 8 percent for measles and 24 percent for mumps.16

Waning of both the concentration and the avidity of antibodies might contribute to measles and mumps infections occurring in individuals who have received two doses of MMR.

See section 21.4.2 for efficacy and effectiveness data for VV.

11.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.17 Store at +2°C to +8°C. Do not freeze.

MMR vaccine must be reconstituted only with the diluents supplied by the manufacturer. Use MMR vaccine as soon as possible after reconstitution. If storage is necessary, reconstituted MMR vaccine can be stored at +2°C to +8°C for up to eight hours.

11.4.4 Dosage and administration

The dose of MMR is all of the reconstituted vaccine (approximately 0.5 mL) administered by subcutaneous injection (see section 2.2.3).

Co-administration with other vaccines

MMR vaccine can be given concurrently with other vaccines, as long as separate syringes are used and the injections are given at different sites. If not given concurrently, live vaccines should be given at least four weeks apart. (See also section 2.2.7 for information about multiple injections at the same visit.)

Interchangeability

The two brands of MMR vaccine (Priorix and MMR II) may be used interchangeably for completion of a course.18

11.5 Recommended immunisation schedule

Table 11.1: Recommended MMR vaccine schedule
  Schedule
Usual childhood schedulea 2 doses: at ages 15 months and 4 years
Catch-upb for children, adolescents and adults 2 doses: at least 4 weeks apart
  1. If MMR is given to children aged 6–12 months for outbreak control, 2 further MMR doses are still required at ages 15 months and 4 years.
  2. For those born from 1 January 1969 who do not have documented evidence of two doses of an MMR-containing vaccine given after age 1 year, or who do not have serological evidence of protection for measles, mumps and rubella. See section 11.5.2.

11.5.1 Usual childhood schedule

MMR vaccine is recommended irrespective of a history of measles, mumps or rubella infection or measles immunisation. A clinical history does not reliably indicate immunity unless confirmed by serology. There are no known ill effects from vaccinating children, even if they have had serologically confirmed infection with any of the viruses.

Measles vaccine is recommended as MMR at age 15 months and at age 4 years. Two doses of measles vaccine are recommended because nearly all of the 5–10 percent who fail to be protected by the first dose will be protected by the second. The second dose of measles vaccine can be given as soon as four weeks after the first dose.

MMR vaccine may be given to children aged 12 months or older whose parents/guardians request it, and no opportunity should be missed to achieve immunity. If MMR is given early (ie, at 12 months of age), the vaccinator may also give the other scheduled 15-month vaccinations. This would reduce the risk of the child not returning for the other 15‑month vaccinations.

MMR vaccine when aged under 12 months

MMR may be recommended for infants aged 6–12 months during measles outbreaks if cases are occurring in the very young (see section 11.8). These children still require a further two doses of MMR at ages 15 months and 4 years because their chance of protection from measles is lower when the vaccine is given when they are aged under 12 months. Any recommendations will be made by the local medical officer of health and the Ministry of Health based on local epidemiology. Note: Some immigrant children may have received a measles-containing vaccine when aged under 12 months.

11.5.2 Catch-up

Two doses of MMR (at least four weeks apart) are recommended and funded for any child, adolescent or adult who is known to be susceptible to one or more of the three diseases.

Adults born in New Zealand before 1969 are considered to be immune to measles as circulating virus and disease was prevalent prior to the introduction of measles vaccine in 1969.

Adults born from 1 January 1969

All individuals born in 1969 or later who do not have documented evidence of two doses of an MMR-containing vaccine given after age 1 year (even if they have received two doses of a measles-containing vaccine) or who do not have serological evidence of protection for measles, mumps and rubella should be considered susceptible.

This particularly applies to:

Some adults may have received one dose of measles vaccine and one dose of MMR during one of the catch-up campaigns (eg, the 1997 campaign, when all those aged up to 10 years were offered MMR vaccine). They will have therefore received the recommended two doses of measles, but only one of mumps and rubella. While the main reason for a two-dose MMR schedule is to protect against measles, two doses of all three antigens is recommended and funded. These individuals can receive a second dose of MMR (ie, a third dose of measles vaccine) without any concerns. It is important that women of childbearing age are immune to rubella (see chapter 18).

All persons born from 1 January 1969 with only one documented dose of prior MMR should receive a further dose of MMR; if there are no documented doses of prior MMR, then two doses should be administered, at least four weeks apart.

11.5.3 Immunocompromise

In general, MMR is contraindicated in immunocompromised individuals (see section 4.3). They can be partially protected from exposure to infection by ensuring that all contacts are fully immunised, including hospital staff and family members. There is no risk of transmission of MMR vaccine viruses from a vaccinee to the immunocompromised individual. See section 11.7.2.

MMR vaccine is funded for (re-)vaccination following immunosuppression. However, it is important to be sure that the individual is immunocompetent enough to safely receive the vaccine.

HIV infection

Discuss vaccination of individuals with HIV infection with their specialist (see ‘HIV infection’ in section 4.3.3).

MMR vaccine is recommended for all HIV-positive children, whether symptomatic or asymptomatic, if the CD4+ lymphocyte percentage is 15 percent or greater. Asymptomatic children who are not severely immunocompromised are recommended to receive MMR vaccine from age 12 months to provide early protection against the three diseases. Susceptible HIV-positive children and adults aged 14 years and older may receive MMR vaccine if the CD4+ lymphocyte count is 200 cells/mm3 or greater. Administration of MMR with CD4+ counts below these recommended levels has been associated with vaccine-related pneumonitis (from the measles component).3

11.5.4 Pregnancy and breastfeeding

MMR vaccine is contraindicated during pregnancy. Pregnancy should be avoided for four weeks after MMR vaccination.1, 3

MMR vaccine can be given to breastfeeding women.

(See also sections 4.1 and 18.5.3.)

11.5.5 Travel

International travel is an important factor in reintroducing measles into New Zealand, and so vaccination with a measles-containing vaccine should be considered for all children and adults travelling overseas if they have not previously been adequately vaccinated.

Measles remains endemic in many countries, including areas in Europe, Asia, the Pacific and Africa. Of the 159 measles cases reported in the US from January to April 2015, 153 (96 percent) were import-associated.19 Travel was also linked to the measles outbreaks in New Zealand in 2011, 2014 and 2016.

11.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general vaccine contraindications.

11.6.1 Contraindications

The general contraindications that apply to all immunisations are relevant to MMR vaccine (eg, children with an acute febrile illness should have their immunisation deferred).

Anaphylaxis following a previous dose of MMR or any of the vaccine components is a contraindication to a further dose of MMR. Individuals who have anaphylaxis after receiving MMR should be serologically tested for immunity and referred to, or discussed with, a specialist if non-immune to rubella or measles.

MMR is contraindicated for:

11.6.2 Precautions

Children with a history of seizures should be given MMR, but the parents/guardians should be warned that there may be a febrile response. Children with current ITP should have the timing of vaccination discussed with the specialist responsible for their care.

Women of childbearing age should be advised to avoid pregnancy for the next four weeks1, 3 after MMR vaccination (see section 18.5.3).

Measles vaccination may temporarily suppress tuberculin skin test (TST/Mantoux) reactivity, so if required, TST should be placed on the same day as MMR vaccination or postponed for four to six weeks after vaccination.3 TST is not a prerequisite for measles vaccination. An individual with active TB should be established on treatment before administering MMR vaccine.

11.6.3 Egg allergy

The measles and mumps components of the MMR vaccine are manufactured in chick embryo cell culture, so there may be trace amounts of egg protein in the vaccine. However, egg allergy, including anaphylaxis, is not a contraindication to measles-containing vaccines. Various studies have confirmed children with egg allergy can be vaccinated safely.3, 20, 21 Other components of the vaccine may be responsible for allergic reactions.22 Individuals with egg allergy may therefore be safely vaccinated in primary care.23

11.7 Expected responses and AEFIs

11.7.1 Expected responses

A fever of 39.4°C or more occurs in 5–15 percent of children 6 to 12 days after immunisation and generally lasts one to two days.3 Rash occurs in approximately 5 percent of children at the same interval post-vaccination: these children are not infectious to others.3 The majority of these events are coincidental and not caused by the vaccine.24 Serological tests or PCR can be expected to be positive if performed during this time, so testing should not be routinely performed.

The mumps vaccine may produce parotid and/or submaxillary swelling in about 1 percent of vaccinees, most often 10 to 14 days after immunisation.25 The rubella vaccine can cause a mild rash, fever, lymphadenopathy and joint pain between one and three weeks after immunisation.26 There were no persisting sequelae associated with the administration of three million doses of MMR to 1.5 million children in Finland.24, 27

11.7.2 AEFIs

Temporally related reactions, including febrile seizures, nerve deafness, aseptic meningitis, encephalitis, rash, pruritus, and purpura, may follow immunisation rarely; however, causality has not been established.28

Vaccine virus transmission

MMR vaccine viruses have been regarded as being non-transmissible from vaccinees. There are two poorly documented case reports of transmission: one of rubella and one of a mumps vaccine strain from a vaccine that is no longer in production.29 Following immunisation with both measles and rubella vaccines, live virus has been isolated rarely from pharyngeal secretions.30, 31 There have been no confirmed cases of disease transmission from MMR vaccine viruses.

Idiopathic thrombocytopenic purpura (ITP)

MMR vaccine is the only childhood vaccine with an elevated risk of ITP, which occurs in 1 in 22,000 to 40,000 people, 15 to 35 days after immunisation.3 A review of data from 1.8 million children in the US found 197 cases of ITP, with an incidence risk ratio of 5.48 (95% CI: 1.61–18.64) in the 1 to 42 days after vaccination.32 If ITP occurs, measles, mumps and rubella serology should be measured, and if the individual is immune to all three infections, a second dose is not required. However, if the individual is susceptible to any of the three infections, a second dose should be administered.33, 34, 35 The risk of thrombocytopenia is higher after the first dose of vaccine than after the second dose.3

11.7.3 Adverse outcomes not linked to MMR

There have been multiple epidemiological studies published from the UK,36 Finland37 and elsewhere38, 39 confirming that there is no link between MMR vaccine and the development of autism in young children (see section 3.2.4 for further discussion on this issue).

11.8 Public health measures

11.8.1 Diagnosis

A single case of measles should be considered an outbreak and result in a suitable outbreak response. Practitioners should have a low index of suspicion for notification, and all suspected clinical cases should be isolated immediately and notified to the medical officer of health.

The standard clinical case definition for measles is ‘an illness characterised by all of the following: generalised maculopapular rash, starting on the head and neck; fever (at least 38°C if measured) present at the time of rash onset; cough or coryza or conjunctivitis or Koplik’s spots present at the time of rash onset’.

It is important that the diagnosis be laboratory confirmed, as many viral infections can mimic measles. In the first instance, a nasopharyngeal and throat swab should be taken for viral identification by PCR. Further testing should be discussed with a clinical microbiologist. For instructions on measles specimen collection and transport, see the National Measles Laboratory website (www.measles.co.nz).

11.8.2 Prophylaxis

MMR vaccine

There is evidence that a single dose of MMR vaccine when given to an unvaccinated person within 72 hours of first contact with an infectious person may reduce the risk of developing disease.1 If there is doubt about vaccination status, MMR should still be given. MMR will not exacerbate the symptoms of measles if a person is already incubating the disease, but in these situations, any measles-like illness occurring shortly after vaccination is likely to be due to infection.

If MMR vaccine is not given within 72 hours of first exposure, it should still be offered at any interval in order to offer protection from future exposures, unless the vaccine is contraindicated.

In an outbreak affecting infants, the use of MMR vaccine for infants aged 6–14 months should be considered. If MMR vaccine is given to an infant aged under 12 months, two more doses are still required after age 12 months and at least four weeks apart. This is because the seroconversion rate is lower when MMR is administered to an infant aged under 12 months. In an outbreak affecting young children, the second MMR vaccine does not have to be delayed until 4 years of age but can be given at any time from four weeks after the first dose.

Human normal immunoglobulin prophylaxis for contacts

Human normal immunoglobulin is recommended for measles-susceptible individuals in whom the vaccine is contraindicated (see section 11.6) and susceptible pregnant contacts. For these individuals, human normal immunoglobulin is given to attenuate disease and should be given as soon as possible, up to a maximum of six days after exposure. All other susceptible contacts should be offered MMR as post-exposure prophylaxis (as described above). Infants aged under 6 months where there is evidence of maternal immunity do not require any prophylaxis, but will still need the scheduled MMR doses at ages 15 months and 4 years.

Human normal immunoglobulin may be recommended for the following contacts of measles cases as soon as possible and up to six days after exposure:

The recommended doses as follows.

Prophylaxis with intravenous immunoglobulin

IVIG (Intragam P) can be considered for immunosuppressed and immune-deficient measles contacts (who may, for example, have a central venous catheter), individuals with reduced muscle bulk, or in those people for whom large doses are required (see Appendix 6 for more information about passive immunisation).

The recommended dose of IVIG is 0.15 g/kg. See the guidance from the Health Protection Agency for further information (www.gov.uk/government/publications/measles-post-exposure-prophylaxis).

If there are further queries, these can be directed to the New Zealand Blood Service medical team via the DHB blood bank.

11.8.3 Exclusion

Parents/guardians should be advised that children who are suspected or confirmed measles cases should be excluded from early childhood services, school or community gatherings until at least five days after the appearance of the rash.

Immune contacts (ie, children aged 12 months to under 4 years who have received one dose of measles-containing vaccine after their first birthday and children aged 4 years and older who have received two doses) need not be excluded from these settings. Non-immune (susceptible) contacts should be excluded because of the risk of developing the disease themselves, and the risk of passing on the disease during the prodromal phase to other susceptible children. Advise susceptible contacts to avoid attending school, early childhood services or community gatherings, and to avoid contact with other susceptible individuals, until 14 days after the last exposure to the infectious case.

Given that post-exposure MMR vaccination cannot guarantee protection, susceptible contacts who have received their first MMR vaccination within the 72-hour period after first exposure should also be excluded for 14 days after the last exposure to the infectious case (unless they subsequently meet the criteria for immunity). Contacts who have previously received one documented dose of MMR and then receive their second dose of MMR within 72 hours after first exposure can go back to school or work. If contacts receive their second MMR more than 72 hours after exposure, they should be excluded for 14 days after the last exposure to a person with measles.

Individuals who have received IG prophylaxis should also be excluded for 14 days after the last exposure to the infectious case.

For more details on control measures, refer to the ‘Measles’ chapter of the Communicable Disease Control Manual 2012.40

11.9 Variations from the vaccine data sheet

The vaccine data sheet recommends a single dose of MMR vaccine. However, as 5–10 percent of recipients fail to seroconvert after the first dose (see section 11.4.2), the Ministry of Health recommends and funds a second dose of MMR vaccine. Two doses are required for measles control and elimination;3 the second MMR dose is not a booster.

The vaccine data sheet states that pregnancy should be avoided for three months after vaccination. The Ministry of Health advises that women of childbearing age should avoid pregnancy for the next four weeks1, 3 after MMR vaccination.

The vaccine data sheet states that individuals who have experienced anaphylaxis after egg ingestion should be vaccinated with extreme caution, with adequate treatment for anaphylaxis on hand should such a reaction occur. However, various studies have confirmed that egg-allergic children can be vaccinated safely.3, 20, 21 The Ministry of Health recommends that individuals with egg allergy, including anaphylaxis, may be safely vaccinated in primary care (see section 11.6.3).

References

  1. Strebel PM, Papania MJ, Fiebelkorn AP, et al. 2013. Measles vaccine. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  2. Fine PEM, Mulholland K. 2013. Community immunity. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  3. American Academy of Pediatrics. 2015. Measles. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  4. Miller CL. 1985. Deaths from measles in England and Wales, 1970–83. British Medical Journal 290(6466): 443–4.
  5. Patel MK, Gacic-Dobo M, Strebel PM, et al. 2016. Progress toward regional measles elimination – worldwide, 2000–2015. Morbidity and Mortality Weekly Report 65(44): 1228–33. URL: https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6544a6.pdf (accessed 14 November 2016).
  6. GBD 2015 Child Mortality Collaborators. 2016. Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388(10053): 1725–74. URL: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31575-6/fulltext (accessed 14 November 2016).
  7. World Health Organization. 2015. Measles Verification Q & A – March 2015. URL: http://www.wpro.who.int/mediacentre/releases/2015/final_rvc_measlesverificationqa.pdf?ua=1 (accessed 5 August 2016).
  8. World Health Organization. 2013. Global Vaccine Action Plan 2011–2020. URL: www.who.int/immunization/global_vaccine_action_plan/GVAP_doc_2011_2020/en/ (accessed 27 August 2013).
  9. Auckland Regional Public Health Service. 2012. Measles. URL: www.arphs.govt.nz/health-information/communicable-disease/measles (accessed 26 October 2013).
  10. Roberts MG. 2004. A Mathematical Model for Measles Vaccination. Unpublished report to the Ministry of Health, New Zealand.
  11. Zahraei SM, Gouya MM, Mokhtari Azad T, et al. 2011. Successful control and impending elimination of measles in the Islamic Republic of Iran. Journal of Infectious Diseases 204(Suppl 1): S305–11.
  12. Demicheli V, Rivetti A, Debalini MG, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database of Systematic Reviews 2012, Issue 2, Art. No. CD004407. DOI: 10.1002/14651858.CD004407.pub3 (accessed 27 August 2013).
  13. Mina MJ, Metcalf CJE, de Swart RL, et al. 2015. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science 348(6235): 694–99. DOI: 10.1126/science.aaa3662 (accessed 17 November 2016).
  14. Albertson JP, Clegg WE, Reid HD, et al. 2016. Mumps outbreak at a university and recommendation for a third dose of Measles-Mumps-Rubella vaccine — Illinois, 2015–2016. Morbidity and Mortality Weekly Report 65(29): 731–4. URL: https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6529a2.pdf (accessed 20 October 2016).
  15. Davidkin I, Jokinen S, Broman M, et al. 2008. Persistence of measles, mumps and rubella antibodies in an MMR vaccinated cohort: a 20-year follow-up. Journal of Infectious Diseases 197(7): 950–6.
  16. Kontio M, Jokinen S, Paunio M, et al. 2012. Waning antibody levels and avidity: implications for MMR vaccine-induced protection. Journal of Infectious Diseases 206(10): 1542–8.
  17. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  18. Department of Health and Ageing. 2016. Measles. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-9 (accessed 20 October 2016).
  19. Clemmons NS, Gastanaduy PA, Parker Fiebelkorn A, et al. 2015. Measles – United States, January 4–April 2, 2015. Morbidity and Mortality Weekly Report 64(14): 373–6. URL: http://www.cdc.gov/mmwr/pdf/wk/mm6414.pdf (accessed 5 August 2016).
  20. James JM, Burks W, Roberson P, et al. 1995. Safe administration of measles vaccine to children allergic to eggs. New England Journal of Medicine 332(19): 1262–6.
  21. Khakoo GA, Lack G. 2000. Recommendations for using MMR vaccine in children allergic to eggs. British Medical Journal 320(7239): 929–32.
  22. Fox A, Lack G. 2003. Egg allergy and MMR vaccination. British Journal of General Practice 53(495): 801–02. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314715/pdf/14601358.pdf (accessed 7 November 2016).
  23. Clark AT, Skypala I, Leech SC, et al. 2010. British Society for Allergy and Clinical Immunology guidelines for the management of egg allergy. Clinical & Experimental Allergy 40(8): 1116–29. URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2010.03557.x/epdf (accessed 9 November 2016).
  24. Peltola H, Heinonen OP. 1986. Frequency of true adverse reactions to measles-mumps-rubella vaccine. The Lancet 327(8487): 939–42.
  25. Rubin SA, Plotkin SA. 2013. Mumps vaccine. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  26. American Academy of Pediatrics. 2015. Rubella. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  27. Peltola H, Patja A, Leinikki P, et al. 1998. No evidence for measles mumps and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. The Lancet 351(9112): 1327–8.
  28. American Academy of Pediatrics. 2015. Mumps. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  29. Wolf J, Eisen JE, Fraimow HS. 1993. Symptomatic rubella reinfection in an immune contact of a rubella vaccine recipient. Southern Medical Journal 86(1): 91–3.
  30. Morfin F, Beguin A, Lina B, et al. 2002. Detection of measles vaccine in the throat of a vaccinated child. Vaccine 20(11–12): 1541–3.
  31. Reef SE, Plotkin SA. 2013. Rubella vaccine. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  32. O’Leary ST, Glanz JM, McClure DL, et al 2012. The risk of immune thrombocytopenic purpura after vaccination in children and adolescents. Pediatrics 129(2): 248–55.
  33. Beeler J, Varricchio F, Wise R. 1996. Thrombocytopenia after immunisation with measles vaccines: review of the vaccine adverse events reporting system (1990 to 1994). Pediatric Infectious Disease Journal 15(1): 88–90.
  34. Miller E, Waight P, Farrington CP, et al. 2001. Idiopathic thrombocytopenic purpura and MMR vaccine. Archives of Disease in Childhood 84(3): 227–9.
  35. Stowe J, Kafatos G, Andrews N, et al. 2008. Idiopathic thrombocytopenic purpura and the second dose of MMR. Archives of Disease in Childhood 93(2): 182–3.
  36. Miller E. 2002. MMR vaccine: review of benefits and risks. Journal of Infection 44(1): 1–6.
  37. Makela A, Nuorti JP, Peltola H. 2002. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 110(5): 957–63.
  38. Health Canada. 2001. Does measles-mumps-rubella (MMR) vaccination cause inflammatory bowel disease and autism? Canada Communicable Disease Report 27(8): 65–72.
  39. Davis RL, Kramarz P, Bohlke K, et al. 2001. Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease. Archives of Pediatric & Adolescent Medicine 155(3): 354–9.
  40. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).

12 Meningococcal disease

In this chapter:

Key information

12.1 Bacteriology

12.2 Clinical features

12.3 Epidemiology

12.4 Vaccines

12.5 Recommended immunisation schedule

12.6 Contraindications and precautions

12.7 Expected responses and AEFIs

12.8 Public health measures

12.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission By respiratory droplets or direct contact with nasopharyngeal secretions from a carrier or case.
Incubation period 2–10 days, commonly 3–4 days.
Period of communicability Therapy with cefotaxime, ceftriaxone, rifampicin, or ciprofloxacin eradicates N. meningitidis from mucosal surfaces within 24 hours, and the case is no longer considered infectious.
Available vaccines

Meningococcal group C conjugate (MenCCV):

  • NeisVac-C.

Quadrivalent meningococcal conjugate (MCV4):

  • Menactra (MCV4-D) – conjugated to diphtheria toxoid
  • Nimenrix (MCV4-T) – conjugated to tetanus toxoid.
Dose, presentation, route

0.5 mL per dose.

Presentation:

  • MenCCV: pre-filled syringe
  • MCV4-D: vial
  • MCV4-T: vaccine vial and pre-filled syringe. MCV4-T must be reconstituted before use.

Intramuscular injection.

Funded vaccine indications

MCV4-D (Menactra) or MenCCV (NeisVac-C) for:

  • patients pre- or post-splenectomy or with functional asplenia
  • patients with HIV, complement deficiency (acquired, including monoclonal antibody therapy against C5, or inherited) or pre- or post-solid organ transplant
  • HSCT (bone marrow transplant) patients
  • patients following immunosuppression
  • close contacts of meningococcal cases (of relevant serotype).
Vaccine efficacy/ effectiveness

MenCCV: 83–100% effectiveness. Marked reduction in disease incidence when used in population-wide programmes. Immunity wanes with time.

MCV4: 80–85% effectiveness; 2–5 years after vaccination, effectiveness wanes to 50–60%.

Public health measures

Cases: must be notified upon suspicion. Administer antibiotics as soon as possible, often prior to transfer to hospital.

Contacts: administer antibiotic prophylaxis preferably within 24 hours of the initial diagnosis, but recommended up to 14 days after the diagnosis of illness.

12.1 Bacteriology

Meningococcal disease is caused by Neisseria meningitidis, a gram-negative bacterium, and is an important cause of sepsis and meningitis. Worldwide, the most important serogroups of meningococci are groups A, B, C, W135 and Y. Groups B and C are the most important types seen in children and young adults in New Zealand. Group A is an important epidemic strain, particularly in Africa and the Middle East. Serotype distribution patterns differ between countries. W135 and Y group organisms are seen as rare causes of bacteraemia and pneumonia in the elderly.

Spread from person to person is by respiratory droplets or direct contact with nasopharyngeal secretions, from a carrier or case.

12.2 Clinical features

Table 12.1 below describes the symptoms and signs of meningococcal disease – individuals may present with some or all of these. Meningococcal bacteraemia is more common than meningitis, and the illness may be a mild non-specific illness or a rapidly progressive illness with fatal outcome.

Table 12.1: Symptoms and signs of meningococcal disease
Adolescents and adults Young infants and children

Sepsis syndrome

Nausea

Vomiting

Meningism

Rash – petechial or purpuric or maculopapular;
a rash may not be present in the early stages of the disease and is absent in about one-third of cases

Sleepy, difficult to rouse

Arthralgia and myalgia

Occasionally in young adults, irrational behaviour

As for adolescents and adults, plus the following:

  • bulging fontanelle
  • tachycardia
  • altered responsiveness
  • irritability and/or floppiness
  • refusing drinks or feeds
  • poor peripheral perfusion
Notify all suspected cases as soon as possible to the local medical officer of health. This includes out-of-hours notification.

Meningococcal disease covers a spectrum, from chronic septic arthritis and minor rash to fulminant sepsis and meningitis. Classic meningococcal sepsis frequently presents with sudden onset of fever and rash. Septic shock may rapidly ensue. Meningitis can occur with and without signs of sepsis. In fulminant cases, disseminated intravascular coagulation, shock, coma and death can occur within a few hours despite appropriate treatment.

Because of the fulminant nature of meningococcal sepsis, antibiotics (Table 12.2) should be administered as soon as possible, often prior to transfer to hospital. Antibiotics given prior to transfer should be clearly noted on the clinical information that accompanies the patient to hospital.

Table 12.2: Recommended antibiotics for suspected cases
Antibiotic Dosage
Benzylpenicillin*

Adults: 1.2 g (2 MU) IV (or IM)

Children: 50 mg/kg IV (or IM)

Amoxycillin

Adults: 1–2 g IV (or IM)

Children 50 mg/kg IV (or IM)

*     Patients with a documented history of anaphylaxis to penicillin and who are suspected of suffering from meningococcal disease should be sent immediately to hospital without pre‑admission antibiotics.

12.3 Epidemiology

12.3.1 Global burden of disease

Incidence and serotypes

Introduction of a serogroup A conjugate vaccine has had a dramatic impact on disease in sub-Saharan Africa. Before the introduction the vaccine, Group A disease caused massive epidemics in sub-Saharan Africa (the ‘meningitis belt’), with incidence ranging from 10 to 25 per 100,000 during non-epidemic periods and up to 1,000 per 100,000 during epidemic years.1

The incidence in Canada, the US and Europe varies substantially by country, ranging from 0.18 per 100,000 to 3 per 100,000 persons per year.1 The serotype distribution varies by age, location and time, with types B, C and Y accounting for most of the reported cases.2 Group B disease is often the most common serotype causing infection, and can cause epidemics that start slowly and persist for five or more years. Group C meningococci have been associated with small clusters of meningococcal disease cases in schools and universities.

Risk groups

Those particularly at risk of meningococcal disease are children aged under 5 years, although all age groups can be infected. There is a higher case fatality rate in adults. Most infection occurs in healthy people, but those with a deficiency of terminal components of complement (C5–9), properdin deficiency or asplenia are at particular risk of recurrent meningococcal disease. Individuals with infection caused by an uncommon serogroup or recurrent disease should be investigated.

Close contacts of primary cases of meningococcal infection are at increased risk of developing infection, such as within families,3 early childhood education services, semi-closed communities, schools, correctional facilities and military recruit camps. Students living in hostel accommodation may also be at higher risk.4, 5, 6 In health care settings, only those with close exposure to oropharyngeal secretions of patients with meningococcal disease (as may occur during intubation or resuscitation) and microbiology laboratory workers are considered to be at increased risk.

It is not possible to calculate the incubation period for meningococcal disease for sporadic cases. Secondary cases (ie, in contacts of known cases of meningococcal disease) usually occur within four days, but it can be up to 10 days. The infectivity of patients with meningococcal disease is markedly reduced after 24 hours of antibiotic therapy, although treatment with cefotaxime, ceftriaxone, rifampicin or ciprofloxacin is necessary to reliably eradicate nasopharyngeal carriage and hence relax infection prevention and control precautions (see section 12.8.2).

In high-income countries, nasopharyngeal carriage of N. meningitidis occurs in approximately 10 percent of the overall population, rising from 2 percent in children aged under 4 years to a peak of 24.5 percent to 32 percent among 15–24-year-olds, then declining with increasing age.1 The relationship between risk factors for disease and those associated with carriage is incompletely understood.1 Carriage prevalence does not predict the disease incidence nor the occurrence or severity of outbreaks, as most of the carried strains are non-encapsulated and do not cause disease.1 Smoking, passive smoking, household crowding and upper respiratory tract infections increase carriage.

12.3.2 New Zealand epidemiology

Incidence and mortality

In 2015 the notification rate for meningococcal disease was 1.4 cases per 100,000 population, with a total of 64 cases notified (61 laboratory-confirmed).7 This was slightly higher than the 2014 rate (1.0 per 100,000, 45 cases), but significantly lower than the peak rate experienced during the meningococcal disease epidemic (overall 16.7 per 100,000 but 200 per 100,000 in children under 12 months) in 2001. The annual number of notified cases of meningococcal disease in New Zealand since 1970 is shown in Figure 12.1. The epidemic from 1991 to 2007 was largely due to a single Group B subtype (B:4:P1.7b,4).

Figure 12.1: Notified cases of meningococcal disease,
1970–2015
Figure 12.1: Notified cases of meningococcal disease, 1970–2015

Source: ESR

Meningococcal infection rates remain consistently higher in Māori and Pacific peoples compared with the total population. Māori had the highest disease rate in 2015 (2.9 per 100,000, 20 cases), followed by Pacific peoples (2.8 per 100,000, 8 cases).7

Household crowding is an important risk factor for meningococcal disease, independent of ethnicity.8

In 2015 the highest age-specific disease rates were among those aged under 1 year (22 per 100,000, 13 cases) and 1–4 years (6.9 per 100,000, 17 cases).7

Figure 12.2 shows the age distribution of the 320 strain-typed cases from 2011 to 2015. Group B strains were the most prevalent in all age groups except for the age group 15–19 years, in which Group C strains were the most prevalent.

Figure 12.2: Age distribution among strain-typed meningococcal disease cases, 2011–2015 cumulative data
Figure 12.2: Age distribution among strain-typed meningococcal disease cases, 2011–2015 cumulative data

Note: Other includes 2 cases with non-groupable strains (1 each in the <1 and 20+ age groups) and 1 case with a group 29E strain (in the <1 age group).

Source: ESR

Almost all cases (62/64) in 2015 were hospitalised. Four deaths were reported, giving a case fatality rate of 6.3 percent.7

Strain types

Strain type was determined for 59 of the 61 laboratory-confirmed cases.7 Group B strains were the most prevalent in 2015, causing 69 percent of the confirmed cases (Figure 12.3). The group B strain (B:4:P1.7b,4) responsible for the epidemic caused 17 percent of all meningococcal disease in 2015 (10 of the 59 typed cases). The number of cases of meningococcal disease caused by group C strains has decreased since 2011 (Figure 12.3).

Figure 12.3: Groups and dominant subtypes among strain-typed meningococcal disease cases, 2011–2015
Figure 12.3: Groups and dominant subtypes among strain-typed meningococcal disease cases, 2011–2015

Note: Not shown in the figure are 2 cases with non-groupable strains (1 each in 2011 and 2013), and 1 case in 2014 with a group 29E strain.

Source: ESR

12.4 Vaccines

12.4.1 Introduction

Internationally, meningococcal vaccination programmes have been revolutionised by the development of conjugate vaccines, which allow vaccination in younger children and are associated with the development of herd immunity when used widely (see section 1.4.3 for more information about conjugate vaccines).

The monovalent (C) and quadrivalent (ACYW135) conjugate vaccines contain CRM197 or diphtheria or tetanus toxoid conjugate and are currently the only meningococcal vaccines available in New Zealand that can be effectively used in children aged under 2 years. Polysaccharide vaccines can offer three to five years’ protection in adults, but they are generally regarded as inferior to conjugate vaccines. There are no polysaccharide vaccines registered (approved for use) and available (marketed) in New Zealand at the time of writing. Vaccination against serogroups other than C (except serogroup B, which is not available in a conjugate vaccine) does not really offer much advantage in the New Zealand context, but those travelling to Africa, the Middle East and other areas with different serotype prevalence may benefit from broader protection. The meningococcal vaccines registered and available in New Zealand are summarised in Table 12.3 below.

Table 12.3: Meningococcal vaccines registered and available in New Zealand
Name (manufacturer) Vaccine type
NeisVac-C
(Pfizer NZ Ltd)
Meningococcal group C conjugate
(MenCCV)
Menactra
(Sanofi)
Quadrivalent meningococcal conjugate
(MCV4-D) (contains serogroups A, C, Y, and W135)
Nimenrix
(Pfizer NZ Ltd)
Quadrivalent meningococcal conjugate
(MCV4-T) (contains serogroups A, C, Y, and W135)
Funded vaccines

No meningococcal vaccines are included on the routine Schedule but meningococcal group C conjugate and quadrivalent meningococcal conjugate vaccines are recommended and funded for certain individuals (see section 12.5).

Other vaccines
Quadrivalent meningococcal conjugate vaccines

A second quadrivalent meningococcal conjugate vaccine MCV4-T (Nimenrix, Pfizer NZ Ltd) is registered and available in New Zealand for individuals aged 12 months to 55 years.

MCV4-T contains 5 µg of each polysaccharide derived from the capsules of group A, C, Y and W135 N. meningitidis strains, conjugated to 44 µg of tetanus toxoid carrier protein. Other components and excipients include sodium chloride, trometamol and sucrose.

Group B meningococcal vaccines

Group B vaccines are not currently registered in New Zealand. A strain-specific group B meningococcal vaccine (MeNZB, Chiron/Novartis) containing outer membrane vesicles derived from the epidemic strain B:4:P1.7b,4 (NZ 98/254) was developed for epidemic control in New Zealand and used between 2004 and 2008. The vaccination programme ceased in 2008 because of a decline in the incidence of group B disease.

The immune response to the vaccine was short lived and it is not expected that anyone previously vaccinated would still have existing immunity to B disease. This programme was covered in previous editions of the Handbook.

Since this time there have been major advances in group B vaccine development, and there are now two recombinant group B vaccines (4CMenB and 2CMenB), both of which cover a broad range of group B subtypes. Neither vaccine is currently available in New Zealand.

The 4CMenB recombinant vaccine (Bexsero) contains four components from the group B bacteria: three different group B surface proteins plus detoxified outer membrane vesicles from the New Zealand group B epidemic strain. The 4CMenB vaccine has large-scale clinical trial data to support its use, and licensure has been granted in Europe, Australia, Canada and the US. The 4CMenB vaccine is associated with more local and febrile reactions than some other childhood vaccines. No serious adverse events have been identified; however, febrile seizures have occurred in temporal association with this vaccine.9

The 2CMenB recombinant vaccine (Trumenba) contains two group B surface proteins. One protein from each factor H binding protein subfamily (A and B) is included in the vaccine. The immunogenicity and safety of 2CMenB was assessed in individuals aged 10 years and older who received the vaccine in studies conducted in the US, Europe and Australia. The vaccine was licensed in the US in October 2014. The most commonly reported side effects by those who received the 2CMenB vaccine were pain at the injection site, fatigue, headache, joint pain and chills.10

In February 2015 the US Advisory Committee on Immunization Practices recommended that individuals aged 10 years or older at increased risk for meningococcal disease should receive meningococcal B vaccine (either 4CMenB or 2CMenB).10 In June 2015, this recommendation was extended to include all adolescents and young adults aged 16–23 years (with a preferred age of 16–18 years), to provide short-term protection against most strains of serogroup B meningococcal disease.11 In September 2015 the UK introduced the 4CMenB vaccine as part of a funded schedule for infants.12 The vaccine is offered to infants at ages 2 and 4 months, with a booster at age 12 months.13

12.4.2 Efficacy and effectiveness

Meningococcal group C conjugate vaccines

The first national immunisation programme using a conjugate group C meningococcal vaccine was introduced in the UK in 1999. Group C conjugate vaccine was introduced into the UK infant immunisation schedule at ages 2, 3 and 4 months, as well as via a mass vaccination campaign up to age 20 years. Four years after introduction the overall reported effectiveness was at least 83 percent in children who had received the conjugate vaccine from age 5 months to 18 years.14 Data from that programme indicates that a booster dose in the second year of life is important for sustained protection following infant vaccination.

The meningococcal C programme introduced in the UK in 1999 was successful in reducing invasive disease meningococcal C to a very small number of cases.13 The routine schedule for protection against meningococcal C subsequently moved to a primary dose at age 12 months (as combined Hib-meningococcal C) and a booster at age 14 years (as MCV4).

Protective efficacy against carriage by adolescents of group C one year after the UK immunisation campaign was estimated at 69 percent.15 At the same time there was no increase in colonisation by the other meningococcal groups. Consistent with the reduction in meningococcal carriage rates, there has been a 67 percent reduction in group C disease among unvaccinated children within the target age groups and a reduction of 35 percent of cases in unvaccinated adults older than age 25 years.16 At the same time there was no evidence of capsular switching or an increase in disease caused by group B strains.17

The optimal vaccine schedule for sustained control of group C meningococcal disease by a universal programme has yet to be established. It is now recognised that circulating antibody is probably required for vaccine-induced protection and that antibody decay occurs quite rapidly in young children. Although conjugate vaccines can induce an anamnestic response, invasive disease develops within hours or days of acquisition and colonisation of the nasopharynx. This timeframe is shorter than that required for bactericidal antibodies to develop.

Herd protection, from reduced carriage resulting in reduced exposure to the organism, has an important role in the prevention of meningococcal disease. Consequently, further doses may be needed, possibly in early adolescence and then prior to leaving school. The exact timing will depend on any catch-up vaccination programme undertaken when the vaccine is first introduced, and the country’s specific epidemiology.

Quadrivalent meningococcal conjugate vaccines

An estimate of the effectiveness of the diphtheria conjugate quadrivalent meningococcal vaccine (MCV4-D, Menactra) among adolescents in the US was determined as 80–85 percent, which is similar to that reported for the polysaccharide vaccines.18 Estimates from a large case-control study in the US evaluating one of the two MCV4 vaccines, MCV4-D, suggest high vaccine effectiveness early after vaccination, but two to five years after vaccination, vaccine effectiveness wanes to 50–60 percent.1

The MCV4-D vaccine was poorly immunogenic in infants aged under 6 months,19 and it is currently registered in New Zealand for individuals aged 9 months to 55 years.

The MCV4-T vaccine (Nimenrix) is registered in New Zealand for individuals aged 12 months to 55 years. Clinical trials showed that the vaccine was immunogenic in children above the age of 12 months, adolescents, and adults, and has an acceptable reactogenicity and safety profile.20

Although both conjugate quadrivalent meningococcal vaccines available in New Zealand are licensed up to age 55 years, there was no published data for evidence of the effectiveness in older adults identified at the time of writing.

Quadrivalent meningococcal polysaccharide vaccines

These are not currently available in New Zealand. Conjugated quadrivalent vaccines are used in preference to polysaccharide vaccines.

12.4.3 Transport, storage and handling

Transport meningococcal conjugate vaccines according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.21 Store at +2°C to +8°C. MCV4-D and MCV4-T should be protected from light. Do not freeze.

Reconstitution

MCV4-T (Nimenrix) must be reconstituted with the supplied diluent and used as soon as possible.

12.4.4 Dosage and administration

Meningococcal group C conjugate vaccine (MenCCV)

Each MenCCV (NeisVac-C) dose is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

For healthy infants aged under 12 months, two doses are given at least eight weeks apart, with the first dose given not earlier than age 8 weeks. A booster is given in the second year of life. For healthy children, adolescents and adults, one dose is given. See Table 12.5 for schedules for at-risk individuals.

MenCCV can be administered concurrently with other scheduled vaccines, in separate syringes and at separate sites.

Quadrivalent meningococcal conjugate vaccines (MCV4)

Each MCV4 dose is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

Menactra (MCV4-D)

Menactra is registered in New Zealand for individuals aged 9 months to 55 years. For healthy children aged 9–23 months, two doses are given at least three months apart. For healthy individuals aged 2–55 years, one dose is given. See Table 12.5 for schedules for at-risk individuals.

MCV4-D can be concurrently administered with other vaccines in separate syringes and at separate sites,22, 23, 24, 25 except for PCV13. MCV4-D should be administered at least four weeks after PCV13. This is because when administered concurrently, there is impairment of the immune response to some of the pneumococcal serotypes.26, 27

Nimenrix (MCV4-T)

Nimenrix is registered in New Zealand for individuals aged 12 months to 55 years. One dose is given.

MCV4-T can be concurrently administered with other vaccines in separate syringes and at separate sites; however, there is no data on concurrent administration of MCV4-T and PCV13.

12.5 Recommended immunisation schedule

12.5.1 At-risk individuals

Meningococcal conjugate vaccines are not on the Schedule but are funded in special circumstances, as described in the shaded section of Table 12.4 below, with recommended dosing schedules in Table 12.5.

See sections 4.2 and 4.3 for more information about vaccination of special groups, including recommended immunisation schedules for high-risk individuals with certain medical conditions.

The conjugate vaccines are recommended (but not funded) for other individuals at risk, as described in Table 12.4.

Before travel

There are areas of the world where the risk of acquiring meningococcal infection is increased. Nevertheless, the risk to travellers to the developing world as a whole has been estimated as being less than one in a million per month. Recurrent epidemics of meningococcal disease occur in the sub-Saharan ‘meningitis belt’, from Senegal in the west to Ethiopia in the east, usually during the dry season (December to June). Epidemics are occasionally identified in other parts of the world and occurred recently in Saudi Arabia (during a Hajj pilgrimage), Kenya, Tanzania, Burundi, Mongolia and Nepal.

MCV4-D or MCV4-T are the preferred vaccines for travel. For website sources for information about meningococcal vaccines for travellers, see the WHO website (www.who.int/ith/en). Quadrivalent meningococcal vaccine is a requirement for pilgrims to the Hajj.

Before moving into communal living situations

Adolescents and young adults living, or planning to live, in communal accommodation such as a hostel, student accommodation, boarding school, in military accommodation, in correctional facilities or in other long-term institutions are likely to be at higher risk of acquiring meningococcal infection. Meningococcal vaccination should be considered.

Table 12.4: Meningococcal group C conjugate (MenCCV) and quadrivalent meningococcal vaccine (MCV4) recommendations

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to the funding decisions.

Recommended and funded

MenCCV and MCV4-D are recommended and funded for:

  • patients pre- or post-splenectomy or with functional aspleniaa,b
  • patients with HIV, complement deficiency (acquired, including monoclonal antibody therapy against C5, or inherited) or who are pre- or post-solid organ transplantb
  • HSCT (bone marrow transplant) patientsb
  • patients following immunosuppressionb,c
  • close contacts of meningococcal casesd
Recommended but not funded

MenCCV, MCV4-D or MCV4-T are recommended, but not funded, for individuals:

  • who are laboratory workers regularly handling meningococcal cultures
  • who are adolescents and young adults living in communal accommodation (eg, in a hostel or at boarding school, in military accommodation, in correctional facilities or in other long-term institutions).

MCV4-D or MCV4-T are recommended, but not funded, for individuals:

  1. Pneumococcal, Hib, influenza and varicella vaccines are also recommended for individuals pre- or post-splenectomy or with functional asplenia. See section 4.3.4.
  2. See sections 4.2 and 4.3 for more information.
  3. The period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days.
  4. Only one dose is funded for close contacts of meningococcal cases.
Table 12.5: Recommended meningococcal vaccine schedule for high-risk individuals (funded)

Note: See the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to the funding decisions.

Age at diagnosis Vaccine
(trade name)
Recommended vaccine schedule
Infants aged 6 weeks to under 12 months

MenCCV
(NeisVac-C)

and

Age-appropriate MenCCV schedule:

  • if aged under 6 months at diagnosis, give 2 doses 8 weeks apart, with a booster at age 12 months
  • if aged 6–11 months at diagnosis, give 1 dose, with a further dose at age 12 months.
MCV4-D (Menactra) At age 2 years, give 2 doses of MCV4‑Da 8 weeks apart, then a booster dose after 3 years, then 5‑yearly.
Children aged 12 months to under 18 years

MenCCV
(NeisVac-C) and

MCV4-D
(Menactra)

If aged 12–23 months at diagnosis, give 1 dose of MenCCV, followed by MCV4‑Da at age 2 years, 2 doses 8 weeks apart; then a booster of MCV4-D after 3 years, then 5‑yearly.

If aged ≥2 years at diagnosis, give 2 doses of MCV4-Da 8 weeks apart, and:

  • if the 1st MCV4-D dose was given at age <7 years, give a booster after 3 years, then 5‑yearly, or
  • if the 1st MCV4-D dose was given at age ≥7 years, give a booster dose every 5 years.
Adults aged 18 years and older MCV4-D
(Menactra)
Give 2 doses of MCV4-D, 8 weeks apart, then 1 dose every 5 years.a,b
  1. Give MCV4-D at least 4 weeks after PCV13.26, 27
  2. MCV4-D is registered for individuals aged 9 months to 55 years, but there are not expected to be any safety concerns when administered to adults older than 55 years.

12.5.2 Recommendations for children and adolescents

In the absence of a universal programme, non-high-risk children and adolescents may be offered meningococcal vaccines, but these are not funded. Table 12.6 suggests the most appropriate ages for this, reflecting the known ages of increased risk. The predominant meningococcal strains in New Zealand in childhood are B and C. There is no vaccine currently available in New Zealand for B. Particularly for those who are likely to travel, the quadrivalent vaccine is preferable because of the differing serotype patterns between countries, for example, the Y serotype is prominent in the US.

Table 12.6: Suggested meningococcal vaccines for children and adolescents (not funded)

Note: Vaccine immunity is not long-lasting. The suggested ages of vaccination are not expected to protect individuals through all of childhood, but are pragmatically focused on offering protection during the ages of highest risk. This does not apply to epidemic situations.

Age Vaccine options
(trade name)
Number of doses
<12 months MenCCV (NeisVac-C) 2 dosesa (primary course) plus a booster after 12 months of age
12 months to 2 years MenCCV (NeisVac-C), or
MCV4-D (Menactra) or MCV4-T (Nimenrix)
1 MenCCV, or
2 MCV4-Da,b doses or
1 MCV4-T
Early adolescence
(<16 years)
MenCCV (NeisVac-C) or
MCV4-D (Menactra) or MCV4-T (Nimenrix)
1 dose plus a booster at age 16–18
Late adolescence
≥16 years
MenCCV (NeisVac-C) or
MCV4-D (Menactra) or MCV4-T (Nimenrix)
1 dose, no booster required
  1. Refer to section 12.4.4 and the vaccine data sheets for the intervals between doses.
  2. MCV4-D should be administered at least 4 weeks after PCV13 (if used).26, 27

12.5.3 Pregnancy and breastfeeding

There are no reports of any adverse effects among pregnant women who have been vaccinated during pregnancy.26 The vaccine may be given to pregnant women if indicated.26 Meningococcal vaccine may be given to breastfeeding women.28

12.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

There are no specific contraindications for meningococcal vaccines, except for anaphylaxis to a previous dose or any component of the vaccine.

12.7 Expected responses and AEFIs

Frequent adverse reactions after meningococcal conjugate vaccines include localised pain, irritability, headache and fatigue.2, 20 Fever is reported by 2 to 5 percent of adolescents who receive MCV4-D.

12.7.1 Meningococcal group C conjugate vaccine

The most frequent response to MenCCV in the UK school programme was transient headache in 12 percent of students in the first three days after vaccination.29 This is more commonly reported by secondary students than primary school students. Mild to moderate local reactions at the injection site consisting of pain, tenderness and occasional redness were also reported. These peaked on the third day after the vaccine and resolved within a day.

A Cochrane Review assessed the safety of MenCCVs against group C disease.30 MenCCVs were shown to have an excellent safety profile in infants. The events more frequently reported in infants were fever (1–5 percent), irritability (38–67 percent), crying more than expected (1–13 percent), redness at the site of vaccination (6–97 percent), tenderness at the site of vaccination (11–13 percent), and swelling at the site of vaccination (6–42 percent).

The adverse events were similar in groups vaccinated with MenCCV and with the hepatitis B control vaccine, but following booster doses they were more frequent in the MenCCV group in one trial. Adverse events were rare. Anaphylaxis was reported at a rate of one per 500,000 doses distributed.29

12.7.2 Quadrivalent meningococcal conjugate vaccine

The safety of two doses of MCV4-D was assessed in a phase III trial of infants: dose one was administered at age 9 months and dose two was administered at age 12 months, with or without routine childhood vaccines.27 The percentage of participants with solicited systemic reactions after MCV4-D administration alone at age 12 months (60.6 percent) was lower than after the vaccination at age 9 months (68.2 percent), lower than the control groups at age 12 months (75.2–84.1 percent, depending upon the control vaccine), and lower than when MCV4-D was administered concurrently with the routine childhood vaccines (68.3–73.2 percent).

The safety profile of MCV4-T (Nimenrix) is very similar to other meningococcal conjugate vaccines.20

Guillain–Barré syndrome

There is no evidence of an association between meningococcal conjugate vaccines and GBS.28 An early report in the US of a suspected temporal association between MCV4-D (Menactra) and GBS was followed by a large retrospective cohort study in the US that found no evidence of an increased risk of GBS following administration of MCV4-D.31, 32 If indicated, meningococcal conjugate vaccines may be administered to individuals with a history of GBS.28

12.8 Public health measures

The overall rate of secondary cases in untreated adults is around 1 per 300. Adults and children in close contact with primary cases of invasive meningococcal infection are recommended to receive antibiotic prophylaxis, preferably within 24 hours of the initial diagnosis, but prophylaxis is recommended up to 14 days after diagnosis of illness.

Blood or cerebrospinal fluid culture is the main diagnostic method, but blood PCR may be useful if antibiotics are given without prior access to blood culture. It is recommended that in primary care three to five millilitres of blood should be taken in an ethylenediaminetetraacetic acid (EDTA) anticoagulant tube (usually with a purple top) prior to administration of antibiotics unless blood culture is available. This should accompany the patient to hospital.

12.8.1 Contacts

A contact is anyone who has had unprotected contact with upper respiratory tract or respiratory droplets from the case during the seven days before onset of illness to 24 hours after onset of effective treatment.33 Contacts at particular risk include:

Prophylaxis is not routinely recommended for health care personnel unless there has been intimate contact with oral secretions (eg, as a result of performing mouth-to-mouth resuscitation or suctioning of the case before antibiotic therapy has started).

12.8.2 Chemoprophylaxis for contacts

Recommended antibiotics

The recommended antibiotics are rifampicin, ceftriaxone or ciprofloxacin, preferably given within 24 hours of initial diagnosis, but prophylaxis is recommended up to 14 days after diagnosis of illness.

Rifampicin

The recommended dose of rifampicin is 10 mg/kg (maximum dose 600 mg) every 12 hours for two days. For infants aged under 4 weeks, the recommended dose is 5 mg/kg every 12 hours for two days.

Avoid rifampicin if pregnant or breastfeeding.

Ceftriaxone

A single dose of intramuscular ceftriaxone (125 mg for children aged under 12 years and 250 mg for older children and adults) has been found to have an efficacy equal to that of rifampicin in eradicating the meningococcal group A carrier state. Ceftriaxone is the drug of choice in a pregnant woman because rifampicin is not recommended later in pregnancy. Ceftriaxone may be reconstituted with lignocaine (according to the manufacturer’s instructions) to reduce the pain of injection. A New Zealand study demonstrated that ceftriaxone and rifampicin were equivalent in terms of eliminating nasopharyngeal carriage of N. meningitidis group B.34

Do not use in infants under aged under 4 weeks.

Ciprofloxacin

Ciprofloxacin given as a single oral dose of 500 mg or 750 mg is also effective at eradicating carriage. This is the preferred prophylaxis for women on the oral contraceptive pill and for prophylaxis of large groups.33

Ciprofloxacin is not generally recommended for pregnant and lactating women or for children aged under 18 years.35 Consult the manufacturer’s data sheet for appropriate use and dosage of ciprofloxacin in children.

Use of meningococcal conjugate vaccines for close contacts

Close contacts of cases of meningococcal disease may be offered the appropriate meningococcal conjugate vaccine (see section 12.5). See below for the use of the vaccines for the control of outbreaks, as initiated by the local public health service.

12.8.3 Outbreak control

When there is an outbreak of meningococcal disease of a specific vaccine group, an immunisation programme may be recommended and funded for a defined population. The local medical officer of health will determine the necessary action in discussion with the Ministry of Health.

For more details on control measures, refer to the ‘Neisseria meningitidis invasive disease’ chapter of the Communicable Disease Control Manual 2012.33

12.9 Variations from the vaccine data sheets

The MCV4-D data sheet states that the vaccine is indicated for use in individuals aged 9 months to 55 years. The Ministry of Health recommends that this vaccine may be used in adults aged over 55 years.28

The data sheet states that MCV4-D should be given as a single dose for individuals aged 2 years and older. The Ministry of Health recommends that two doses are given to individuals at high risk of meningococcal disease (see Table 12.5 and section 4.3), with booster doses every five years (if the first MCV4-D was given before age 7 years, give a booster after three years, then five-yearly).2

A history of GBS is listed as a precaution in the MCV4-D data sheet. However, there is no evidence of an association between meningococcal conjugate vaccines and GBS (see section 12.7.2).28 The Ministry of Health advises that, if indicated, MCV4-D may be administered to individuals with a history of GBS.28

The MenCCV data sheet states that the first dose of vaccine should not be given earlier than age 8 weeks. However, the Ministry of Health recommends that MenCCV may be given from age 6 weeks to infants at high risk of meningococcal disease (see Tables 12.4 and 12.5).

References

  1. Cohn A, MacNeil J. 2015. The changing epidemiology of meningococcal disease. Infectious Disease Clinics of North America 29(4): 667–77. DOI: http://dx.doi.org/10.1016/j.idc.2015.08.002 (accessed 3 December 2016).
  2. American Academy of Pediatrics. 2015. Meningococcal infections. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  3. Meningococcal Disease Surveillance Group. 1976. Analysis of endemic meningococcal disease by serogroup and evaluation of chemoprophylaxis. Journal of Infectious Diseases 134(2): 201–4.
  4. Neal KR, Nguyen-Van-Jam J, Jeffrey N, et al. 2000. Changing carriage rate of Neisseria meningitidis among university students during the first week of term: cross sectional study. British Medical Journal 320(7238): 846.
  5. Bruce MG, Rosenstein NE, Capparella JM, et al. 2001. Risk factors for meningococcal disease in college students. Journal of the American Medical Association 286(6): 688–93.
  6. Nelson SJ, Charlett A, Orr HJ, et al. 2001. Risk factors for meningococcal disease in university halls of residence. Epidemiology and Infection 126(2): 211–17.
  7. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  8. Baker M, McNicholas A, Garrett N, et al. 2000. Household crowding a major risk factor for epidemic meningococcal disease in Auckland children. Pediatric Infectious Diseases Journal 19(10): 983–90.
  9. Vesikari T, Esposito S, Prymula R, et al. 2013. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. The Lancet 381(9869): 825–35.
  10. Centers for Disease Control and Prevention. 2015. Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2015. Mortality and Morbidity Weekly Report 64(22): URL: http://www.cdc.gov/mmwr/pdf/wk/mm6422.pdf (accessed 25 August 2015).
  11. Centers for Disease Control and Prevention. 2015. Use of serogroup B meningococcal vaccines in adolescents and young adults: recommendations of the Advisory Committee on Immunization Practices, 2015. Morbidity and Mortality Weekly Report 64(41): 1171–6. URL: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6441a3.htm (accessed 1 December 2016).
  12. Public Health England. 2015. Immunisation Against Meningococcal B Disease for Infants Aged from Two Months: Information for Health Professionals. URL: https://www.gov.uk/government/publications/meningococcal-b-vaccine-information-for-healthcare-professionals (accessed 17 July 2015).
  13. Public Health England. 2016. Meningococcal. In: The Green Book. URL: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/554011/Green_Book_Chapter_22.pdf (accessed 1 December 2016).
  14. Campbell H, Borrow R, Salisbury D, et al. 2009. Meningococcal C conjugate vaccine: the experience in England and Wales. Vaccine 27(Suppl 2): B20–9.
  15. Maiden MCJ, Stuart JM, for the UK Carriage Group. 2002. Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination. The Lancet 359(9320): 1829–31.
  16. Ramsay ME, Andrews NJ, Trotter CL, et al. 2003. Herd immunity from meningococcal serogroup C conjugate vaccination in England: database analysis. British Medical Journal 326(7385): 365–6.
  17. Balmer P, Borrow R, Miller E. 2002. Impact of meningococcal C conjugate vaccine in the UK. Journal of Medical Microbiology 51(9): 717–22.
  18. MacNeil JR, Cohn AC, Zell ER, et al. 2011. Early estimate of the effectiveness of quadrivalent meningococcal conjugate vaccine. Pediatric Infectious Disease Journal 30(6): 451–5.
  19. Rennels M, King J, Ryall R, et al. 2004. Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants. Pediatric Infectious Disease Journal 23(5): 429–35.
  20. Hedari CP, Khinkarly RW, Dbaibo GS. 2014. Meningococcal serogroups A, C, W-135, and Y tetanus conjugate vaccine: a new conjugate vaccine against invasive meningococcal disease. Infection and Drug Resistance 7(3 April): 85–99. DOI: 10.2147/IDR.S36243 (accessed 25 August 2015).
  21. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  22. Arguedas A, Soley C, Loaiza C, et al. 2010. Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines. Vaccine 28(18): 3171–9.
  23. Gasparini R, Conversano M, Bona G, et al. 2010. Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults. Clinical and Vaccine Immunology 17(4): 537–44.
  24. Bryant KA, McVernon J, Marchant CD, et al. 2012. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Human Vaccines & Immunotherapeutics 8(8): 1036–41.
  25. Klein NP, Reisinger KS, Johnston W, et al. 2012. Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants. Pediatric Infectious Disease Journal 31(1): 64–71.
  26. Centers for Disease Control and Prevention. 2013. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports 62(2): 1–28. URL: www.cdc.gov/mmwr/pdf/rr/rr6202.pdf (accessed 27 September 2013).
  27. Pina LM, Bassily E, Machmer A, et al. 2012. Safety and immunogenicity of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants and toddlers: three multicenter phase III studies. Pediatric Infectious Disease Journal 31(11): 1173–83.
  28. Department of Health and Ageing. 2016. Meningococcal disease. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-10 (accessed 21 December 2016).
  29. Granoff DM, Pelton S, Harrison LH. 2013. Meningococcal vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  30. Conterno LO, da Silva Filho CR, Ruggeberg JU, et al. Conjugate vaccines for preventing meningococcal C meningitis and septicaemia (Review). Cochrane Database of Systematic Reviews 2006, Issue 3, Art. No. CD001834. DOI: 10.1002/14651858.CD001834.pub2 (accessed 20 August 2013).
  31. Centers for Disease Control and Prevention. 2013. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mortality and Morbidity Weekly Report Recommendations and Reports 62(RR 02): 1-28.
  32. Velentgas P, Amato AA, Bohn RL, et al. 2012. Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination. Pharmacoepidemiology and Drug Safety 21(12): 1350–8. DOI: 10.1002/pds.3321 (accessed 21 December 2016).
  33. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).
  34. Simmons G, Jones N, Calder L. 2000. Equivalence of ceftriaxone and rifampicin in eliminating naso-pharyngeal carriage of serogroup B N. meningitidis. Journal of Antimicrobial Chemotherapy 45(6): 909–11.
  35. Schaad UB, Salam MA, Aujard Y, et al. 1995. Use of fluoroquinolones in pediatrics: consensus report of an International Society of Chemotherapy Commission. Pediatric Infectious Disease Journal 14(1): 1–9.

13 Mumps

In this chapter:

Key information

13.1 Virology

13.2 Clinical features

13.3 Epidemiology

13.4 Vaccines

13.5 Recommended immunisation schedule

13.6 Contraindications and precautions

13.7 Expected responses and AEFIs

13.8 Public health measures

13.9 Variations from the vaccine data sheet

References

Key information

Mode of transmission Airborne droplets or by direct contact with saliva or urine from an infected person.
Incubation period About 16 to 18 days, ranging from 12 to 25 days.
Period of communicability From 7 days before the onset of parotitis until 9 days after the onset of illness.
Funded vaccine MMR vaccine (Priorix) is a live attenuated vaccine.
Dose, presentation, route

0.5 mL per dose after reconstitution.

Pre-filled syringe and glass vial. The vaccine must be reconstituted prior to injection.

Subcutaneous injection.

Funded vaccine indications and schedule

Children at ages 15 months and 4 years.

Adults who are susceptible to one or more of measles, mumps and rubella.

For (re-)vaccination following immunosuppression (if the individual is immunocompetent enough to safely receive the vaccine).

Vaccine efficacy/ effectiveness 64–66 percent effective against laboratory-confirmed mumps after 1 dose and 83–88 percent after 2 vaccine doses.
Egg allergy Egg allergy, including anaphylaxis, is not a contraindication for MMR vaccine.
Adverse events to vaccine MMR vaccine is generally well tolerated. The risk of adverse reactions to MMR vaccine is low, compared to the risk of complications from mumps disease.

13.1 Virology

Mumps is a paramyxovirus, genus Rubulavirus, with a single-stranded RNA genome. It is rapidly inactivated by heat, formalin, ether, chloroform and light.

13.2 Clinical features

Mumps is transmitted by airborne droplets or direct contact with infected respiratory tract secretions or urine. Humans are the only known host of the virus. The period of communicability ranges from seven days before the onset of parotitis until nine days after the onset of illness.

Classic mumps, an acute viral illness, is characterised by fever, headache, and swelling and tenderness of one or more parotid (salivary) glands. Patients may have no involvement of salivary glands but still experience involvement of other organs (eg, orchitis or meningitis). At least 30 percent of mumps infections in children are asymptomatic.

The complications of symptomatic mumps include aseptic meningitis in 15 percent (almost always without sequelae), orchitis (usually unilateral) in up to 20 percent of post-pubertal males, and oophoritis in 5 percent of post-pubertal females. Sterility occurs rarely. Profound unilateral nerve deafness occurs in 1 in 15,000 cases. Encephalitis has been reported to occur at a frequency of between 1 in 400 and 1 in 6,000, the latter being a more realistic estimate. Pancreatitis, neuritis, arthritis, mastitis, nephritis, thyroiditis and pericarditis may also occur.

The case fatality rate for mumps encephalitis is 1.4 percent, while the overall mumps case fatality rate is reported as 1.8 per 10,000 cases. Mumps in the first trimester of pregnancy may increase the rate of spontaneous abortion, but there is no evidence that it causes fetal abnormalities.

13.3 Epidemiology

13.3.1 Global burden of disease

Prior to the introduction of immunisation, approximately 85 percent of adults had evidence of past mumps infection. Most infections in those aged under 2 years were subclinical, while those affected in adulthood are more likely to experience severe disease. The peak incidence was in late winter and spring.

More recently, there have been numerous reports of increasing numbers of mumps cases in the US, UK and elsewhere, thought to be due to a waning of vaccine-induced immunity.1 Many cases are reported in 18‍‍–‍30 year olds.2 Outbreaks appear to occur mainly in those in crowded situations such as university students.3

13.3.2 New Zealand epidemiology

Mumps vaccine (as MMR) was introduced to the Schedule in 1990 for children aged 12 to 15 months, with a second dose introduced in 1992 for children aged 11 years. The current two-dose schedule at ages 15 months and 4 years was introduced in 2001 (see Appendix 1 for more information). The last mumps epidemic occurred in 1994.

In 2016, 20 cases of mumps were notified (16 were laboratory confirmed), compared to 13 notifications in 2015 (6 were laboratory confirmed). The 2016 mumps notification rate was 0.4 per 100,000 population, similar to the 2015 rate (0.3 per 100,000) (ESR, 14 March 2017).

From 1 September 2016 to 7 March 2017, 45 confirmed and probable cases of mumps have been notified to EpiSurv (provisional data). This is higher than observed for the same period in previous years: 2015/16 (6 cases), 2014/15 (10 cases) and 2013/2014 (10 cases).

13.4 Vaccines

13.4.1 Available vaccines

Mumps vaccine is one of the components of the live attenuated MMR and MMRV vaccines, considered in sections 11.4 and 21.4. Single antigen mumps vaccine is not available in New Zealand.

Funded vaccine
Other vaccines

MMR II (MSD) was the funded vaccine prior to the 1 July 2017 Schedule change (see section 11.4.1).

13.4.2 Efficacy and effectiveness

A 2012 Cochrane review of the safety and effectiveness of MMR vaccine estimated that a single dose of MMR vaccine was 69–81 percent effective in preventing clinical mumps. Effectiveness of MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64 and 66 percent for one dose and between 83 and 88 percent for two vaccine doses.4

A two-dose vaccination schedule and high immunisation coverage has been very successful in controlling disease. However, outbreaks can still occur in highly immunised populations because two doses of vaccine are not 100 percent effective. Declining vaccine-induced mumps immunity may also contribute to outbreaks.1 Data from Finland shows that 20 years after the second MMR dose, immunity to rubella was secure, 95 percent of people remained sero-positive for measles and immunity to mumps declined, with 74 percent being sero-positive.5 The antibody avidity also decreased over time, by 8 percent for measles and 24 percent for mumps.6

A third dose of MMR vaccine has been used safely and effectively during mumps outbreaks in highly immunised populations.7 Although the mumps vaccine is less effective than measles and rubella vaccines, cases that have been vaccinated are significantly less likely to experience complications from disease such as orchitis, meningitis and hospitalisation.8

13.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.9 Store at +2°C to +8°C. Do not freeze.

MMR vaccine must be reconstituted only with the diluents supplied by the manufacturer. Use MMR vaccine as soon as possible after reconstitution. If storage is necessary, reconstituted MMR vaccine can be stored at +2°C to +8°C for up to eight hours.

13.4.4 Dosage and administration

The dose of MMR is all of the reconstituted vaccine (approximately 0.5 mL) administered by subcutaneous injection (see section 2.2.3).

Co-administration with other vaccines

MMR vaccine can be given concurrently with other vaccines, as long as separate syringes are used and the injections are given at different sites. If not given concurrently, live vaccines should be given at least four weeks apart. (See also section 2.2.7 for information about multiple injections at the same visit.)

Interchangeability

The two brands of MMR vaccine (Priorix and MMR II) may be used interchangeably for completion of a course.10

13.5 Recommended immunisation schedule

Table 13.1: Recommended MMR vaccine schedule
  Schedule
Usual childhood schedulea 2 doses: at ages 15 months and 4 years
Catch-upb for children, adolescents and adults 2 doses: at least 4 weeks apart
  1. If MMR is given to children aged 6–12 months for outbreak control, 2 further MMR doses are still required at ages 15 months and 4 years.
  2. MMR vaccine is funded for those who are susceptible to 1 or more of the 3 diseases.

13.5.1 Usual childhood schedule

Two doses of mumps vaccine as MMR are recommended at age 15 months and age 4 years (Table 13.1).

The second dose can be given as soon as four weeks after the first dose.

Children who in an outbreak receive MMR vaccine when aged under 12 months require two further doses administered after age 12 months. The first scheduled MMR vaccine may be given to children from age 12 months whose parents/guardians request it, and no opportunity should be missed to achieve immunity.

13.5.2 Catch-up

MMR is recommended and funded for children, adolescents and adults who are known to be susceptible to one or more of the three diseases (two doses, four weeks apart). See sections 11.5.2 and 18.5.2.

13.5.3 Immunocompromise

In general, MMR is contraindicated in immunocompromised individuals (see section 4.3). They can be partially protected from exposure to infection by ensuring that all contacts are fully immunised, including hospital staff and family members. There is no risk of transmission of MMR vaccine viruses from a vaccinee to the immunocompromised individual. See section 11.7.2.

MMR vaccine is funded for (re-)vaccination following immunosuppression. However, it is important to be sure that the individual is immunocompetent enough to safely receive the vaccine.

HIV infection

Discuss vaccination of individuals with HIV infection with their specialist (see ‘HIV infection’ in section 4.3.3).

MMR vaccine is recommended for all HIV-positive children, whether symptomatic or asymptomatic, if the CD4+ lymphocyte percentage is 15 percent or greater. Asymptomatic children who are not severely immunocompromised are recommended to receive MMR vaccine from age 12 months to provide early protection against the three diseases. Susceptible HIV-positive children and adults aged 14 years and older may receive MMR vaccine if the CD4+ lymphocyte count is 200 cells/mm3 or greater. Administration of MMR with CD4+ counts below these recommended levels has been associated with vaccine-related pneumonitis (from the measles component).11

13.5.4 Pregnancy and breastfeeding

MMR vaccine is contraindicated during pregnancy. Pregnancy should be avoided for four weeks after MMR vaccination.11, 12

MMR vaccine can be given to breastfeeding women.

13.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general vaccine contraindications.

13.6.1 Contraindications

See section 11.6.1 for specific MMR vaccine contraindications.

Anaphylaxis to a previous dose of MMR or any of the vaccine components (including neomycin) is a contraindication to a further dose of MMR.

MMR vaccine should not be given to women who are pregnant, and pregnancy should be avoided for four weeks after immunisation.11, 12

13.6.2 Precautions

Egg allergy, including anaphylaxis, is not a contraindication to MMR vaccine. See section 11.6.3 for more information, and section 11.6.2 for further precautions.

13.7 Expected responses and AEFIs

See sections 11.7 and 18.7.

13.8 Public health measures

13.8.1 Diagnosis

All suspected mumps cases should have diagnostic testing (by buccal swab) as there are other causes of parotitis other than the mumps virus. See the ‘Mumps’ chapter of the Communicable Disease Control Manual 201213 for the specimens required for laboratory confirmation of mumps, or discuss these with the local laboratory.

13.8.2 Susceptible contacts

A susceptible contact is anyone born after 1981 who has not had mumps infection or has not been fully vaccinated for their age and who has had close contact with the case during the period of communicability (from 7 days before the onset of parotitis until 9 days after the onset of illness).

All susceptible contacts should be offered MMR vaccine. The mumps vaccine given after exposure has not been shown to be effective in preventing infection, but immunisation will provide protection against future exposure. There is no increased risk of adverse events after immunisation during the incubation period of mumps or if the recipient is already immune. Immunoglobulin is ineffective after exposure to mumps.

13.8.3 Exclusion

Cases

Exclude cases from school, early childhood services or health care work and from close contact with other susceptible people for 5 days from onset of glandular swelling.13 Previously immunised (pre-exposure) contacts need not be excluded.

Susceptible contacts

Discuss exclusion of susceptible contacts with the local medical officer of health. Generally, unimmunised contacts who have no previous history of mumps infection should be advised not to attend early childhood services or school because of:

Consider advising exclusion of susceptible contacts from school, early childhood services or work for 25 days after last exposure to the infectious case, if there are other susceptible people present.13

If a susceptible contact is vaccinated following exposure, they still need to be excluded (for the current outbreak) for 25 days. The vaccine given after exposure has not been shown to be effective in preventing infection, but immunisation will provide protection against future exposure. Contacts immunised prior to exposure do not need to be excluded.

For more details on control measures, refer to the ‘Mumps’ chapter of the Communicable Disease Control Manual 2012.13

13.9 Variations from the vaccine data sheet

See section 11.9 for variations from the MMR (Priorix) data sheet.

References

  1. Albertson JP, Clegg WE, Reid HD, et al. 2016. Mumps outbreak at a university and recommendation for a third dose of Measles-Mumps-Rubella vaccine — Illinois, 2015–2016. Morbidity and Mortality Weekly Report 65(29): 731–4. URL: https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6529a2.pdf (accessed 20 October 2016).
  2. Public Health England. 2017. Laboratory-confirmed cases of measles, mumps and rubella, England: October to December 2016. Infection Report 11(8): 1–5. URL: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/594801/hpr0817__mmr.pdf (accessed 11 March 2017).
  3. Centers for Disease Control and Prevention. 2017. Mumps Cases and Outbreaks. https://www.cdc.gov/mumps/outbreaks.html (accessed 24 March 2017).
  4. Demicheli V, Rivetti A, Debalini MG, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database of Systematic Reviews 2012, Issue 2, Art. No. CD004407. DOI: 10.1002/14651858.CD004407.pub3 (accessed 27 August 2013).
  5. Davidkin I, Jokinen S, Broman M, et al. 2008. Persistence of measles, mumps and rubella antibodies in an MMR vaccinated cohort: a 20-year follow-up. Journal of Infectious Diseases 197(7): 950–6.
  6. Kontio M, Jokinen S, Paunio M, et al. 2012. Waning antibody levels and avidity: implications for MMR vaccine-induced protection. Journal of Infectious Diseases 206(10): 1542–8.
  7. Ogbuanu IU, Kutty PK, Hudson JM, et al. 2012. Impact of a third dose of measles-mumps-rubella vaccine on a mumps outbreak. Pediatrics 130(6): e1567–74. DOI: 10.1542/peds.2012-0177 (accessed 8 January 2013).
  8. Hahné S, Whelan J, van Binnendijk R, et al. 2012. Mumps vaccine effectiveness against orchitis. Emerging Infectious Diseases 18(1): 191–3.
  9. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  10. Department of Health and Ageing. 2016. Measles. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-9 (accessed 20 October 2016).
  11. American Academy of Pediatrics. 2015. Measles. In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  12. Strebel PM, Papania MJ, Fiebelkorn AP, et al. 2013. Measles vaccine. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  13. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).

14 Pertussis (whooping cough)

In this chapter:

Key information

14.1 Bacteriology

14.2 Clinical features

14.3 Epidemiology

14.4 Vaccines

14.5 Recommended immunisation schedule

14.6 Contraindications and precautions

14.7 Expected responses and AEFIs

14.8 Public health measures

14.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission By aerosolised droplets.
Incubation period 7–10 days (range 5–21 days).
Period of communicability For control purposes, the communicable stage lasts from the catarrhal stage to 3 weeks after the onset of paroxysmal cough in a case not treated with antimicrobials. When treated with an effective antibiotic (eg, erythromycin), infectivity lasts until 5 days of antibiotics have been taken.
At-risk populations Infants aged under 12 months, particularly those too young to be immunised.
Funded vaccines

DTaP-IPV-HepB/Hib (Infanrix-hexa).

DTaP-IPV (Infanrix-IPV).

Tdap (Boostrix).

Dose, presentation, route

0.5 mL per dose.

DTaP-IPV-HepB/Hib: pre-filled syringe and glass vial. The vaccine must be reconstituted prior to injection.

DTaP-IPV, Tdap: pre-filled syringe.

Intramuscular injection.

Funded vaccine indications and schedule

Usual childhood schedule:

  • at age 6 weeks, 3 months and 5 months: DTaP‑IPV‑HepB/Hib
  • at age 4 years: DTaP-IPV
  • at age 11 years: Tdap

During pregnancy (from 28 to 38 weeks’ gestation): Tdap.

For (re-)vaccination of eligible patients: DTaP‑IPV‑HepB/Hib, DTaP-IPV or Tdap.

Dose interval between Td and Tdap No minimum interval is required between Td and Tdap, unless Tdap is being given as part of a primary immunisation course.
Vaccine efficacy/ effectiveness 84 percent efficacy after the 3-dose primary course in infants, lasting up to age 6 years. Immunity (whether from natural infection or immunisation) wanes over time.
Precautions Children with an evolving neurological disorder.
Adverse events from vaccine Thigh or upper arm swelling occurs in 2–3 percent of children after the fourth and fifth doses.

14.1 Bacteriology

Pertussis (whooping cough) is a bacterial respiratory infection caused by Bordetella pertussis, a gram-negative bacillus. The bacillus is fastidious (it requires special media to culture), and will often have cleared or decreased in numbers by the time the typical cough develops, making laboratory confirmation by culture difficult. The development of sensitive and specific PCR and serological assays has improved our ability to demonstrate B. pertussis infection (see section 14.8).

14.2 Clinical features

Pertussis is highly transmissible and it is one of the most infectious vaccine-preventable diseases. The expected number of secondary cases caused by an infectious individual with pertussis (R₀) is approximately 14, similar to measles, and several-fold greater than influenza1 (see section 1.2.1). Transmission occurs by aerosolised droplets, and the incubation period is 7 to 10 days (range 5 to 21 days).

The initial catarrhal stage, during which infectivity is greatest, is of insidious onset with rhinorrhoea and an irritating cough that can progress to severe paroxysms of coughing. In the catarrhal stage, which usually lasts one to two weeks, the only clue to diagnosis may be contact with a known case. This stage is followed by the paroxysmal stage, with coughing episodes characterised by a series of short expiratory bursts, followed by an inspiratory gasp or typical whoop, and/or vomiting. Patients appear relatively well between paroxysms and are usually afebrile.

Clinical presentation varies with age, immunisation status and previous infection. In young infants apnoea and/or cyanosis may precede paroxysmal cough, and it is important they are recognised as presenting symptoms of severe disease. Thus pertussis must be considered in infants presenting with an acute life-threatening event, or apnoea.2 In school-aged children immunised in infancy, symptoms that distinguish pertussis from other causes of coughing illnesses are inspiratory whoop, post-tussive vomiting and the absence of wheezing and fever.3

Almost all pertussis infections in adolescents and adults occur in the context of previous infection and/or immunisation. Persistent cough, sometimes for more than four weeks, is the cardinal feature in adults.4 Cough is worse at night and often paroxysmal, the patient waking with a choking sensation. Post-tussive vomiting and whoop are infrequent. A scratchy throat and sweating attacks are common.

Studies performed in several countries during both epidemic and non-epidemic periods have shown that between 12 and 37 percent of school-aged children, adolescents and adults with persistent cough (lasting 14 days or more) have evidence of recent B. pertussis infection.3, 4, 5, 6, 7, 8, 9 A primary care-based study in New Zealand performed during the early phase of the 2011 to 2013 epidemic showed recent B. pertussis infection in 17 percent of children aged 5–16 years and 7 percent of adults aged 17–49 years presenting to primary care with a persistent cough of two or more weeks’ duration.10

The most common complications of pertussis are secondary infections, such as otitis media and pneumonia, and the physical sequelae of paroxysmal coughing (eg, subconjunctival haemorrhages, petechiae, epistaxes, central nervous system haemorrhages, pneumothoraces and herniae). At the peak of the paroxysmal phase, vomiting can lead to weight loss, especially in infants and young children. The disease is most often severe in infants in the first few months of life. Of infants with pertussis sufficiently severe to require intensive care admission, one in six will either die or be left with brain or lung damage.11

14.3 Epidemiology

The epidemiology of B. pertussis infection and pertussis disease differ. Infection occurs across the age spectrum, and repeated infection without disease is common.12 The endemic circulation of B. pertussis in older children and adults provides a reservoir for spread of the infection and the development of severe disease in incompletely vaccinated infants.

14.3.1 Global burden of disease

Pertussis mortality rates have always been highest in the first year of life.13, 14 In the US during the 1940s pertussis resulted in more infant deaths than measles, diphtheria, poliomyelitis and scarlet fever combined.13 Beyond age 3 years mortality rates have always been relatively low. In immunised populations virtually all deaths occur in the first two months of life, and deaths in toddlers and preschool-aged children have largely disappeared. Among infants, younger age, lack of immunisation, low socioeconomic status, premature gestation, low birthweight and female gender are associated with an increased risk of fatal pertussis.14

Pertussis mortality and morbidity15 is under-reported. It is estimated that in high-income countries three times more deaths are due to pertussis than are reported.15, 16, 17, 18 Infants continue to die from pertussis despite state-of-the-art intensive care.11, 19, 20, 21, 22

Since the introduction of mass immunisation, countries with consistently high immunisation coverage rates achieve consistently low pertussis incidence rates.23, 24 Higher pertussis incidence rates are due primarily to lower immunisation coverage, but also in some instances to lower vaccine efficacy or less-than-optimal immunisation schedules.25, 26, 27, 28, 29

The decrease in incidence following the introduction of mass immunisation has been most pronounced in those aged under 10 years. Despite this, the reported pertussis disease rates have remained highest in infants and young children.30, 31, 32 Infants aged under 3 months have the highest rate of notification and hospitalisation.33, 34

Pertussis is an epidemic disease with two- to five-yearly epidemic cycles. Epidemics are frequently sustained over 18 months or more, during which there are dramatic increases in hospital admission rates. Pertussis does not show the seasonal variability that is typical of most respiratory infections.

The epidemic periodicity of pertussis has not lengthened with the introduction of mass immunisation, unlike other epidemic diseases for which mass immunisation is used, such as measles. This lack of lengthening of the pertussis epidemic cycle implies minimal impact of mass immunisation on the circulation of B. pertussis in the human population.12, 35, 36

14.3.2 New Zealand epidemiology

Pertussis mortality in New Zealand

On average, there are zero to one deaths from pertussis each year in New Zealand. During the most recent pertussis epidemic (see below) there were three deaths in children: two in infants aged under 6 weeks and one in an unimmunised preschooler. There were no deaths from pertussis (as recorded in EpiSurv) in 2014 or 2015.37

Pertussis morbidity in New Zealand

Pertussis morbidity in New Zealand has usually been described using hospital discharge data. National passive surveillance data has been available since 1996, when pertussis became a notifiable disease.

Pertussis morbidity in New Zealand as described by notification data

In 2015, 1,168 cases were notified, of which 650 were laboratory-confirmed.37 The 2015 notification rate was 25.4 per 100,000 population, similar to the rate in 2014 (24.4 per 100,000, 1,099 cases). Infants had the highest notification rate (152.3 per 100,000, 90 cases), followed by children aged 1–4 years (55.1 per 100,000, 136 cases). By ethnicity, Pacific peoples had the highest notification rate (31.8 per 100,000, 90 cases), followed by European/Other (26.2 per 100,000, 800 cases) and Māori (25.7 per 100,000, 176 cases).

Three epidemics have occurred since pertussis became a notifiable disease, with an epidemic peak annual number of notified cases of 4,140 in 2000, 3,485 in 2004, and 5,897 in 2012 (see Figure 14.1).37

Figure 14.1: Pertussis notifications and hospitalisations, 1998–2015
Figure 14.1: Pertussis notifications and hospitalisations, 1998–2015

Note: Includes confirmed, probable and suspect cases, and notifications still under investigation.

Source: ESR

Since pertussis became notifiable, the annual proportion of notified cases aged 30 years or older has increased from 23 percent (in 1997) to 44 percent in 2015.37 However, the highest proportion of hospitalised cases continues to be in infants. From 2010 to 2015 there were 1,075 notified cases in infants. Hospitalisation status was recorded for 977 of the infant cases; of these, 527 (54 percent) were hospitalised (Figure 14.2).

Figure 14.2: Age distribution of notified and hospitalised pertussis cases, 2010–2015 cumulative data
Figure 14.2: Age distribution of notified and hospitalised pertussis cases, 2010–2015 cumulative data

Source: ESR

Pertussis morbidity in New Zealand, as described by hospital discharge data

Hospitalisation rates for pertussis, as measured by ICD discharge diagnostic codes, provide a measure of severe pertussis disease. The discharge rate in the 2000s was lower than in the 1990s (2000s versus 1990s, relative risk 0.79 [95% CI: 0.74–0.84]). Despite this decrease, the infant hospitalisation rate for pertussis in New Zealand in the 2000s (196 per 100,000) remained three times higher than contemporary rates in Australia (2001 infant rate: 56 per 100,000) and the US (2003 infant rate: 65 per 100,000).38, 39, 40

Pertussis hospital admission rates vary with ethnicity and household deprivation. From 2006 to 2010 the infant (aged under 12 months) pertussis hospital discharge rate (per 1,000) was higher for Māori (1.49; relative risk 2.29 [95% CI: 1.77–2.96]) and Pacific peoples (2.03; relative risk 3.11 [95% CI: 2.30–4.22]) and lower for Asian/Indian (0.31; relative risk 0.47 [95% CI: 0.25–0.90]) compared with European/Other people (0.65 per 1,000).41

From 2006 to 2010 an infant living in a household in the most deprived quintile was at a four-fold increased risk of being hospitalised with pertussis compared with an infant in the least deprived quintile (1.89 versus 0.39 per 1,000; relative risk 4.81 [95% CI: 2.99–7.75]).41

14.4 Vaccines

Whole-cell pertussis vaccine for routine use was introduced in 1960 and was replaced with acellular pertussis vaccine in 2000. The current schedule of three acellular pertussis-containing vaccines in the first year of life plus booster doses at ages 4 and 11 years has been in effect since 2006. See Appendix 1 for more information about the history of pertussis-containing vaccines in New Zealand.

14.4.1 Available vaccines

Funded pertussis vaccines
Other vaccines

Other acellular pertussis-containing vaccines registered (approved for use) and available (marketed) in New Zealand include:

14.4.2 Efficacy and effectiveness

Immunogenicity

A review of published data on DTaP-IPV-HepB/Hib found it to be highly immunogenic in infants aged under 2 years for primary and booster vaccination.42 In clinical studies there was a strong immune response against the vaccine antigens, which persisted for up to approximately six years after vaccination. A review of published clinical trial and post-marketing surveillance data supported the immunogenicity of DTaP‑IPV-HepB/Hib across a range of schedules and when administered concurrently with other vaccines.43

Efficacy and effectiveness

The acellular pertussis vaccines approved for use in New Zealand have been shown to provide around 81–85 percent efficacy (95% CI: 51–100) after three infant doses, with follow-up studies suggesting sustained efficacy to age 6 years.44, 45, 46

Observational study data suggests that acellular pertussis vaccines, while effective, may be less effective than the best performing whole-cell vaccines in preventing whooping cough.47, 48 Children and adolescents who have received acellular pertussis vaccine for their entire pertussis immunisation series are at greater risk of pertussis than children whose immunisation series included some doses of whole-cell vaccine and some doses of acellular vaccine.49

See section 4.1.2 for information about maternal pertussis vaccine effectiveness and safety.

Duration of protection

Protection against pertussis begins to wane within several years of completion of a three-dose primary and two-dose booster dose immunisation series. The US has a pertussis immunisation schedule that includes three doses of acellular vaccine during infancy and booster doses at 15 to 18 months and 4 to 6 years.50 The risk of pertussis increases in the six years after receipt of the fifth dose of this series, indicating a waning in vaccine-induced immunity over this time interval.

In adults, a trial of a monovalent acellular pertussis vaccine in the US among people aged 15–65 years found an efficacy of 92 percent (95% CI: 32–99) after a median of 22 months of follow-up.51 Antibodies to pertussis toxoid, filamentous hemagglutinin and pertactin have been shown to persist five years after receipt of Tdap (Boostrix) in a study of Australian adults aged 18 years and older.52 However, the duration of protection is unknown.

14.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.53 Store at +2°C to +8°C. Do not freeze.

DTaP-IPV-HepB/Hib should be stored in the dark.

14.4.4 Dosage and administration

The dose of DTaP-IPV-HepB/Hib, DTaP-IPV and Tdap is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

Co-administration with other vaccines

DTaP-IPV-HepB/Hib, DTaP-IPV and Tdap can be administered simultaneously (at separate sites) with other vaccines or IGs.

14.5 Recommended immunisation schedule

Table 14.1: Immunisation schedule for pertussis-containing vaccines (excluding catch-up)
Age Vaccine Comment
6 weeks DTaP-IPV-HepB/Hib Primary series
3 months DTaP-IPV-HepB/Hib Primary series
5 months DTaP-IPV-HepB/Hib Primary series
4 years DTaP-IPV Booster
11 years Tdap Booster
Pregnant women (weeks 28–38 of each pregnancy) Tdap Booster

14.5.1 Children

A primary course of pertussis vaccine is given as DTaP-IPV-HepB/Hib (Infanrix-hexa) at ages 6 weeks, 3 months and 5 months, followed by a dose of DTaP-IPV (Infanrix-IPV) at age 4 years (Table 14.1). A further booster is given at age 11 years (school year 7) as Tdap (Boostrix).

Dose intervals

The minimum interval between doses is four weeks, and the first dose should not be given before four weeks of age. If a course of immunisation is interrupted for any reason it may be resumed without repeating prior doses (see Appendix 2). A booster dose should be given no earlier than six months after the primary series.

Catch-up immunisation

See Appendix 2 for detailed catch-up immunisation information.

Dose interval between Td and Tdap

When Tdap is to be given to adolescents or adults to protect infants or other vulnerable individuals from pertussis, no minimum interval is required between Td and Tdap,54, 55, 56 – unless Tdap is being given as part of a primary immunisation course.

14.5.2 Pregnancy and breastfeeding

Pregnant women should receive a dose of Tdap (funded) from 28 to 38 weeks’ gestation. This should be given during each pregnancy57 to protect the mother and so that antibodies can pass to the fetus; post-partum maternal vaccination will reduce the risk of a mother infecting her baby but does not have the added benefit of providing passive antibodies.

See section 4.1.2 for information about maternal pertussis vaccine effectiveness and safety.

Tdap vaccines can be given to breastfeeding women.58

14.5.3 (Re-)vaccination

Pertussis-containing vaccines are funded for (re-)vaccination of eligible patients, as follows. See also sections 4.2 and 4.3.

DTaP-IPV-HepB/Hib (Infanrix-hexa) and DTaP-IPV (Infanrix-IPV)

An additional four doses (as appropriate) of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for (re‑)vaccination of patients:

Up to five doses of DTaP-IPV-HepB/Hib (for children aged under 10 years) or DTaP-IPV are funded for children requiring solid organ transplantation.

Tdap (Boostrix)

An additional four doses (as appropriate) of Tdap (Boostrix) are funded for patients:

14.5.4 Recommended but not funded

Tdap is recommended but not funded for:

14.6 Contraindications and precautions

See also section 2.1.3 for pre-vaccination screening guidelines and section 2.1.4 for general contraindications for all vaccines.

14.6.1 Contraindications

The only contraindication is an immediate severe anaphylactic reaction to the vaccine, or any component of the vaccine, following a previous dose.

14.6.2 Precautions

For children with an undiagnosed or evolving neurological disorder (eg, uncontrolled epilepsy or deteriorating neurological state), there is the potential for confusion about the role of vaccination in the context of a clinically unstable illness. The risks and benefits of withholding vaccination until the clinical situation has stabilised should be considered on an individual basis.

14.7 Expected responses and AEFIs

Unless the specific contraindications and precautions outlined in section 14.6 above are present, practitioners should have no hesitation in advising the administration of acellular pertussis vaccine. Although whole-cell pertussis vaccine has been associated with febrile seizures, there was never any good-quality evidence that it caused any more significant neurological disorder. Disorders for which any causal association with pertussis vaccine have been disproved include infantile spasms, Reye syndrome and SUDI.59, 60, 61, 62, 63, 64, 65, 66 Similar to previous studies, the New Zealand Cot Death Study found a lower rate of SUDI in immunised children.67 Acellular pertussis vaccine has been used in New Zealand since 2000 and is significantly less reactogenic than was the whole-cell pertussis vaccine.

14.7.1 DTaP-containing vaccines

DTaP-containing vaccines (eg, DTaP-IPV-HepB/Hib and DTaP-IPV) are generally well tolerated in children,68 including preterm (24 to 36 weeks’ gestation) and/or low birthweight (820–2,020 grams) infants.69, 70

Local reactions commonly include pain, redness, swelling and induration at the injection site.68 Less common reactions include fretfulness, anorexia, vomiting, crying, and slight to moderate fever.68 These local and systemic reactions usually occur within several hours of pertussis immunisation and spontaneously resolve within 48 hours without sequelae.68

Local reactions increase with age and additional doses of vaccine. The reaction may be due to some of the other vaccine components, such as aluminium. These reactions are usually minor and only last a day or so. In a small percentage of vaccine recipients the reactions will be severe enough to limit movement of the arm and may last for about a week.

14.7.2 Tdap vaccine

The adult reduced-concentration Td and Tdap (Boostrix) vaccines have been found to have no safety concerns in those aged 10–64 years and those aged over 65 years.71, 72, 73 Administration of Tdap to pregnant women did not identify any concerning patterns in maternal, infant, or fetal outcomes.74, 75

Local reactions following immunisation of adolescents with Tdap are common, but are usually mild. They include pain (in 75 percent of recipients), swelling (21 percent) and redness (23 percent) at the injection site.76

Expected systemic reactions following immunisation of adolescents with Tdap include fever >38°C (5 percent), headache (16 percent), fatigue (14 percent) and gastrointestinal symptoms (10 percent).76

14.7.3 Major adverse events associated with pertussis-containing vaccines

The incidence of major adverse events following primary pertussis immunisation is summarised in Table 14.2.

Table 14.2: Incidence (per 100,000 doses) of major adverse reactions following acellular pertussis vaccine
Event following immunisation Timing
post-vaccination
Incidence per 100,000 doses
Persistent (>3 hours) inconsolable screaming 0–24 hours 44
Seizures 0–2 days 7
Hypotonic-hyporesponsive episode 0–24 hours 0–47
in trials of acellular vaccines
Anaphylaxis 0–1 hour Very rare

Source: Edwards KM, Decker MD. 2008. Pertussis vaccine. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (5th edition). Philadelphia, PA: WB Saunders Company. Table 21.15.

Swelling involving the entire thigh or upper arm occurs in 2–3 percent of children after administration of the fourth and fifth doses of acellular pertussis vaccine.68 The pathogenesis is unknown. Resolution occurs without sequelae. Extensive limb swelling after the fourth dose does not predict an increased risk of a similar reaction following the fifth dose of pertussis vaccine and is not a contraindication to receipt of the fifth dose.

Neither a hypotonic-hyporesponsive episode nor seizures are associated with long-term consequences for the child77, 78, 79 (see section 2.3.3). Children who have febrile seizures after pertussis immunisation do not have an increased risk of subsequent seizures or neurodevelopmental disability.80 It is safe to give acellular pertussis vaccine after a hypotonic-hyporesponsive episode has occurred following a previous dose.81

14.8 Public health measures

14.8.1 Improving pertussis control

The goal of the pertussis immunisation programme is to protect those most at risk of developing severe disease; that is, infants in the first year of life. Two key strategies for reducing the burden of disease in infants are the administration of Tdap vaccination during pregnancy and on-time infant immunisation. Vaccination during pregnancy is recommended and funded for women from 28 to 38 weeks’ gestation (see section 14.5.2). More complete and timely delivery of the current infant immunisation schedule would reduce the infant pertussis disease burden.82 It is important that all children attending early childhood services should be fully vaccinated for their age.

In October 2012 the UK introduced a pertussis vaccination programme for pregnant women in response to a nationwide pertussis outbreak. The vaccine effectiveness for preventing laboratory-confirmed pertussis in infants aged under 3 months was estimated to be 91 percent (95% CI: 84–95).83 This high vaccine effectiveness is likely to be a result of protection of infants by both passive antibody transfer and reduced exposure to maternal disease.83

Data on the protective effects of indirect strategies is currently incomplete. Infants can be protected by immunisation of others at risk of developing pertussis, with whom the infant may come into contact.84 The ‘cocoon strategy’ is the term used to describe the protection of infants by immunising those who are potential sources of B. pertussis.84 This involves the targeted immunisation of adult groups who have the most contact with young and vulnerable infants. Three identified groups are (1) new mothers who have not had recent immunisation, family, and close contacts of newborns; (2) health care workers; and (3) early childhood workers.

Health care workers in particular are at increased risk of pertussis and can transmit pertussis to other health care workers and to patients.85 Outbreaks in maternity wards, neonatal units and outpatient settings have been described.86 Fatalities occur as a result of such nosocomial spread.87

Immunisation cannot be used to control a community outbreak, although action to update age-appropriate vaccination in institutional settings (schools and early childhood services) is appropriate. When an outbreak occurs, individual immunisation status should be checked and immunisation completed. In an outbreak setting, infants as young as four weeks of age can commence immunisation.

14.8.2 Notification

A suspected pertussis case can be confirmed if a clinically compatible illness is laboratory confirmed, or is epidemiologically linked to a confirmed case. Because transmission is by aerosolised droplets, health care personnel looking after pertussis cases should wear a mask even if vaccinated.

14.8.3 Laboratory diagnosis of Bordetella pertussis infection

PCR is the most sensitive method for diagnosing B. pertussis infection. In general, B. pertussis can be identified by PCR from most upper respiratory tract samples, including throat swabs, for up to four to six weeks after symptom onset. Serology may be useful when symptoms have been present for more than two weeks, at a time when PCR and culture are more likely to be negative.

The local laboratory should be consulted for the specifics of which swabs and transport media to use.

14.8.4 Antimicrobial treatment of case

A number of antibiotics are available for the treatment and prophylaxis of pertussis. Macrolide antibiotics can be used to reduce the severity and duration of clinical disease but only if started during the catarrhal phase. Antibiotics commenced after coughing paroxysms have begun have no effect on the clinical disease but do reduce the risk of spread of disease to others.68, 88, 89 Antibiotics are of limited value if started after 21 days of illness, but should be considered for high-risk contacts (eg, young infants and pregnant women). To minimise transmission to newborn infants, it is recommended that pregnant women diagnosed with pertussis in the third trimester be treated with appropriate antibiotics (see Table 14.3), even if six to eight weeks have elapsed since the onset of cough.90

Macrolide use during pregnancy, lactation and in the neonatal period is associated with an increased risk of infantile pyloric stenosis.91, 92 With erythromycin, the risk increases with decreasing age and increased duration of treatment.93 The risk is presumed to be lower with azithromycin, although there are case reports of infantile pyloric stenosis occurring when azithromycin has been used during pregnancy.

Parents should be informed of the risks of this complication and of the symptoms and signs of infantile hypertrophic pyloric stenosis. The infant should be monitored for this complication for four weeks after completion of treatment.68, 94, 95

Table 14.3: Recommended antimicrobial therapy and post-exposure prophylaxis for pertussis in infants, children, adolescents and adults
Age Recommended Alternative
Azithromycina Erythromycin Clarithromycinb TMP-SMXc
Younger than 4 weeks

Day 1: 10 mg/kg/day in a single daily dose

Days 2–5: 5 mg/kg/day in a single daily dose

40 mg/kg/day in 4 divided doses for 14 days Not recommended Contraindicated under age 2 months (risk for kernicterus)
1–5 months

Day 1: 10 mg/kg/day in a single daily dose

Days 2–5: 5 mg/kg/day in a single daily dose

40 mg/kg/day in 4 divided doses for 14 days 15 mg/kg per day in 2 divided doses for 7 days Aged 2 months or older: TMP, 8 mg/kg/day; SMX, 40 mg/kg/ day in 2 divided doses for 14 days
6 months or older and children

Day 1: 10 mg/kg/day in a single daily dose (maximum 500 mg)

Days 2–5: 5 mg/kg/ day in a single daily dose (max 250 mg per day)

40 mg/kg/day in 4 divided doses for 14 days (maximum 2 g/day) 15 mg/kg/day in 2 divided doses for 7 days (maximum 1 g/day) Aged 2 months or older: TMP, 8 mg/kg/day; SMX, 40 mg/kg/ day in 2 divided doses for 14 days
Adolescents and adults

Day 1: 500 mg as a single dose

Days 2–5:
250 mg once daily

2 g/day in 4 divided doses for 14 days 1 g/day in 2 divided doses for 7 days TMP, 320 mg/ day; SMX, 1,600 mg/day in 2 divided doses for 14 days
  1. Preferred macrolide during pregnancy, lactation and in infants <1 month old because of risk of idiopathic hypertrophic pyloric stenosis associated with erythromycin.
  2. Not funded for treatment or post-exposure prophylaxis in New Zealand.
  3. TMP = trimethoprim; SMX = sulfamethoxazole. TMP-SMX can be used as an alternative agent to macrolides in patients aged ≥2 months who are allergic to macrolides, who cannot tolerate macrolides, or who are infected with a rare macrolide-resistant strain of Bordetella pertussis.

Adapted from: Centers for Disease Control and Prevention. 2005. Recommended antimicrobial agents for treatment and post exposure prophylaxis of pertussis. Morbidity and Mortality Weekly Report 54(RR14): 1–16.

Cases should be excluded from early childhood services, school, or community gatherings until:

Children who have culture-proven pertussis should complete their immunisation series with all of the scheduled doses recommended for their age.

14.8.5 Management of contacts

The local medical officer of health will advise on the management of contacts. For more details on control measures, refer to the ‘Pertussis’ chapter of the Communicable Disease Control Manual 2012.96

A contact can be defined as someone who has been in close proximity (within one metre)97 of the index case for one hour or more during the case’s infectious period. Contacts include household members, those who have stayed overnight in the same room, and those who have had face-to-face contact with the case.96

Those most at risk from pertussis and who are therefore high-priority contacts for public health follow-up are:

The evidence for the effectiveness of chemoprophylaxis of contacts is limited. Antibiotics are currently only recommended for high-priority contacts as listed above and if given within three weeks of initial exposure to an infectious case.

Health care workers are frequently exposed to B. pertussis. Although the greatest priority is given to protecting young infants and unimmunised children, there are well-documented examples of spread from staff to older adult patients. Pertussis in adults can be debilitating and can cause significant morbidity in those with respiratory disease.

Chemoprophylaxis may therefore be useful for adults exposed to a health care worker with pertussis, and infection control or public health services should normally be involved. Factors to be considered when discussing chemoprophylaxis include whether adult pertussis vaccine has been administered within the last five years, the health status of the individual who has been exposed, how recent the exposure was, and the nature of the health care or special community setting.

Where a case worked in a maternity ward or newborn nursery for more than an hour while infectious, then all babies in that ward and their parents/carers who were exposed to the case (within one metre for more than one hour) should receive antibiotics. Note: If the minimum duration of exposure is uncertain, a neonate exposed to an infectious case for less than one hour may warrant being considered a close contact and receive antibiotics.98

Any contacts, high priority or otherwise, should be advised to avoid attending early childhood services, school, work or community gatherings if they become symptomatic. Additional restrictions may be advised by the local medical officer of health, in particular if there is significant risk of transmission of infection to high-priority individuals.

14.9 Variations from the vaccine data sheets

The DTaP-IPV-HepB/Hib (Infanrix-hexa) and DTaP-IPV (Infanrix-IPV) data sheets state that these vaccines are indicated for primary immunisation of infants and as a booster dose for children. The Ministry of Health recommends that DTaP-IPV-HepB/Hib and DTaP-IPV vaccines may also be used for catch-up of the primary schedule in children aged under 10 years (see Appendix 2).

The data sheets for DTaP-IPV-HepB/Hib, DTaP-IPV and Tdap (Boostrix) state that these vaccines are contraindicated in children with encephalopathy of unknown aetiology or with neurologic complications occurring within seven days following a vaccine dose. The Ministry of Health recommends instead that the only contraindication is a history of anaphylaxis to a previous dose or to any of the vaccine components (see section 14.6.1). The risks and benefits of withholding vaccination until the clinical situation has stabilised should be considered on an individual basis (see section 14.6.2).

Tdap is not approved for use (registered) for primary immunisation. However, the Ministry of Health recommends that children aged 7 to under 18 years may receive Tdap (funded) and adults aged over 18 years may receive Tdap (unfunded) for catch-up of the primary schedule (see Appendix 2).

The Tdap data sheet states that the vaccine may be used during pregnancy when the possible advantages outweigh the possible risks for the fetus. However, the Ministry of Health recommends and funds Tdap vaccine for all pregnant women from 28 to 38 weeks’ gestation (see section 14.5.2).

References

  1. Cowling BJ, Lau MS, Ho LM, et al. 2010. The effective reproduction number of pandemic influenza: prospective estimation. Epidemiology 21(6): 842–6.
  2. McGovern MC, Smith MB. 2004. Causes of apparent life threatening events in infants: a systematic review. Archives of Disease in Childhood 89(11): 1043–8.
  3. Harnden A, Grant C, Harrison T, et al. 2006. Whooping cough in school age children with persistent cough: prospective cohort study in primary care. British Medical Journal 333(7560): 174–7.
  4. Wirsing von Konig CH, Halperin S, Riffelmann M, et al. 2002. Pertussis of adults and infants. The Lancet Infectious Diseases 2(12): 744–50.
  5. Robertson PW, Goldberg H, Jarvie BH, et al. 1987. Bordetella pertussis infection: a cause of persistent cough in adults. Medical Journal of Australia 146(10): 522–5.
  6. Wirsing von Konig CH, Postels Multani S, Bock HL, et al. 1995. Pertussis in adults: frequency of transmission after household exposure. The Lancet 346(8986): 1326–9.
  7. Senzilet LD, Halperin SA, Spika JS, et al. 2001. Pertussis is a frequent cause of prolonged cough illness in adults and adolescents. Clinical Infectious Diseases 32(12): 191–7.
  8. Gilberg S, Njamkepo E, Du Chatelet IP, et al. 2002. Evidence of Bordetella pertussis infection in adults presenting with persistent cough in a French area with very high whole-cell vaccine coverage. Journal of Infectious Diseases 186(3): 415–18.
  9. Schmitt-Grohe S, Cherry JD, Heininger U, et al. 1995. Pertussis in German adults. Clinical Infectious Diseases 21(4): 860–6.
  10. Philipson K, Goodyear-Smith F, Grant C, et al. 2013. When is acute persistent cough in school-age children and adults whooping cough? British Journal of General Practice 63(613): e573-9. DOI: 10.3399/bjgp13X670705 (accessed 21 October 2013).
  11. J. Surridge, E. Segedin and C. Grant. 2007. Pertussis requiring intensive care. Archives of Disease in Childhood 92(11): 970–5.
  12. Cherry JD. 2005. The epidemiology of pertussis: a comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection. Pediatrics 115(5): 1422–7.
  13. Gordon JE, Aycock WL. 1951. Whooping cough and its epidemiological anomalies. American Journal of Medical Sciences 222(3): 333–61.
  14. Haberling DL, Holman RC, Paddock CD, et al. 2009. Infant and maternal risk factors for pertussis-related infant mortality in the United States, 1999 to 2004. Pediatric Infectious Disease Journal 28(3): 194–8.
  15. Sutter RW, Cochi SL. 1992. Pertussis hospitalizations and mortality in the United States, 1985–1988: evaluation of the completeness of national reporting. Journal of the American Medical Association 267(3): 386–91.
  16. Van Buynder PG, Owen D, Vurdien JE, et al. 1999. Bordetella pertussis surveillance in England and Wales: 1995–7. Epidemiology & Infection 123(3): 403–11.
  17. Crowcroft NS, Andrews N, Rooney C, et al. 2002. Deaths from pertussis are underestimated in England. Archives of Disease in Childhood 86(5):
    336–8.
  18. Shaikh R, Guris D, Strebel PM, et al. 1998. Underreporting of pertussis deaths in the United States: need for improved surveillance. Pediatrics 101(2): 323.
  19. Wortis N, Strebel PM, Wharton M, et al. 1996. Pertussis deaths: report of 23 cases in the United States, 1992 and 1993. Pediatrics 97(5): 607–12.
  20. Williams GD, Matthews NT, Choong RK, et al. 1998. Infant pertussis deaths in New South Wales 1996–1997. Medical Journal of Australia 168(6): 281–3.
  21. Halasa NB, Barr FE, Johnson JE, et al. 2003. Fatal pulmonary hypertension associated with pertussis in infants: does extracorporeal membrane oxygenation have a role? Pediatrics 112(6 Pt1): 1274–8.
  22. Mikelova LK, Halperin SA, Scheifele D, et al. 2003. Predictors of death in infants hospitalized with pertussis: a case-control study of 16 pertussis deaths in Canada. Journal of Pediatrics 143(5): 576–81.
  23. Joo I. 1991. Epidemiology of pertussis in Hungary. Developments in Biological Standardization 73: 357–9.
  24. Finger H, Wirsing von Konig CH, Tacken A, et al. 1991. The epidemiological situation of pertussis in the Federal Republic of Germany. Developments in Biological Standardization 73: 343–55.
  25. Miller E, Vurdien JE, White JM. 1992. The epidemiology of pertussis in England and Wales. Communicable Disease Report: CDR Review 2(13): R152–4.
  26. White JM, Fairley CK, Owen D, et al. 1996. The effect of an accelerated immunisation schedule on pertussis in England and Wales. Communicable Disease Report: CDR Review 6(6): R86–91.
  27. Romanus V, Jonsell R, Bergquist SO. 1987. Pertussis in Sweden after the cessation of general immunization in 1979. Pediatric Infectious Disease Journal 6(4): 365–71.
  28. Noble GR, Bernier RH, Esber EC, et al. 1987. Acellular and whole-cell pertussis vaccines in Japan: report of a visit by US scientists. Journal of the American Medical Association 257(10): 1351–6.
  29. Kimura M, Kuno-Sakai H. 1990. Developments in pertussis immunisation in Japan. The Lancet 336(8706): 30–2.
  30. Provenzano RW, Wetterlow LH, Sullivan CL. 1959. Pertussis immunization in pediatric practice and in public health. New England Journal of Medicine 261(10): 473–8.
  31. Farizo KM, Cochi SL, Zell ER, et al. 1992. Epidemiological features of pertussis in the United States, 1980–1989. Clinical Infectious Diseases 14(3): 708–19.
  32. Guris D, Strebel PM, Bardenheier B, et al. 1999. Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990–1996. Clinical Infectious Diseases 28(6): 1230–7.
  33. Ranganathan S, Tasker R, Booy R, et al. 1999. Pertussis is increasing in unimmunised infants: is a change in policy needed? Archives of Disease in Childhood 80(3): 297–9.
  34. Tanaka M, Vitek CR, Pascual FB, et al. 2003. Trends in pertussis among infants in the United States, 1980–1999. Journal of the American Medical Association 90(22): 2968–75.
  35. Crowcroft NS, Pebody RG. 2006. Recent developments in pertussis. The Lancet 367(9526): 1926–36.
  36. Broutin H, Guegan JF, Elguero E, et al. 2005. Large-scale comparative analysis of pertussis population dynamics: periodicity, synchrony, and impact of vaccination. American Journal of Epidemiology 161(12):
    1159–67.
  37. Institute of Environmental Science and Research Ltd. 2016. Notifiable Diseases in New Zealand: Annual Report 2015. URL: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2015/2015AnnualReportFinal.pdf (accessed 16 November 2016).
  38. Grant CC. 2012. Recent indication of progress in pertussis hospitalisation rates in NZ. Australian and New Zealand Journal of Public Health 36(4): 398.
  39. Elliott E, McIntyre P, Ridley G, et al. 2004. National study of infants hospitalized with pertussis in the acellular vaccine era. Pediatric Infectious Disease Journal 23(3): 246–52.
  40. Cortese MM, Baughman AL, Zhang R, et al. 2008. Pertussis hospitalizations among infants in the United States, 1993 to 2004. Pediatrics 121(3): 484–92.
  41. Craig E, Adams J, Oben G, et al. 2013. The Health Status of Children and Young People in New Zealand. URL: http://dnmeds.otago.ac.nz/departments/womens/paediatrics/research/nzcyes/pdf/Rpt2011_NZReport.pdf (accessed 21 July 2013).
  42. Dhillon S. 2010. DTPa-HBV-IPV/Hib vaccine (Infanrix hexa): a review of its use as primary and booster vaccination. Drugs 70(8): 1021–58.
  43. Zepp F, Schmitt HJ, Cleerbout J, et al. 2009. Review of 8 years of experience with Infanrix hexa (DTPa-HBV-IPV/Hib hexavalent vaccine). Expert Review of Drugs 8(6): 663–78.
  44. Greco D, Salmaso S, Mastrantonio P, et al. 1996. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. New England Journal of Medicine 334(6): 341–8.
  45. Edwards KM, Decker MD. 2013. Pertussis vaccines. In: Plotkin SA, Orenstein W, Offit PA (eds). Vaccines (6th edition). Philadelphia, PA: Elsevier Saunders.
  46. Gustafsson L, Hessel L, Storsaeter J, et al. 2006. Long-term follow up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates need for a booster dose at 5 to 7 years of age. Pediatrics 118(3): 978–84. DOI: 10.1542/peds.2005-2746 (accessed 15 December 2013).
  47. Sheridan SL, Ware RS, Grimwood K, et al. 2012. Number and order of whole cell pertussis vaccines in infancy and disease protection. Journal of the American Medical Association 308(5): 454–6. DOI: 10.1001/jama.2012.6364 (accessed 12 December 2016).
  48. Sheridan SL, Ware RS, Grimwood K, et al. 2015. Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not confounded by age or receipt of booster-doses. Vaccine 33(39): 5027–30. URL: http://dx.doi.org/10.1016/j.vaccine.2015.08.021 (accessed 12 December 2016).
  49. Witt MA, Arias L, Katz PH, et al. 2013. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clinical Infectious Diseases 56(9): 1248–54.
  50. Tartof SY, Lewis M, Kenyon C, et al. 2013. Waning immunity to pertussis following 5 doses of DTaP. Pediatrics 131(4): e1407–52. DOI: 10.1542/peds.2012-1928 (accessed 21 July 2013).
  51. Ward JI, Cherry JD, Chang SJ, et al. 2005. Efficacy of an acellular pertussis vaccine among adolescents and adults. New England Journal of Medicine 353(15): 1555–63.
  52. McIntyre P, Burgess MA, Egan A, et al. 2009. Booster vaccination of adults with reduced-antigen-content diphtheria, tetanus and pertussis vaccine: immunogenicity 5 years post-vaccination. Vaccine 27(7): 1062–6.
  53. Ministry of Health. 2017. National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017. URL: www.health.govt.nz/coldchain (accessed 14 February 2017).
  54. Beytout J, Launay O, Guiso N, et al. 2009. Safety of Tdap-IPV given 1 month after Td-IPV booster in healthy young adults: a placebo controlled trial. Human Vaccines and Immunotherapeutics 5(5): 315–21.
  55. Talbot EA, Brown KH, Kirkland KB, et al. 2010. The safety of immunizing with tetanus-diphtheria-acellular pertussis vaccine (Tdap) less than 2 years following previous tetanus vaccination: experience during a mass vaccination campaign of health care personnel during a respiratory illness outbreak. Vaccine 28(50): 8001–7.
  56. Centers for Disease Control and Prevention. 2011. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. Morbidity and Mortality Weekly Report 60(1): 13–15. URL: www.cdc.gov/mmwr/pdf/wk/mm6001.pdf (accessed 21 October 2013).
  57. Centers for Disease Control and Prevention. 2013. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women – Advisory Committee on Immunization Practices (ACIP), 2012. Morbidity and Mortality Weekly Report 62(7): 131–5. URL: www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a4.htm (accessed 22 October 2013).
  58. Department of Health and Ageing. 2016. Pertussis. In: The Australian Immunisation Handbook (10th edition; updated August 2016). URL: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-19 (accessed 27 November 2016).
  59. Howson CP, Fineberg HV. 1992. Adverse events following pertussis and rubella vaccines: summary of a report of the Institute of Medicine. Journal of the American Medical Association 267(3): 392–6.
  60. Walker AM, Jick H, Perera DR, et al. 1988. Neurologic events following diphtheria-tetanus-pertussis immunization. Pediatrics 81(3): 345–9.
  61. Griffin MR, Ray WA, Mortimer EA, et al. 1990. Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine. Journal of the American Medical Association 263(12): 1641–5.
  62. Melchior JC. 1977. Infantile spasms and early immunization against whooping cough: Danish survey from 1970 to 1975. Archives of Disease in Childhood 52(2): 134–7.
  63. Shields WD, Nielsen C, Buch D, et al. 1988. Relationship of pertussis immunization to the onset of neurologic disorders: a retrospective epidemiologic study. Journal of Pediatrics 113(5): 801–5.
  64. Taylor EM, Emery JL. 1982. Immunization and cot deaths. The Lancet 320(8300): 721.
  65. Hoffman HJ, Hunter JC, Damus K, et al. 1987. Diphtheria-tetanus-pertussis immunization and sudden infant death: results of the National Institute of Child Health and Human Development Cooperative Epidemiological Study of Sudden Infant Death Syndrome risk factors. Pediatrics 79(4): 598–611.
  66. Flahault A, Messiah A, Jougla E, et al. 1988. Sudden infant death syndrome and diphtheria/tetanus toxoid/pertussis/poliomyelitis immunisation. The Lancet 331(8585): 582–3.
  67. Mitchell EA, Stewart AW, Clements M. 1995. Immunisation and the sudden infant death syndrome: New Zealand Cot Death Study Group. Archives of Disease in Childhood 73(6): 498–501.
  68. American Academy of Pediatrics. 2015. Pertussis (whooping cough). In: Kimberlin DW, Brady MT, Jackson MA, et al (eds). Red Book: 2015 Report of the Committee on Infectious Diseases (30th edition). Elk Grove Village, IL: American Academy of Pediatrics.
  69. Lyseng-Williamson KA, Dhillon S. 2012. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM): a guide to its use in infants. Pediatric Drugs 14(5):
    337–43.
  70. Omeñaca F, Garcia-Sicilia J, García-Corbeira P, et al. 2005. Response of preterm newborns to immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio and Haemophilus influenzae type b vaccine: first experiences and solutions to a serious and sensitive issue. Pediatrics 116(6): 1292–98.
  71. Jackson LA, Yu O, Belongia EA, et al. 2009. Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study. BMC Infectious Diseases 9(165): e1–7. DOI: 10.1186/1471-2334-9-165 (accessed 31 January 2013).
  72. Yih WK, Nordin JD, Kulldorff M, et al. 2009. An assessment of the safety of adolescent and adult tetanus-diphtheria-acellular pertussis (Tdap) vaccine, using active surveillance for adverse events in the Vaccine Safety Datalink. Vaccine 27(32): 4257–62.
  73. Moro PL, Yue X, Lewis P, et al. 2011. Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005–2010. Vaccine 29(50): 9404–8.
  74. Zheteyeva YA, Moro PL, Tepper NK, et al. 2012. Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women. American Journal of Obstetrics and Gynecology 207(1): 59.e1–7.
  75. Donegan K, King B, Bryan P. 2014. Safety of pertussis vaccination in pregnant women in the UK: observational study. British Medical Journal 349(11 July): g4219. DOI: 10.1136/bmj.g4219 (accessed 10 August 2014).
  76. Centers for Disease Control and Prevention. 2006. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report 55(RR-3): 1–44. URL: www.cdc.gov/mmwr/pdf/rr/rr5503.pdf (accessed 21 October 2013).
  77. Baraff LJ, Shields WD, Beckwith L, et al. 1988. Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation. Pediatrics 81(6): 789–94.
  78. Braun MM, Terracciano G, Salive ME, et al. 1998. Report of a US public health service workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization. Pediatrics 102(5): E52.
  79. Hirtz DG, Nelson KB, Ellenberg JH. 1983. Seizures following childhood immunizations. Journal of Pediatrics 102(1): 14–18.
  80. Barlow WE, Davis RL, Glasser JW, et al. 2001. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. New England Journal of Medicine 345(9): 656–61.
  81. Goodwin H, Nash M, Gold M, et al. 1999. Vaccination of children following a previous hypotonic-hyporesponsive episode. Journal of Paediatrics and Child Health 35(6): 549–52.
  82. Grant CC, Roberts M, Scragg R, et al. 2003. Delayed immunisation and risk of pertussis in infants: unmatched case-control study. British Medical Journal 326(7394): 852–3. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153471/pdf/852.pdf (accessed 21 October 2013).
  83. Amirthalingam G, Andrews N, Campbell H, et al. 2014. Effectiveness of maternal pertussis vaccination in England: an observational study. The Lancet 384(9953): 1521–8. DOI: http://dx.doi.org/10.1016/S0140-6736(14)60686-3 (accessed 10 August 2015).
  84. McIntyre P, Wood N. 2009. Pertussis in early infancy: disease burden and preventive strategies. Current Opinion in Infectious Diseases 22(3):
    215–23.
  85. de Serres G, Shadmani R, Duval B, et al. 2000. Morbidity of pertussis in adolescents and adults. Journal of Infectious Diseases 182(1): 174–9.
  86. Centers for Disease Control and Prevention. 2008. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report: Recommendations and Reports 57(RR-4): 1–51. URL: www.cdc.gov/mmwr/PDF/rr/rr5704.pdf (accessed 21 October 2013).
  87. Bonacorsi S, Farnoux C, Bidet P, et al. 2006. Treatment failure of nosocomial pertussis infection in a very-low-birth-weight neonate. Journal of Clinical Microbiology 44(10): 3830–2.
  88. Wirsing von Konig CH. 2005. Use of antibiotics in the prevention and treatment of pertussis. Pediatric Infectious Disease Journal 24(5 Suppl): S66–68.
  89. Bergquist SO, Bernander S, Dahnsjo H, et al. 1987. Erythromycin in the treatment of pertussis: a study of bacteriologic and clinical effects. [Erratum appears in Pediatric Infectious Disease Journal 1987; 6(11): 1035.] Pediatric Infectious Disease Journal 6(5): 458–61.
  90. Centers for Disease Control and Prevention. 2000. Guidelines for the Control of Pertussis Outbreaks. URL: www.cdc.gov/pertussis/outbreaks/guide/downloads/chapter-05.pdf (accessed 21 October 2013).
  91. Cooper WO, Ray WA, Griffin MR. 2002. Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstetrics & Gynecology 100(1): 101–6.
  92. Sorensen HT, Skriver MV, Pedersen L, et al. 2003. Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides. Scandinavian Journal of Infectious Diseases 35(2): 104–6.
  93. Maheshwai N. 2007. Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis? Archives of Disease in Childhood 92(3): 271–3.
  94. Centers for Disease Control and Prevention. 1999. Hypertrophic pyloric stenosis in infants following pertussis prophylaxis with erythromycin–Knoxville, Tennessee, 1999. Morbidity and Mortality Weekly Report 48(49): 1117–20. URL: www.cdc.gov/mmwr/PDF/wk/mm4849.pdf (accessed 21 October 2013).
  95. Honein MA, Paulozzi LJ, Himelright IM, et al. 1999. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. [Erratum appears in The Lancet 2000; 355(9205): 758.] The Lancet 354(9196): 2101–5.
  96. Ministry of Health. 2012. Communicable Disease Control Manual 2012. URL: http://www.health.govt.nz/publication/communicable-disease-control-manual-2012 (accessed 15 November 2016).
  97. Centers for Disease Control and Prevention. 2005. Recommended antimicrobial agents for treatment and postexposure prophylaxis of pertussis. Morbidity and Mortality Weekly Report: Recommendations and Reports 54(RR-14): 1–16. URL: www.cdc.gov/mmwr/pdf/rr/rr5414.pdf (accessed 11 November 2013).
  98. Communicable Diseases Network Australia. 2015. Pertussis: CNDA National Guidelines for Public Health Units. URL: http://www.health.gov.au/internet/main/publishing.nsf/content/3240888A0EA7E16BCA257BF000191641/$File/pertussis-3.0-april2015.pdf (accessed 14 February 2017).

15 Pneumococcal disease

In this chapter:

Key information

15.1 Bacteriology

15.2 Clinical features

15.3 Epidemiology

15.4 Vaccines

15.5 Recommended immunisation schedule

15.6 Contraindications and precautions

15.7 Expected responses and AEFIs

15.8 Public health measures

15.9 Variations from the vaccine data sheets

References

Key information

Mode of transmission Contact with respiratory droplets.
Incubation period Asymptomatic nasopharyngeal carriage is common. The incubation period is variable and may be as short as
1–3 days.
Burden of disease Particularly the young, the elderly and the immunocompromised.
Funded vaccines

All children aged under 5 years: PCV10 (Synflorix).

Children and adults with eligible conditions:

  • PCV13 (Prevenar 13)
  • 23PPV (Pneumovax 23).
Dose, presentation and route

All vaccines:

  • 0.5 mL per dose
  • pre-filled syringe
  • intramuscular injection (23PPV may also be given subcutaneously).
Funded vaccine indications and schedule

PCV10 at ages 6 weeks, 3, 5 and 15 months, or age-appropriate catch-up. Children who started with PCV13 can continue with PCV10.

PCV13 and 23PPV age-appropriate schedules for
(re-)vaccination of children and adults with eligible conditions.

PCV13 and 23PPV for testing for primary immune deficiencies.

Vaccine efficacy/ effectiveness For pneumococcal conjugate vaccines: reductions in pneumococcal disease and carriage of vaccine serotypes in vaccinated populations, plus herd immunity effects reducing pneumococcal disease in other age groups; some increases in disease caused by non-vaccine serotypes.
Precautions

There may be an increased risk of fever and febrile convulsions with concomitant PCV13 and influenza vaccine in children aged 6 months to under 5 years.

23PPV should not be given to children aged under 2 years due to the reduced immune response associated with polysaccharide vaccines.

15.1 Bacteriology

Streptococcus pneumoniae is a gram-positive diplococcus. It is ubiquitous, and many individuals carry the organism asymptomatically in their upper respiratory tract.1 There are over 90 identifiable serotypes of S. pneumoniae. Certain serotypes are more invasive or more associated with antibiotic resistance, and dominant serotypes vary by age and geographical distribution.

Table 15.1 summarises the serotypes contained in the pneumococcal conjugate (PCV) and polysaccharide (PPV) vaccines.

Table 15.1: Summary of pneumococcal vaccine serotype content
Vaccine Serotypes
PCV7 Serotypes 4, 6B, 9V, 14, 18C, 19F, 23F
PCV10*

Includes:

  • the serotypes contained in PCV7
  • plus serotypes 1, 5, 7F.
PCV13

Includes:

  • the serotypes contained in PCV10
  • plus serotypes 3, 6A, 19A.
23PPV

Includes:

  • the serotypes contained in PCV13 (except for 6A)
  • plus serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F.

*     PCV10 contains serotype 19F, which elicits cross-reactive antibodies against serotype 19A.2

15.2 Clinical features

The human nasopharynx is the only natural reservoir of S. pneumoniae. Carriage rates in young children range up to 75 percent.3 Transmission of S. pneumoniae is by contact with respiratory droplets, and although nasopharyngeal colonisation precedes disease, most who are colonised do not develop invasive disease. The nasopharynx is a source of spread between individuals, and reduction of S. pneumoniae vaccine serotypes in children by vaccination results in less transmission to, and disease in, adults. Invasive pneumococcal disease (IPD) is the severe end of the pneumococcal disease spectrum and includes cases in which S. pneumoniae has been isolated from a usually sterile site (such as blood, pleural fluid or cerebrospinal fluid). Major clinical syndromes are bacteraemic pneumonia, bacteraemia without a focus and meningitis; older adults most commonly have bacteraemic pneumonia while young children may have any of the three, with meningitis being the most severe.

Mucosal or non-invasive infection is extremely common, such as acute otitis media (the most common childhood bacterial infection), and sinusitis and pneumonia (without bacteraemia) in all age groups. The incubation period of S. pneumoniae infection is variable but may be as short as one to three days.

15.3 Epidemiology

15.3.1 Global burden of disease

Pneumococcal diseases are a common cause of morbidity and mortality worldwide, though rates of disease and death are higher in low-income countries than in high-income countries, with the majority of deaths occurring in sub-Saharan Africa and Asia.4 Along with the very old and very young, patients with underlying conditions have the highest rates of disease.

The WHO estimates that 476,000 (range 333,000–529,000) children aged under 5 years died from pneumococcal infections in 2008.4 Five percent of all-cause child mortality in 2008 was due to pneumococcal infections.

Global epidemiology since the introduction of PCV
Herd immunity

There is good evidence for the indirect (herd) effects of infant PCV immunisation on pneumococcal disease due to vaccine serotypes in the non-vaccinated population, especially in adults aged 65 years and older. This includes data showing reductions in the rates of IPD due to PCV7 serotypes in non-vaccinated groups in the US (for both adult pneumonia and IPD in adults),5, 6, 7 England and Wales,8 the Netherlands,9 Norway10 and Denmark11 and New Zealand (see Figure 15.1). These herd effects are due to decreased nasopharyngeal carriage of vaccine types in immunised children resulting in reduced transmission to unimmunised older children and adults. Although most of New Zealand data demonstrates the indirect effect on vaccine-type IPD (see Figure 15.2), there is also evidence of an all-age effect on non-bacteraemic pneumonia.12 Data from Norway13 and Canada14 indicates further decreases in vaccine-type IPD in non-vaccinated populations (aged 5 years and older) after PCV13 replaced PCV7 on the infant immunisation schedule.

Impact of vaccination on non-invasive pneumococcal disease

The impact of pneumococcal conjugate vaccination on the large burden of non-invasive pneumococcal disease has been clearly demonstrated internationally in countries that have introduced these vaccines, particularly through reductions in childhood hospitalisations due to pneumonia.15, 16 Other impacts, such as on acute otitis media, are less clear and more difficult to measure accurately.17

15.3.2 New Zealand epidemiology

Pneumococcal disease occurs throughout the year, but is more common in the autumn and winter months.18, 19 Historically, the risk of disease is highest in infants and the elderly,20, 21 especially Māori and Pacific peoples.18, 20, 22 The introduction of PCV has substantially reduced the risk of IPD in vaccinated infants (see below).

Invasive isolates from cases of IPD are serogrouped and serotyped at ESR. Detailed surveillance information can be found on the ESR Public Health Surveillance website (www.surv.esr.cri.nz/surveillance/IPD.php).

Incidence and mortality

There were 447 IPD cases notified in 2015 (ESR, 1 February 2017). The notification rate was 9.7 cases per 100,000 population, a decrease from 2014 (10.8 cases per 100,000 population; 489 cases) and significantly lower than the 2009 peak rate of 16.2 per 100,000 population (697 cases).

Adults aged 85 years and older (53.7 per 100,000), 75–84 years (35.4 per 100,000), 65–74 years (25.8 per 100,000) and children aged under 1 year (16.9 per 100,000) had the highest rates of IPD (ESR, 1 February 2017). The age-standardised rates of IPD were highest for the Pacific peoples (31.3 per 100,000, 51 cases) and Māori (27.7 per 100,000, 107 cases) ethnic groups. The rates for these ethnic groups were, respectively, 4.3 and 3.8 times higher than the rate for the European/Other ethnic group (7.3 per 100,000, 259 cases).

IPD was recorded as the primary cause of death for 27 cases in 2015 (ESR, 1 February 2017). There were no deaths due to IPD in children aged under 5 years.

In 2015, the most commonly reported risk factor in cases aged under 5 years was premature birth (50.0 percent), and for cases aged 5 years and older it was having a chronic illness (55.2 percent).23

New Zealand epidemiology since the introduction of PCV

PCV7 was introduced in June 2008, PCV10 in July 2011 and PCV13 in July 2014. From 1 July 2017, PCV10 will again be used on the routine Schedule (see Appendix 1 for the history of pneumococcal vaccination in New Zealand).

IPD incidence

There have been dramatic reductions in the incidence of IPD in the vaccine-eligible age groups in New Zealand since the introduction of PCV to the Schedule in 2008 (see Figure 15.1).

In New Zealand children aged under 2 years, the rate of IPD has decreased by 88 percent since the introduction of PCV to the Schedule: from an average annual rate of 100.3 per 100,000 for 2006/0724 to 11.8 per 100,000 in 2015.23 The impact on IPD caused by PCV7 serotypes in this age group is even greater (see Figure 15.2), with only one case of IPD in a child aged under 2 years due to a PCV7 serotype in 2015 (ESR, 1 February 2017).

Similar reductions were seen for IPD caused by PCV10 and PCV13 serotypes in children aged under 2 years (see Figure 15.2). The rate of IPD has also significantly decreased in children aged 2 to 4 years, for all-cause IPD (Figure 15.1) and IPD caused by PCV serotypes (Figure 15.2).

Figure 15.1: Rate per 100,000 of invasive pneumococcal disease by age group and year, 2006–2015

Notes:

PCV7 was introduced in 2008, PCV10 in 2011 and PCV13 in 2014.

IPD became a notifiable disease in 2008. Data presented from 2009 onwards is based on IPD notifications, and data prior to 2009 is from ESR’s national laboratory-based surveillance of IPD.

Source: ESR

Figure 15.2: Rate per 100,000 population of invasive pneumococcal disease due to PCV7 serotypes, additional PCV10 types, additional PCV13 types and non-PCV types, by age group and year, 2006–2015

Notes:

PCV7 was introduced in 2008, PCV10 in 2011 and PCV13 in 2014.

‘PCV7 serotypes’ are cases due to serotypes covered by PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F); ‘Serotypes 1, 5 and 7F’ are cases due to the additional serotypes contained in PCV10; ‘Serotypes 3, 6A and 19A’ are cases due to the additional serotypes contained in PCV13; and ‘Other serotypes’ are all other culture-positive IPD cases.

IPD became a notifiable disease in 2008. Data presented from 2009 onwards is based on IPD notifications, and data prior to 2009 is from ESR’s national laboratory-based surveillance of IPD.

Source: ESR

Pneumococcal serotypes

Of the 447 IPD cases notified in 2015, 430 were referred to ESR for serotyping (ESR, 1 February 2017). Just over 90 percent (22/24) of cases in children aged under 5 years were due to serotypes not covered by PCV10, compared with 71.7 percent (142/198) and 83.6 percent (174/208) of cases in the 5–64 years age group and 65 years and older age group, respectively.

Serotype 19A was the most common of all serotypes (90 cases) in 2015 (ESR, 1 February 2017). Three of these 19A cases were in children aged under 5 years (none of whom had received PCV13), down from 17 cases in this age group in 2014.

Serotype 22F was the most common non-vaccine serotype in 2015, although there was little change in cases of 22F disease between 2014 and 2015 (39 to 40 cases) (ESR, 1 February 2017).

Herd immunity

The addition of PCV to the New Zealand schedule in 2008 has seen significant reductions in IPD due to PCV serotypes in age groups not eligible for routine infant immunisation (Figure 15.2). Between 2006/07 and 2015 the rate of IPD due to all vaccine serotypes in the 65 years and older age group decreased 43 percent, from an average of 28.0 per 100,000 population in 2006/07 to 16.0 per 100,000 in 2015, while in the 5–64 years age group there was a 30 percent decrease over the same time period (5.0 to 3.5 per 100,000) (ESR, 1 February 2017). However the overall rate of IPD in these age groups has only marginally decreased due to non-vaccine serotype replacement disease.

Impact of vaccination on non-invasive pneumococcal disease

While hospitalisations for respiratory infections in children aged 5 years and under have been increasing in New Zealand, hospitalisations for all-cause pneumonia have declined significantly since the implementation of the pneumococcal conjugate vaccine programme in 2008. The largest reductions in all-cause pneumonia hospitalisations between 2006 and 2015 were in Māori (a 12 percent reduction) and Pacific children (a 21 percent reduction) and those living in areas of high deprivation.25 In children aged under 2 years living in Counties Manukau DHB, the introduction of PCV7 was associated with a 70 percent reduction in the risk of pneumonia hospitalisations in Pacific children but there was less impact (a 5 percent risk reduction) for Māori children.26

Antimicrobial resistance

As in other countries, there has been concern at the increase in the prevalence of antimicrobial resistance in S. pneumoniae in New Zealand. Introduction of pneumococcal conjugate vaccination has reduced the circulation of resistant pneumococcal serotypes elsewhere.27

In New Zealand, S. pneumoniae resistance to betalactams (penicillin and cefotaxime) has shown little change over the last 10 years; the 2015 rate of penicillin resistance (meningitis interpretation) of 21.9 percent was within the range of rates recorded for other years during the last decade (14.1–22.3 percent) (ESR, 1 February 2017). Similarly, the 2015 rate of cefotaxime resistance of 2.6 percent was within the range recorded for other years during the last decade (1.9–5.1 percent).

In 2015 PCV7 serotypes accounted for a smaller proportion (20.2 percent) of the penicillin-resistant isolates than previous years (92.8 percent in 2006/07), and type 19A accounted for a larger proportion (52.1 percent) (ESR, 1 February 2017). The prevalence of penicillin resistance among serotype 19A isolates has increased significantly in recent years from an average of 15.8 percent in 2006/07 to 54.4 percent in 2015.

15.4 Vaccines

15.4.1 Available vaccines

There are two types of pneumococcal vaccine registered (approved for use) and available (marketed) in New Zealand for use against S. pneumoniae: protein conjugate pneumococcal vaccine and unconjugated polysaccharide pneumococcal vaccine. In the protein conjugate vaccines, the pneumococcal surface polysaccharide is coupled to a carrier protein. The protein conjugate induces increased production of antibodies, immunological memory and maturation of the antibody response, enabling an effective immune response in children aged under 2 years (see section 1.4.3).

Funded vaccines

15.4.2 Efficacy and effectiveness

10-valent pneumococcal conjugate vaccine (PCV10)
IPD

Two key randomised controlled trials have demonstrated the protective efficacy and effectiveness of PCV10 against pneumococcal disease.2 The Finnish Invasive Pneumococcal disease (FinIP) study investigated a two- or three-dose infant series plus a toddler booster.28 Vaccine effectiveness against culture-confirmed vaccine-serotype IPD was shown to be 100 percent (95% CI: 83–100) following the 3+1 schedule and 92 percent (95% CI: 58–100) for the 2+1 schedule. Based on national hospital discharge register data, vaccine effectiveness was 71 percent (95% CI: 52–83) for patient file-verified non-laboratory-confirmed IPD.29

In the Clinical Otitis Media and Pneumonia Study (COMPAS) phase III trial in Latin America (Argentina, Colombia and Panama), approximately 24,000 infants received PCV10 or HepB at ages 2, 4 and 6 months with a booster at age 15–18 months.30 The study showed that the vaccine effectiveness of PCV10 was 100 percent (95% CI: 74.3–100) against pneumococcal vaccine-serotype IPD and 65 percent (95% CI: 11.1–86.2) against any IPD.

A matched case-control study conducted in Brazil found that, following the introduction of PCV10 (as a 3+1 schedule) in 2010, the adjusted effectiveness against vaccine-serotype IPD was 83.8 percent (95% CI: 65.9–92.3) for an age-appropriate PCV10 schedule.31 The study included 316 cases of IPD and 1,219 neighbourhood age-matched controls. Age-appropriate PCV10 immunisation was up-to-date for 94 (30 percent) cases and 521 (43 percent) of the controls.

Meningitis

A decrease in pneumococcal meningitis morbidity and mortality was observed two years after the introduction of routine PCV10 vaccinations in Brazil in children aged under 2 years, based on data obtained from the Information System on Notifiable Diseases from 2007 to 2012.32

Overall, the incidence of pneumococcal meningitis decreased by 50 percent from 3.7 per 100,000 population in 2007 to 1.84 per 100,000 in 2012.32 Mortality decreased by 69 percent from 1.3 per 100,000 to 0.4 per 100,000.

During the study period, there were 1,311 cases and 430 deaths attributed to laboratory-confirmed pneumococcal meningitis (serotypes not determined).32 The greatest impact of PCV10 vaccination was seen in the infants aged 6–11 months, with a 73 percent reduction in pneumococcal meningitis incidence (from 7.46 cases per 100,000 in 2007 to 2.02 cases per 100,000 in 2012) and an 85 percent reduction in mortality (from 3.25 deaths per 100,000 in 2007 to 0.49 deaths per 100,000 in 2012).

Pneumonia

The FinIP trial also provided data on the protective effectiveness of PCV10 against hospital-diagnosed pneumonia in Finland. Vaccine effectiveness against all pneumonia episodes was 25.2 percent (95% CI: 2.6–42.6) for the 3+1 PCV10 schedule and 27.6 percent (95% CI: 5.5–44.6) for the 2+1 schedule.2 A study in children aged under 4 years showed a significant decrease of 12.65 percent (p<0.001) in all pneumonia hospitalisations in Brazil when comparing the pre-vaccination (2002–2009) and post-PCV10 vaccination introduction periods (2011–2012).33 No reduction in non-respiratory-cause hospitalisations were observed for the same time period (p=0.39).

Further studies in Brazil have continued to show significant reductions in pneumonia in children aged under 2 years following the introduction of PCV10 to the infant schedule. Active population-based surveillance studies were conducted in Central Brazil (across 17 paediatric hospitals) to investigate pneumonia hospitalisations in children aged under 36 months before and after the introduction of PCV10.34 The relative rate reduction was 13.1 percent (95% CI: −13.4, −12.9) for clinical and 25.4 percent (95% CI: −26.0, −24.7) for x-ray-confirmed pneumonia in children aged 2–23 months.

Otitis media

A secondary outcome of the COMPAS trial in Latin America was to assess the vaccine effectiveness of PCV10 against clinically confirmed acute otitis media (AOM).30 At the end of the study, the intent-to-treat analysis found that vaccine effectiveness against AOM was 19.0 percent (95% CI: 4.4–31.4; p=0.007; n=254 vaccinated, 308 controls). When the cause of the AOM was investigated further, vaccine effectiveness was calculated as 55.7 percent (95% CI: 21.5–75.0; n=17 vaccinated, 38 controls) against pneumococcal AOM and 69.9 percent (29.8–87.1; n=7 vaccinated, 23 controls) against vaccine-serotypes. For NTHi confirmed-AOM, vaccine effectiveness was 21.5 percent (95% CI: −43.4, −57.0; n=19 vaccinated, 24 controls).

13-valent pneumococcal conjugate vaccine (PCV13)
Individuals at increased risk of IPD

Few studies have investigated the immunogenicity and effectiveness of PCV13 in individuals at increased risk of IPD. Studies using pneumococcal vaccines with similar but fewer antigens have demonstrated vaccine efficacy in individuals with immunocompromising conditions (eg, HIV, sickle cell disease), but the duration of protection against IPD remains unknown.35 High IgG titres have been observed following PCV13 vaccination of children with sickle cell disease,36 HIV infection37 and nephrotic syndrome.38

Oropharyngeal carriage may be a risk factor for IPD in children and adolescents with underlying medical conditions (eg, type 1 diabetes,39 cancer,40 cystic fibrosis,41 asthma42). The broader serotype protection provided by PCV13 may be of benefit for these children when oropharyngeal carriage is considered as a risk factor for pneumococcal disease, although booster doses may be necessary.39

Use of pneumococcal conjugate vaccines in adults

PCV13 induces robust immune responses in adults,43, 44, 45, 46 including elderly adults.47 The antibody titres vary with serotype and between age groups, particularly for those aged over 65 years.46 However, the clinical significance of this variation was not determined.

There is little data on the effectiveness of pneumococcal conjugate vaccines in adults. A large randomised controlled trial was conducted in the Netherlands to investigate the impact of PCV13 vaccination in reducing vaccine-serotype pneumococcal community-acquired pneumonia (CAP), non-bacteraemic and non-invasive pneumococcal CAP, and IPD in adults aged 65 years and older.48 PCV13 was effective in preventing vaccine-type pneumococcal CAP (vaccine efficacy 45.6 percent, 95% CI: 21.8–62.5), bacteraemic and non-bacteraemic CAP (vaccine efficacy 45 percent, 95% CI: 14.2–65.3) and vaccine-type IPD (vaccine efficacy 75 percent, 95% CI: 41.4–90.8).

PCV13 is at least as immunogenic as 23PPV in adults. Some studies suggest that 23PPV attenuates the immune response to subsequent doses of PCV13.47, 49, 50 This attenuation is not seen if PCV13 is given before 23PPV; PCV13 may augment the response to subsequent 23PPV vaccination.47, 49, 50

23-valent vaccine pneumococcal polysaccharide (23PPV)

The polysaccharide vaccine (23PPV, Pneumovax 23) is made from the purified capsular polysaccharide antigens of 23 serotypes of S. pneumoniae. It is available in New Zealand for adults and children from age 2 years. 23PPV includes the 23 serotypes (see Table 15.1) responsible for about 90 percent or more of cases of invasive disease in high-income countries.

23PPV efficacy

Assessment of the efficacy of pneumococcal vaccination depends on whether immune-competent or immunocompromised patients are studied, and whether the end point is pneumococcal pneumonia or bacteraemia.

The problems with the polysaccharide vaccine have been summarised as:

Although it is generally accepted that 23PPV is effective at preventing IPD in immune-competent adults, a 2009 meta-analysis concluded that in trials of high quality, there is no evidence of vaccine protection against IPD and that 23PPV may not be protective against either IPD or pneumonia.51 A subsequent case-control study in patients aged over 60 years concluded that 23PPV provided a significant protective effect against IPD in elderly immune-competent patients.52 However, a 2012 review of data from elderly populations concluded that low protection was possible, but differences in study designs prevent definitive conclusions.53

15.4.3 Transport, storage and handling

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017.54 Store at +2°C to +8°C. Do not freeze.

15.4.4 Dosage and administration

The dose of PCV10, PCV13 and 23PPV is 0.5 mL, administered by intramuscular injection (see section 2.2.3). 23PPV can also be administered by subcutaneous injection (see section 2.2.3), but there is an increased likelihood of injection site reactions.55

Co-administration with other vaccines

PCV10, PCV13 or 23PPV may be administered at the same time as other routine childhood vaccinations, in a separate syringe at a separate injection site (see section 2.2.7 for information about multiple injections at the same visit). The only exception is PCV13 with the quadrivalent meningococcal conjugate vaccine MCV4-D, which should be given at least four weeks after PCV13. This is because when administered concurrently, there is impairment of the immune response to some of the pneumococcal sero