On this page

1. Adverse events following immunisation
2. Surveillance objectives
3. Case definition
4. Notification criteria and procedure
5. Managing single notifications
6. Vaccination failures
7. Vaccine administration errors
8. References and additional sources of information
9. Further information
10. Appendices

1. Adverse events following immunisation

An adverse event following immunisation (AEFI) is any untoward medical occurrence that follows immunisation. It does not necessarily have a causal relationship with the vaccine.

An AEFI may be related to the vaccine itself or to its handling or administration.

The Australian Immunisation Handbook¹ (online edition) provides information about the frequency, types and management of AEFIs such as anaphylaxis.

Serious adverse events

A serious adverse event following immunisation that includes any of the following²:

• results in death
• is life threatening
• requires hospitalisation
• results in persistent or significant disability or incapacity
• results in a congenital anomaly/birth defect
• does not fit in with the common reactions for that vaccine outlined in the Australian Immunisation Handbook¹ (online edition).

Any clinical event that requires intervention to prevent one of the outcomes above may also be considered as serious².

Detailed definitions of conditions classified as serious AEFIs are available in the Australian Immunisation Handbook¹ (online edition).

Non-serious adverse event

A non-serious adverse event following immunisation is a common/expected adverse event known to be associated with the vaccine as described in the Australian Immunisation Handbook¹(online edition) or product information and does not pose a potential risk to the health of the patient². Any event that is considered by the immunisation provider or immunisation recipient to be significant, of concern, or affect confidence in future immunisations and may not fit in with the criteria for a serious AEFI can be reported.

2. Surveillance objectives

• To monitor the safety of vaccines post-licensure to:
• rapidly detect and respond to changes in the rates of known adverse events following immunisation (AEFIs), and
• rapidly detect, investigate and respond to AEFIs of concern or significance
• Contribute to national surveillance and signal detection of new and emerging AEFIs or AESIs by ensuring timely notification of AEFIs to the Therapeutic Goods Administration (TGA)
• Support clinicians, including assistance in provision of advice for further immunisation doses, and
• To maintain public confidence in vaccines and the National Immunisation Program (NIP).

3. Case definition

Suspected case

A suspected case is any adverse event, either serious or non-serious, that occurs after vaccination and is considered to be possibly related to that vaccination.

Factors to be considered in case identification

• An AEFI can be coincidentally associated with immunisation without being caused by the vaccine or the immunisation process². The notification of a suspected AEFI does not imply a causal association with vaccination.
• The time interval from vaccination to onset may be relevant to causal determination but will depend on the adverse reaction². As the time interval between immunisation and onset of the event may not always be accurate or well established, a time interval is not included in the case definition.
• Notification is required by doctors and hospitals. Other clinicians are able to notify suspected AEFIs with the consent of the patient.
• Non-serious AEFIs should also be carefully monitored because they may signal a potentially larger concern with the vaccine or immunisation process or may have an impact on the acceptability of immunisation in general². Non-serious adverse events that have been reported to the PHU, should be entered into the Notifiable Conditions Information Management System (NCIMS).

4. Notification criteria and procedure

AEFIs are notifiable conditions under the NSW Public Health Act (2010). Notification is required by doctors and hospitals.

Suspected cases should be entered onto the NCIMS by the PHU.

Serious AEFIs and those reported to a school-based immunisation team on the day of vaccination should be reported directly to the NSW Health Immunisation Unit as well as being entered onto the NCIMS.

5. Managing single notifications

Investigation

Follow-up information of the notification will be obtained from the treating clinicians, medical records and/or patients/carers as appropriate.

Response times

The expected timeframe to report AEFIs is aligned with the level, likely causality and significance of the adverse event.

Suspected AEFI (see Case Definition) may be:

• common and/or unlikely to be causally related to immunisation (low level),
• uncommon and serious with potential relationship with recent immunisation (high level) or
• uncommon and significant (high level of significance) with a likely causal link to immunisation, or likely significant media or community concern in relation to the relationship with recent immunisation.

Low level adverse events

Low level adverse events are adverse events which have a low level of concern in relation to immunisation. Low level adverse events include common and expected (non-serious) reactions for the vaccine (as outlined in the Australian Immunisation Handbook¹ (online edition) or that are described in the product information), and other acute clinical events occurring in proximity to immunisation, but which are not considered as adverse events of special interest (AESI) and are not known to be causally linked to immunisation.

• Any event that is considered by the notifying practitioner or immunisation recipient to be significant, of concern, or to affect confidence in future immunisations and which may not fit in with the criteria for a serious AEFI may be reported to the TGA. Low level reports will not normally require any further investigation by the PHU.
• Low level events include (but are not limited to) acute clinical episodes such as deep vein thrombosis (DVT), cerebrovascular accident (CVA) or non-ST-elevation myocardial infarction (NSTEMI) occurring in proximity to immunisation, but which are not considered as adverse events of special interest (AESI) and are not known or suspected to be causally linked to immunisation.

Information in relation to low level events should be gathered and reported to the TGA within 7 working days.

Notification to the TGA should occur via the routine automated TGA reporting process in the NCIMS. Data transmitted to the TGA should be de-identified.

High level adverse events

High level adverse events are conditions which are known or suspected to be causally related to immunisation and have resulted in death and/or critical care admission and/or are of special interest (AESIs).

• All high level AEFIs require discussion with the PHU Director. TGA notification of these high-level adverse events should occur within 3 days, unless the event is also significant, as determined by the PHU Director, in which case reporting may be required within 24 hours.
• Notification of the initial case information will occur via the routine automated TGA reporting process in the NCIMS. Additional supporting documentation is provided to the TGA as a full, de-identified case file using secure file transfer and may also include the use of case report forms (available upon request from MoH-AEFI@health.nsw.gov.au) and case classification. Some of these cases (See Appendix 1) will also require reporting to HPNSW Immunisation Unit via email to MoH-AEFI@health.nsw.gov.au

High level adverse events of significance

• High level adverse events of significance are those adverse events which have generated significant clinician and/or community concern in relation to the association with immunisation (e.g. where the death of a person has been directly attributed to immunisation), where there is media or other interest, or where a suspected serious AEFI in a child or younger person has resulted in death, critical care admission or significant impairment.
• The PHU Director is responsible for reviewing high level adverse events which are of significance, and for ensuring they are reported to HP NSW Immunisation Unit as required.
• Both the TGA and HPNSW Immunisation Unit should be notified within 24 hours of reporting. TGA reporting occurs as for high level adverse events. The PHU Director is responsible for ensuring notification to HPNSW, Immunisation Unit via email to MoH-AEFI@health.nsw.gov.au.

Data entry

• Suspected high level cases of significance should be entered onto the notifiable diseases database within 1 working day following notification. The purpose of the initial report is to notify suspected serious AEFI to the TGA to enable timely detection of potential vaccine safety signals. A report must be made as quickly as possible, even if not all details have been obtained, so that an immediate decision can be made on the need for action and investigation. Updated information should be entered as soon as it becomes available.
• Other suspected high level cases (but not of significance) should be entered onto the notifiable diseases database within 3 working days following notification.
• Suspected low level cases should be entered onto the notifiable diseases database within 7 working days following notification.

Response procedure

Case investigation

For all cases collect information about the case using the Adverse Event Following Immunisation Form [PDF].

The response to a notification will normally be carried out in collaboration with the medical practitioner caring for the patient. But regardless of who does the follow-up, PHU staff should ensure that action has been taken to:

• confirm the onset date and symptoms of the illness
• seek the doctor's permission to contact the case or relevant caregiver
• review case management including if appropriate follow up has been arranged for advice regarding future vaccinations, if required
• confirm the date of resolution of symptoms and outcome of adverse reaction.

The Adverse Events of Special Interest (AESI) vaccine follow up form must also be completed for monitored events of special interest that have been reported in association with vaccination. The AESI vaccine follow up forms have been developed by the TGA with reference to the Brighton Collaboration Case Definitions and Guidelines for vaccine safety and include:

• Anaphylaxis
• Bell's Palsy
• Encephalitis, Myelitis or Acute Disseminated Encephalomyelitis (ADEM)
• Guillain-Barré Syndrome (GBS) including Miller Fisher Syndrome
• Hypotonic-Hyporesponsive episode (HHE)
• Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS)
• Neuritis
• Optic Neuritis
• Seizures
• Serum Sickness
• Vasculitis.

The AESI Vaccine follow up forms are available from the Immunisation Unit, Health Protection NSW.

See Appendix 1 for some examples of COVID-19 vaccine specific AEFIs/AESIs under each classification level.

Case management

The attending medical practitioner is responsible for treatment. The PHU should provide advice to the doctor regarding further immunisation if requested according to the recommendations of the latest Australian Immunisation Handbook¹ (online edition).

Additional specialist advice and facilitation of future vaccination through specialist services may be obtained from the NSW Immunisation Specialist Service on 1800 679 477 or SCHN-NSWISS@health.nsw.gov.au.

Ensure feedback has been given to the immunisation provider using the AEFI standard response letters in the NCIMS.

TGA response procedure

Suspected cases of AEFI are reported to the TGA safety monitoring program daily via the NCIMS. The TGA enters all suspected AEFI to the TGA Adverse Events Management System (AEMS). Reports are then transferred to the publicly accessible Database of Adverse Event Notifications – medicines 90 days after they have been reported to AEMS.

The TGA may refer safety concerns to the Australian Committee on Medicines (ACM) for independent advice.

6. Vaccination failures

Vaccine failure is when a disease occurs in a person even though they have received the recommended number of vaccines.

Surveillance of vaccine failures is important to monitor overall vaccine effectiveness and to identify specific problems with vaccine manufacturing or program delivery, such as cold chain breaches.

Surveillance for vaccine failures occurs through disease surveillance processes rather than AEFI surveillance processes. Public Health Units should refer to the relevant NSW Control Guidelines for management of vaccine preventable disease notifications.

The vaccination failure AESI vaccine follow up form must be completed and submitted to the TGA safety monitoring program for assessment and surveillance and the Immunisation Unit, Health Protection NSW at MOH-AEFI@health.nsw.gov.au when a vaccine failure is identified.

7. Vaccine administration errors

Vaccination administration errors can occur as a result of errors in vaccine preparation, handling, storage or administration and can be associated with immunisation error-related reactions². Identification and follow-up of vaccine administration errors can identify and correct immunisation error-related reactions in a timely manner.

It is the responsibility of the immunisation provider to manage vaccine administration errors and seek advice from the PHU if required. Vaccine administration errors resulting in a suspected adverse event following immunisation must be reported to the PHU and reported in the NCIMS.

Vaccination administration errors that may pose a safety risk to the patient, regardless of whether an adverse event following immunisation has occurred, must be reported to the TGA such as:

• Inadvertent administration of a vaccine contraindicated in pregnancy or giving a live attenuated viral vaccine during pregnancy or shortly before pregnancy due to the potential risk to the fetus¹, and
• Inadvertent administration of zoster vaccine to an immunocompromised patient due to the risk of disseminated disease from the Oka vaccine virus¹.

Vaccine administration errors that pose a safety risk to the patient must be reported to the PHU using the National Adverse Event Following Immunisation reporting form [PDF]. The notification form should be submitted to the TGA safety monitoring program and the Immunisation Unit, Health Protection NSW at MoH-AEFI@health.nsw.gov.au. An NCIMS entry is not required unless the vaccine administration error has resulted in an AEFI.

8. References and additional sources of information

Resources

• Australasian Society of Clinical Immunology and Allergy (ASCIA) for useful information for adults who have had an adverse event following immunisation and require specialist consultation.
• Vaccine safety and fact sheets, National Centre for Immunisation Research and Surveillance (NCIRS).
• Brighton Collaboration case definitions

References

1. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook (online edition), Australian Government Department of Health, Canberra, 2018.
2. World Health Organisation (WHO).Global Manual on Surveillance of Adverse Events Following Immunization, World Health Organisation, Geneva, 2016.

9. Further information

Additional information and resources about vaccine safety and avoiding adverse events following immunisation are available on the NSW Health Immunisation program Adverse Events Following Immunisation (AEFI).

10. Appendices

• Appendix 1: AEFI classification level and PHU priority and follow up timeframe
• Appendix 2: PHU management of AEFI
• Appendix 3: Suspected Thrombosis with Thrombocytopenia (TTS) classification tool
• Appendix 4: Pericarditis and Myocarditis classification tool
• Appendix 5: Decision tree algorithm for GBS: level of diagnostic certainty (adapted from Brighton Collaboration)

Appendix 1

AEFI classification level and PHU priority and follow-up timeframe

Appendix 2

PHU management of AEFI

Appendix 3

Suspected Thrombosis with Thrombocytopenia (TTS) classification tool

TGA classifications for possible, probable, and confirmed TTS cases.

• Possible:
  • Objective evidence of thrombosis (radiological, surgical or autopsy)
    and
  • Platelets <150x10^{^}9/L without history of heparin exposure
    and
  • D-dimer normal, <2xULN (ULN=0.5) or unknown
• Probable:
  • Objective evidence of thrombosis (radiological, surgical or autopsy)
    and
  • Platelets <150x10^{^}9/L without history of heparin exposure
    and
  • D-dimer ≥2xULN (ULN=0.5)
  
  

  Remain as probable even if PF4 antibodies are negative or unknown.

• Confirmed:
  • Objective evidence of thrombosis (radiological, surgical or autopsy)
    and
  • Platelets <150x10^{^}9/L without history of heparin exposure
    and
  • D-dimer ≥2xULN (ULN=0.5)
    and
  • PF4 antibodies are positive
    or
  • if case is confirmed by the TGA requested EPR or VSIG

Appendix 4

Pericarditis and Myocarditis classification tool

Appendix 5

Decision tree algorithm for GBS: level of diagnostic certainty (adapted from Brighton Collaboration)