Immunisation and Allergy in Children and Adults

FOCUS | CLINICAL

Immunisation and allergy in children and adults

A case-based approach

Abigail Cheung, Kirsten P Perrett ADVERSE EVENTS following immunisation Many AEFI reactions are thought (AEFIs) in Australia have been reported to represent hypersensitivity reactions at a rate of 16.9 per 100,000 population. but are often due to other mechanisms, Background Adverse events following immunisation The most commonly reported reactions as outlined in Table 1. Many of these (AEFIs) are often attributed to vaccine include injection site reaction (ISR; 34%), are rare and out of the scope of this hypersensitivity. However, many of these pyrexia (15%), rash (15%), vomiting discussion; however, almost all warrant possible allergic reactions are unlikely to (8%), headache (6%) and pain (6%), immunisation specialist review. In the be confirmed as true vaccine allergies but with anaphylaxis comprising 0.9% of cases that follow, the authors demonstrate rather coincidental symptoms that may AEFIs reported.1 common presentations of suspected mimic an allergic reaction. One study in Victoria found that hypersensitivity reactions in children Objective suspected immediate hypersensitivity and adults, and discuss the underlying By using case studies, the authors show reactions (non-specific rash, urticaria, mechanisms and management. the variation of presentations of potential angioedema, allergic reaction [generalised] hypersensitivity AEFIs. Case studies are or anaphylaxis occurring within 60 minutes used to illustrate a general approach to of immunisation) accounted for almost a CASE 1: SALLY investigation and management of these reactions. quarter (23.5%) of all AEFIs reported in Sally, aged four years, presented two days preschool-aged children. The rate of overall after receiving her routine diphtheria/ Discussion incidence of suspected immunoglobulin tetanus/pertussis (DTPa) four-year-old AEFIs are commonly seen in general (Ig) E–mediated reaction was two per booster immunisation. She had pain practice, and it can often be difficult 100,000 doses, and the anaphylaxis rate to differentiate between the underlying and swelling around her injection site. 2 mechanisms. It is important to be able was 0.13 per 100,000 doses. The pain and swelling had commenced to identify a potential hypersensitivity True vaccine allergy, where a person approximately 24 hours after the reaction so that it can be reported to is investigated and found to have positive vaccination was administered (Figure 1). the appropriate local pharmacovigilance skin testing or a repeated hypersensitivity She was systemically well. system and patients can be reviewed reaction on challenge/revaccination, is rare; by immunisation specialists to evaluate, it is found in <10% of children investigated investigate and manage future immunisations where required. and/or challenged in a specialist allergy Pain, redness and swelling at an injection site unit following a potential vaccine is a common, expected side effect that usually hypersensitivity reaction.3 A vaccination occurs within 24 hours post-immunisation; reaction should be referred to as an AEFI it is seen following up to 34% of injections.1 until it can be categorised. Reporting these Mild ISRs may occur after any vaccine and as ‘allergic reactions’ can be a deterrent for are secondary to non-specific inflammation further vaccination, resulting in incomplete due to the injection of foreign materials immunisation coverage. or the injection itself. The majority of

ISRs are small and do not limit activity. joints, also known as extensive limb cool compress and analgesia if the child No further action is required; however, swelling. This usually occurs within remains systemically well. A severe symptomatic relief may include oral 24–72 hours after vaccine administration ISR is not a contraindication for further analgesia and cool compress. and spontaneously resolves, usually immunisations, which can be given again An ISR is classified as severe if it within a week.4 Symptomatic relief is in a primary care setting. involves the entire limb between two generally recommended, including ISRs are particularly common after repeated DTPa-containing vaccines, with approximately 20% of children reporting Table 1. Synopsis of potential immune-mediated reactions to vaccines10 an ISR and 2% reporting a severe ISR.5 ISRs after influenza vaccination are also Immune-mediated reaction Frequent clinical manifestation commonly seen, occurring in 21.2% of Immunoglobulin (Ig) Urticaria, angioedema, rhinoconjunctivitis, patients after dose one and 6% of patients E–mediated bronchospasm, gastrointestinal disorders (diarrhoea, after dose two; many of these reactions abdominal cramping, vomiting), anaphylaxis are mild.6 ISRs can be seen with any Immune complex (IgG) Vasculitis, myocarditis vaccination, with incidences reported between 5% and 30%, dependent on the T-cell mediated Maculopapular exanthema, eczema, acute generalised type of vaccination.7 exanthematous pustulosis, erythema multiforme Severe ISRs can be commonly mistaken Non IgE-mediated Urticaria, angioedema, anaphylactoid reactions, for cellulitis. However, previous studies (pseudoallergic) gastrointestinal disorders have shown swelling of both subcutaneous tissue and muscle, suggesting angioedema Autoimmune/inflammatory Thrombocytopenia, vasculitis, polyradiculoneuritis, rather than cellulitis.8 Indeed, bacterial macrophagic myofasciitis, rheumatoid arthritis, Reiter’s syndrome, sarcoidosis (juvenile), bullous pemphigoid, cellulitis post-immunisation is very rare, lichen planus, Guillain-Barré syndrome, polymyalgia and antibiotics are usually not required.

Reproduced from Chung EH, Vaccine allergies, Clin Exp Vaccine Res 2014 Jan;3(1):50–57, doi: 10.7774/ cevr.2014.3.1.5, licensed under CC BY-NC 3.0. CASE 2: USHI Ushi, aged 12 months, presented with fever and a generalised non-urticarial rash. He had received his routine 12-month immunisations (ie measles/ mumps/rubella [MMR], 13-valent pneumococcal and meningococcal ACWY vaccines) six days prior to presentation. He was well prior to the immunisations being administered but had developed malaise after five days, with fever and rash developing the morning of presentation.

There is a need to distinguish between non-allergic systemic reactions and potential vaccine hypersensitivity reactions. Systemic reactions may consist of fever and other non-specific symptoms such as malaise, myalgias or headache. Skin rashes including urticaria A B or angioedema may also present as part of a systemic reaction. These do not Figure 1. Injection site reaction17 conclusively indicate an allergic cause, a. Photograph looking directly onto the limb; b. Photograph showing the profile of the arm from behind particularly if they are delayed from Reproduced with permission from McGuire R, Photographing a severe local reaction, Parkville, Vic: MVEC, 2018, Available at https://mvec.mcri.edu.au/immunisation-references/photographing-a-severe-local- the time of immunisation. While the reaction [Accessed 31 July 2020]. underlying mechanisms for systemic reactions are unknown, it is likely that

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they occur as a result of non-specific agents, adjuvants and culture media.10 subsequently monitored in hospital with activation of the immune system. With increasing numbers of vaccines no further intervention. In this case, the delay between administered, hypersensitivity reactions vaccination and onset of reaction indicated are more commonly reported, with that it was unlikely to be secondary to a the majority of these being mild.1 The It can often be difficult to discern between hypersensitivity (IgE-mediated) reaction to most immediate and potentially severe anxiety, syncope and potential vaccine the vaccine. The delayed nature of the fever reactions are type I hypersensitivity hypersensitivity. Vasovagal syncope and rash reaction six days post-immunisation reactions, which are IgE-mediated. post-immunisation is relatively common, would be more consistent with a reaction These typically occur within minutes of particularly in the adolescent group, with a to the live-attenuated MMR vaccine, which the immunisation, and generally within female preponderance.11 In the Australian is typically seen after 5–12 days. A fever, an hour of exposure; however, delayed population, syncope has been reported which may be >39.4 °C, occurs in up to 15% reactions do rarely occur. to affect up to 10% of adolescents in of MMR vaccine recipients and can last In this case, immediate generalised association with the human papillomavirus 2–3 days.9 A systemic reaction following urticaria post-immunisation may be (HPV) immunisation.12 Tonic or clonic inactive vaccinations would be expected suggestive of a type I hypersensitivity movements are also commonly reported in within the first few days after vaccination. reaction. It is important to review patients syncopal episodes, secondary to anoxia. Given that this was not a vaccine for any signs of anaphylaxis to help stratify Factors that may help to discriminate hypersensitivity reaction, Ushi is not further management. Saanvi only had between a vasovagal episode and a at increased risk of allergic reaction or dermatological manifestations, without potential hypersensitivity (anaphylactic) anaphylaxis with future immunisations. any features of a severe reaction. She reaction are listed in Table 2. Even though the next routine would therefore not meet the criteria In Gosia’s case, there were many factors immunisations at 18 months of age for anaphylaxis. Nevertheless, referral that may create confusion regarding a include the same MMR antigens, these to a specialist immunisation unit for possible allergic reaction, including the would still be able to be administered in assessment would still be recommended. complaints of difficulty breathing. In the appropriate setting with a standard Investigation and management protocols the authors’ clinical experience, somatic observation period of at least 15 minutes tend to vary; however, one general complaints are common in vasovagal as per the guidelines of the Advisory approach and management algorithm is syncope and are likely related to underlying Committee on Immunisation Practices.7 shown in Figure 2.3 For children with a anxiety. For future immunisations, He would not need any preceding history of mild potential hypersensitivity measures for the prevention of syncope investigation. In fact, adverse events are reaction only, these authors recommend should be undertaken. These include much less common after the second dose a supervised in-hospital provocation monitoring for any presyncopal signs and of MMR or MMR in combination with test (challenge) dose when the relevant symptoms at the time of immunisation, varicella vaccine than after the first dose.7 vaccine is next required. The index and advising the patient to ensure they are vaccine challenge may be administered well hydrated to maintain blood volume, as a split dose (eg 10%, then 90%, with and to sit or lie down during and after the CASE 3: SAANVI one hour of observation between doses). immunisation (raising legs if needed until Saanvi, aged two years, was brought If this challenge is negative (non-reactive), free of symptoms). to see you for her annual influenza future vaccines can be administered in the immunisation. She had no significant community with standard observation. medical history and had been well. CASE 5: BRIDGET Her examination was normal, and the Bridget, aged 12 years, presented with influenza vaccine was administered as per CASE 4: GOSIA a history of a severe reaction after her standard protocols. Within 10 minutes, Gosia, aged 12 years, presented for routine year 7 immunisations a few Saanvi developed generalised urticaria her routine year 7 (aged 12–13 years) days prior. She reported that she had to her arms and torso but remained immunisations. She was well been well prior to the immunisation systemically well. but appeared nervous during the and had received the HPV and booster consultation. The immunisation was DTPa vaccines at school. Within administered, and within a minute, five minutes, Bridget had developed All vaccines have the potential to cause Gosia became pale and complained of generalised erythema, tightness in the IgE-mediated reactions. Almost all of difficulty breathing before collapsing. chest with wheeze and dizziness. She was the individual vaccine components On examination, her observations administered a dose of intramuscular may be considered as a possible allergic were normal and her chest remained adrenaline with good effect and sent to trigger, which may include active clear. Oxygen was applied, and she hospital by ambulance but did not require immunising antigens, conjugating agents, spontaneously regained consciousness any further treatment. preservatives, stabilisers, antimicrobial within a few minutes and was

Adverse event following immunisation (AEFI)

Vaccine advers e event reported

Potential hypersensitivity reaction: anaphylaxis, angioedema, urticarial/allergic rash, allergic reaction (generalised), non-speciﬁc rash

Specialist consultation

Immediate reaction ≤60 minutes Delayed reaction >60 minutes OR Non-anaphylaxis Delayed reaction >60 minutes AND Anaphylaxis at any time following vaccination OR Signiﬁcant clinician or parental concern

Anaphylaxis Angioedema Urticarial/allergic rash Allergic reaction (generalised) Non-speciﬁc rash

Provocation testing Skin testing Skin prick and intradermal (challenge) Immunise under supervision Immunise under in hospital (eg day medical unit) supervision in clinic For example, split dosing of index Full dose of vaccine vaccine: 10%, 90% with one hour Positive Negative (Recommend one hour between doses* (reactive) (non-reactive) of observatio n)

True vaccine allergy Positive Negative Consider skin testing (reactive) (non-reactive) alternative brand of vaccine antigens and/or vaccine components

Vaccine adverse Future vaccinations in community at event reported* general practice (primary health care) with standard observation

Figure 2. Suggested algorithm for suspected hypersensitivity reaction to vaccine3 *If suspected immunoglobulin E–mediated reaction at 10% dose, seek specialist guidance prior to proceeding with further doses Reproduced with permission from Cheung A, Choo S, Perrett KP, Vaccine allergy? Skin testing and challenge at a tertiary pediatric hospital in Melbourne, Australia, J Allergy Clin Immunol Pract 2019;7(5):1541–49, doi: 10.1016/j.jaip.2019.01.025.

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Systemic severe allergic reactions are rare However, it is important to note that identify anaphylaxis. Hence, it is useful but, obviously, important. Anaphylaxis anaphylactic reactions may occur outside to perform an MCT test within two hours is set apart from other hypersensitivity of this timeframe;13 therefore, regardless after suspected anaphylaxis, with a serum or allergic reactions by the sudden onset, of timing, any reactions consistent with baseline tryptase level measured at least rapid progression and simultaneous anaphylaxis should be referred. 48 hours post-reaction.4 involvement of several (≥2) organ systems. In Bridget’s case, her symptoms are Specific IgE tests to vaccine There are multiple criteria systems that consistent with an anaphylactic reaction, components have low predictive capacity help to define and stratify the risk of fulfilling level 1 Brighton Collaboration and are not routinely recommended anaphylaxis. One commonly used system Criteria. As such, she should be referred for evaluation.4 Skin testing (skin prick is the Brighton Collaboration Criteria.13 to a specialist immunisation service for and intradermal testing) can be useful However, it is important to note that in further investigation and guidance for for evaluating severe vaccine reactions some patients, the clinical picture may not further vaccines. and will often help to guide further be complete. Where there is uncertainty Serum mast cell tryptase (MCT) levels vaccine challenges under immunisation about the diagnosis, a referral for are useful as a retrospective marker specialist care. assessment by a specialist immunisation of anaphylaxis, although their use for As Bridget received two different service should be made. IgE-mediated vaccine-associated anaphylaxis has immunisations, it would be important for reactions generally occur soon after not been established. An acute rise in her to undergo skin testing to help identify vaccination, usually within the first hour. serum tryptase post-reaction may help to which of these may have triggered her

Table 2. Clinical features that may help differentiate between a vasovagal episode and anaphylaxis7

Clinical features Vasovagal episode Anaphylaxis

Onset Immediate, usually within minutes of, Usually within 15 minutes of vaccine administration, but can or during, vaccine administration occur within hours

Respiratory symptoms Normal breathing; may be shallow, • Cough or signs but not laboured • Wheeze • Hoarseness • Stridor • Signs of respiratory distress, such as abnormally rapid breathing (tachypnoea), cyanosis or rib recession • Upper airway swelling (eg lip, tongue, throat, uvula, larynx)

Cardiovascular • Bradycardia • Tachycardia symptoms or signs • Weak/absent peripheral pulse • Weak/absent carotid pulse • Strong carotid pulse • Hypotension — sustained and no improvement without specific • Hypotension — usually transient and treatment (note: in infants and young children, limpness and corrects in supine position pallor are signs of hypotension) • Loss of consciousness — improves once in • Loss of consciousness — no improvement once in supine or supine or head-down position head-down position

Skin symptoms or signs • Generalised pallor • Pruritus (skin itchiness) • Cool, clammy skin • Generalised skin erythema (redness) • Urticaria (weals) • Angioedema (localised or general swelling of the deeper layers of the skin or subcutaneous tissues)

Gastrointestinal Nausea or vomiting • Abdominal cramps symptoms or signs • Diarrhoea • Nausea or vomiting

Neurological Person feels faint or light-headed Person has a sense of severe anxiety and distress symptoms or signs

Reproduced with permission from Australian Technical Advisory Group on Immunisation (ATAGI), Australian immunisation handbook, Canberra: DoH, 2018, available at https://immunisationhandbook.health.gov.au/resources/handbook-tables/table-clinical-features-that-may-help-differentiate-between-a-vasovagal [Accessed 31 July 2020], © 2020 Commonwealth of Australia as represented by the Department of Health.

reaction. In hospital, she had a negative In a review of influenza immunisation MMR vaccine, may be given to any skin test to the booster DTPa vaccine but a and egg allergy, there were no severe person with a food allergy, even those positive skin test to the HPV vaccine. She reactions after the immunisation.15 with food-induced anaphylaxis.14 It is, was subsequently also skin tested to an Mild side effects such as local itch, however, important to note that yellow alternative brand of HPV vaccine, which was urticaria, throat irritation, wheeze or fever and Q fever vaccines contain higher negative. For her second HPV vaccine dose, abdominal pain have been observed, amounts of residual egg protein, and the alternative brand was administered but not anaphylaxis. There was also individuals with egg allergies who require under supervision in hospital by split no correlation between preceding these vaccines should be referred for dosing, which was well tolerated. In general, allergy testing with the vaccine and the immunisation specialist review. anaphylaxis to a previous dose of a vaccine outcome of adverse reaction.16 Current is a contraindication to receiving the same international guidelines, including vaccine and the patient should be referred those published by the Australian AEFI reporting services for immunisation specialist evaluation. Society of Clinical Immunology and Each state and territory has a local Allergy (ASCIA),14 recommend that pharmacovigilance AEFI-reporting service individuals with egg allergies (including within their health department (Table 3), CASE 6: KOSTAS those with egg anaphylaxis) can safely which collaborates with and provides Kostas, aged 24 years, presented for an receive seasonal influenza vaccines. de-identified data to the Therapeutic influenza vaccination, which had been Guidelines specifically recommend Goods Administration. In Victoria and recommended due to his asthma. His vaccines containing <1 µg/dose of egg Western Australia, the Adverse Events medical history included an egg allergy ovalbumin, which includes all current Following Immunisation – Clinical with previous anaphylaxis. Kostas had influenza vaccines licensed in Australia in Assessment Network (AEFI-CAN) bridges not received the influenza immunisation 2020. The vaccine can be administered as the link between health department previously, and his general practitioner a single dose in a community immunisation surveillance reporting and clinical was concerned about administering it in clinic (which may or may not have direct assessment and management of people the primary care setting. medical practitioner supervision) followed following serious or unexpected AEFIs. by the standard 15-minute observation The AEFI-CAN vaccine safety clinics (and period. It is important to note that although vaccine safety clinics in other states and The current influenza vaccines in Australia egg allergy does not increase the risk of territories) are able to assess and manage are derived from influenza virus grown anaphylaxis to the influenza vaccine, there potential allergic reactions, which may in hens’ eggs and may potentially contain is an independent risk of anaphylaxis with include immunisation provider and/or minute traces of egg protein (ovalbumin). each immunisation; therefore, vaccines patient advice and, if required, expert There have been previous case reports should always be administered in facilities clinical consultation regarding the event of anaphylaxis to influenza vaccine in with staff able to recognise and treat and future immunisations. Table 3 lists individuals with egg allergies;14 however, anaphylaxis. regional AEFI reporting services, which this was when the amounts of egg protein The vaccines in the current National will provide details for the local vaccine were much higher than in current vaccines. Immunisation Program, including the safety clinic as needed.

Table 3. Adverse event reporting

State/territory Reporting service Telephone Website

Australian Capital Territory ACT Health Department 02 6205 2300 www.health.act.gov.au/our-services/immunisation

New South Wales Local Public Health Unit 1300 066 055 www.health.nsw.gov.au/immunisation

Northern Territory NT Department of Health 08 8922 8044 https://health.nt.gov.au

Queensland Queensland Health 07 3328 9888 www.health.qld.gov.au/cdcg/index/adverse

South Australia SA Department of Health 1300 232 272 www.sahealth.sa.gov.au

Tasmania Direct to Therapeutic Goods 1800 044 114 www.tga.gov.au Administration

Victoria SAEFVIC 1300 882 924 www.aefican.org.au

Western Australia WAVSSS 08 6456 0208 www.aefican.org.au

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2. Baxter CM, Clothier HJ, Perrett KP. Potential 16. Kelso JM, Greenhawt MJ, Li JT. Update on Conclusion immediate hypersensitivity reactions influenza vaccination of egg allergic patients. As the number of vaccines in the Australian following immunization in preschool Ann Allergy Asthma Immunol 2013;111(4):301–02. aged children in Victoria, Australia. Hum doi: 10.1016/j.anai.2013.07.030. National Immunisation Program schedule Vaccin Immunother 2018;14(8):2088–92. 17. McGuire R. Photographing a severe local reaction. increase, so too will the number of reported doi: 10.1080/21645515.2018.1460293. Parkville, Vic: MVEC, 2018. Available at https:// AEFIs. There are a variety of underlying 3. Cheung A, Choo S, Perrett KP. Vaccine allergy? mvec.mcri.edu.au/immunisation-references/ mechanisms and for many of these AEFIs, Skin testing and challenge at a tertiary pediatric photographing-a-severe-local-reaction [Accessed hospital in Melbourne, Australia. J Allergy Clin 31 July 2020]. it can often be difficult to determine Immunol Pract 2019;7(5):1541–49. doi: 10.1016/j. a cause. However, any event felt to be jaip.2019.01.025. significant and all potential hypersensitivity 4. Nilsson L, Brockow K, Alm J, et al. Vaccination and allergy: EAACI position paper, practical aspects. reactions following immunisation with Pediatr Allergy Immunol 2017;28(7):628–40. symptoms such as non-specific rash, doi: 10.1111/pai.12762. urticaria, angioedema or anaphylaxis 5. Halperin SA, Scheifele D, Mills E, et al. Nature, evolution, and appraisal of adverse events and should be reported to the appropriate local antibody response associated with the fifth pharmacovigilance service. consecutive dose of a five-component acellular pertussis-based combination vaccine. Vaccine 2003;21(19–20):2298–306. doi: 10.1016/s0264- 410x(03)00173-7. Key points 6. Wood NJ, Blyth CC, Willis GA, et al. The safety of • AEFIs are often attributed to vaccine seasonal influenza vaccines in Australian children in 2013. Med J Aust 2014;201(10):596–600. hypersensitivity. doi: 10.5694/mja13.00097. • True vaccine hypersensitivity is rare; 7. Australian Technical Advisory Group on however, many AEFIs may present Immunisation (ATAGI). Australian immunisation handbook. Canberra, ACT: DoH, 2018. Available similarly and can be difficult to at https://immunisationhandbook.health.gov.au distinguish. [Accessed 31 July 2020]. • It is important to report all potential 8. Marshall HS, Gold MS, Gent R, et al. Ultrasound hypersensitivity AEFIs to the appropriate examination of extensive limb swelling reactions after diphtheria-tetanus-acellular pertussis local pharmacovigilance services. or reduced-antigen content diphtheria- tetanus-acellular pertussis immunization in preschool-aged children. Pediatrics 2006;118(4):1501–09. doi: 10.1542/peds.2005- Authors 2890. Abigail Cheung MBBS, FRACP, Paediatric Allergist & 9. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Immunologist, Department of Allergy & Immunology, Prevention of measles, rubella, congenital Women’s and Children’s Hospital, SA; Paediatric rubella syndrome, and mumps, 2013: Summary Allergist & Immunologist, Department of Allergy & recommendations of the Advisory Committee on Immunology, Flinders Medical Centre, SA Immunization Practices (ACIP). MMWR Morb Kirsten P Perrett MBBS, FRACP, PhD, Consultant Mortal Wkly Rep 2013;62(4):1–34. Paediatrician, Departments of Allergy & Immunology 10. Chung EH. Vaccine allergies. Clin Exp Vaccine Res and General Medicine, The Royal Children’s 2014 Jan;3(1):50–57. doi: 10.7774/cevr.2014.3.1.50. Hospital, Vic; Group Leader, Population Allergy Research Group, Murdoch Children’s Research 11. Braun MM, Patriarca PA, Ellenberg SS. Institute, Vic; Honorary Principal Fellow, Department Syncope after immunization. Arch Pediatr of Paediatrics, The University of Melbourne, Vic. Adolesc Med 1997;151(3):255–59. doi: 10.1001/ [email protected] archpedi.1997.02170400041007. Competing interests: None. 12. Crawford NW, Hodgson K, Gold M, Funding: None. Buttery J, Wood N. Adverse events following HPV immunization in Australia: Provenance and peer review: Commissioned, Establishment of a clinical network. Hum externally peer reviewed. Vaccin Immunother 2016;12(10):2662–65. doi: 10.1080/21645515.2016.1192737. Acknowledgements 13. Rüggeberg JU, Gold MS, Bayas JM, This work was supported by the Victorian et al. Anaphylaxis: Case definition and Government’s Operational Infrastructure Support guidelines for data collection, analysis, and Program. KPP is supported by a Melbourne Children’s presentation of immunization safety data. Clinician Scientist Fellowship. Vaccine 2007;25(41):5675–84. doi: 10.1016/j. vaccine.2007.02.064. The authors had full access to all relevant data in this study, and supporting sources had no involvement in 14. Australasian Society of Clinical Immunology data analysis and interpretation, or in the writing of and Allergy. ASCIA guidelines – Vaccination of the article. the egg-allergic individual. Balgowlah, NSW: ASCIA, 2017. Available at www.allergy.org.au/hp/ papers/vaccination-of-the-egg-allergic-individual References [Accessed 31 July 2020]. 1. Dey A, Wang H, Quinn H, et al. Surveillance 15. Kelso JM. Administering influenza of adverse events following immunisation in vaccine to egg-allergic persons. Expert Australia: Annual report, 2018. Commun Dis Intell Rev Vaccines 2014;13(8):1049–57. (2018) 2020;44. doi: 10.33321/cdi.2020.44.12. doi: 10.1586/14760584.2014.933079. correspondence [email protected]