ABCs of AEFIs: An approach to adverse events following immunization for primary care providers

Karina Top, MD, MS, FRCPC

Associate Professor of Pediatrics and Community Health & Epidemiology

Dalhousie University

7 December 2018

Disclosures

2

Disclosure of Relationship Company/Organization(s)

I have ownership interest or other financial interest in the company (i.e. stocks, stock options or other ownership interest, excluding diversified mutual funds)

I am a member of an Advisory Board or similar committee

I am a member of a Speaker’s Bureau

I am involved in research grants and funding from industry GSK

I am currently participating in or have participated in a clinical trial within the past two years

I have received honorarium, consulting fees, salary, royalty, grant‐in‐aid or other monetary support received from or expected from the company

Pfizer

I have ownership in a patent for a product referred to in the presentation or marketed by the company

I am involved in the design of clinical studies concerning the use of products manufactured by the company

My spouse or close family member(s) have commercial affiliation(s)

Objectives

• By the end of this seminar, participants will be able to:• Describe how vaccine safety is monitored in NS and

Canada and how physicians can support vaccine safety monitoring

• Develop an approach to managing patients who experience adverse events following immunization

• Identify resources to support primary care providers in managing patients with adverse events following immunization

Patients with special immunization needs

• Adverse events following immunization (AEFIs) cause concern among patients and healthcare providers regarding future vaccinations

• AEFIs may contribute to vaccine hesitancy among patients and families

• In the absence of clear, evidence-based guidance, clinicians may opt to withhold immunization from these patients putting them at risk of infectious diseases

https://allergyfacts.org.au/allergy-anaphylaxis/signs-symptoms

https://www.slideshare.net/haqinaam/adverse-events-following-immunization-aefis

Special Immunization Clinics• SICs were established in 2013 to:

• Standardize and improve clinical care of patients with previous AEFIs or underlying medical conditions

• Determine the rate of AEFI recurrence

• Develop a research platform

• The SIC network has built a national team of expert clinicians with an interest in vaccine safety

• Infectious disease specialists

• Allergists and clinical immunologists

• Other specialists on an ad hoc basis

Active SICsacross Canada

CHU de QuébecMontreal Children’s Hospital

CHU Ste-Justine

IWK HealthCentre

Children’s Hospital of EasternOntario

Hospital for Sick Children McMaster Children’s Hospital

BC Children’sHospital

Alberta Children’s HospitalStollery Children’s Hospital

Royal University Hospital

SIC Network approach

• Patients are referred by a healthcare provider:• Halifax SIC: referrals triaged to Pediatric ID clinic (IWK),

ID clinic (QE2 HSC) or Halifax Allergy Asthma Associates

• Types of referrals of particular interest:• Large local reactions (>10 cm)• Allergic symptoms <24 hours after vaccination• Fever >40°C• Hypotonic hyporesponsive episode <48 hours after

vaccination• Neurological symptoms• Other AEFI or underlying conditions of concern

SIC approach

• Patients undergo standardized assessment of the AEFI or underlying medical condition• Causality assessment of previous AEFI

• Recommendations regarding (re)vaccination are made based on network protocols

• Patients are revaccinated in the clinic

• Follow up post-vaccination

• De-nominalized clinical information is entered in national database

Patients assessed (2013–2018)971 patients screened

815 eligible

7 patients declined

181 patients scheduled or did not attend

156 not eligible or undetermined

627 patients enrolled

504 with history of AEFI59 With Pre-Existing Conditions36 Pre-Transplant Evaluations

28 Missing enrollment information 181 Allergic-like reactions

128 Injection-site reactions57 Neurological events

155 Other systemic AEFIs11 Missing AEFI type

Participant demographics%

Male Sex 49

Age, in years

<2 37

2–6 27

7–17 28

≥18 9

Province

NS 19

QC 28

ON 30

SK 4

AB 8

BC 12

AEFI types and temporally associated vaccines

11

0

10

20

30

40

50

60

70

80

Allergic-likeevents N=181

Injection-sitereactions N=128

Neurologicalevents N=57

Other systemicevents N=155

Cas

es

(%

)

DTap/Tdap (N=266)

PCV (N=159)

Rotavirus (N=60)

MMR (N=113)

Varicella (N=71)

Men C (N=84)

HPV (N=34)

Influenza (N=109)

Other (N=104)

Severity of the AEFI

0

10

20

30

40

50

60

70

Allergic-like events Injection sitereactions

Neurological events Other systemicevents

% C

ase

s

LowModerateHighSeriousUnknown

Revaccination recommendations by AEFI type

0

10

20

30

40

50

60

70

80

90

100

Allergic-like events Injection sitereactions

Neurological events Other systemicevents

% C

ase

s

Recommended

NotRecommended

Deferred

Other

Unknown

Revaccination status and outcomes

No recurrences were serious adverse events.

AEFI TYPERevaccinated with

common AgAEFI

Recurrence

Severity relative to first

event

Effect on daily activities

Allergic-like event 98 (54%) 8 (8%)Milder (7)

Same Severity (1)

No Effect (5)Limited DA (2)Unknown (1)

Injection-site reaction

62 (48%) 15 (24%)Milder (12)

Same Severity (1)More Severe (2)

No Effect (12)Limited DA (2)Unknown (1)

Neurological event 17 (30%) 1 (6%) Same Severity (1) Limited DA (1)

Other 69 (45%) 5 (7%)Milder (2)

Same Severity (3)No Effect (3)

Limited DA (2)

Total 247 (46%) 29 (12%) - -

SIC approach to reimmunization• Injection site reactions: REVACCINATE

• Arthus reactions: consider extending interval between vaccinations

• Allergic-like events: • If anaphylaxis or ORS refer to allergist for skin testing

• If onset <1 hour after vaccination, need to differentiate allergic and anxiety/vasovagal reaction refer

• Otherwise REVACCINATE

• Contraindications: anaphylaxis to vaccine, severe delayed-type hypersensitivity reactions

SIC approach to reimmunization 2

• Neurologic events: REVACCINATE• Consider risk-benefits in patients with severe neuro

events • Contraindications: flu vaccine in patients with GBS <6

wk after flu vaccination;

• Other systemic events: REVACCINATE• Hypotonic hyporesponsive episodes• Persistent crying• Apnea – monitor x 24 hours • High fever• Thrombocytopenia – if received MMR, can check

vaccine titers

Case 1

• 18 month old boy, previously healthy and fully immunized, presents for well child visit

• Receives his 4th dose DTaP-IPV-Hib booster in left deltoid

• 5 minutes later, noted to have redness and swelling of arm that extends from shoulder to elbow.

• 90 mins post-vaccination: temp 102 F

https://www.slideshare.net/haqinaam/adverse-events-following-immunization-aefis

Case 1 Discussion

• What is your diagnosis?

• What is your immediate management?

• Is this a reportable event?

• What will you suggest for the next immunization?

https://www.slideshare.net/haqinaam/adverse-events-following-immunization-aefis

Case 1 Conclusion

• Diagnosis: extensive limb swelling • Usually mild pain/discomfort, marked swelling without

induration

Case 1 Conclusion

• Management: • Symptomatic with antipyretics, analgesics and/or

antihistamines

• Reportable? • Yes, if medical attention was required

• Next immunization: • Continue with preschool booster of Tdap-IPV

• Risk of recurrence is 13-48%

Case 2

• 12 year-old female patient brought into the ED via EMS • Received her first dose of HPV9 vaccine at school.

Within 10 minutes reported feeling dizzy and nauseous, numbness in hands and arms and tingling lips.

• Benadryl 50mg was given. • 10 minutes later she was increasingly agitated and

teary and reported her tongue felt “thick” and was having trouble swallowing.

• No rash or hives observed. Epinephrine administered. • EMS arrived 10 minutes later and administered

epinephrine again and Gravol IM. • She has a history of allergies to trees, grass and cats.

Case 2 Discussion

• What is your diagnosis?

• What is your immediate management?

• Is this a reportable event?

• What will you suggest for the next immunization?

Case 2 Conclusion

• Diagnosis• Immunization stress-related response (i.e., anxiety reaction)

• Management: • Have patient sit or lie down in quiet area, provide reassurance,

encourage slow, deep breathing

• Reportable? • Yes, because emergency medical attention was required

• Next immunization: • Educate and reassure patient and family about stress response• Administer next vaccines in private setting, with support

person if helpful• Use pain management techniques: distraction, topical

anaesthetics

Immunization stress-related response vs anaphylaxis

24

Anaphylaxis Vaso-vagal syncope Sympathetic stress reaction

Nature of

the event

Life-threatening IgE

mediated allergic reaction,

induces histamine release

from tissue mast cells.

Temporary loss of

consciousness caused by

diminished blood supply to

the brain due to painful

stimuli or emotional

reaction

Complex response to stress,

induces release of adrenalin,

cortisol, hyperventilation,

hypocapnia & respiratory alkalosis

Onset Soon (5-30 minutes) after

vaccination

Before, during or soon

after vaccination

Before, during or soon after

vaccination

Clinical

Presentation

& Behaviour

Uneasiness, restlessness,

agitation

Fearfulness, light-

headedness, dizziness,

numbness, weakness

Fearfulness, light-headedness,

dizziness, numbness,

hyperventilation +/- tingling

Source: World Health Organization

Immunization stress-related response vs anaphylaxis

25

Anaphylaxis Vaso-vagal syncope Sympathetic stress reaction

Skin Hives, swollen eyes and

face, generalized rash

Pale, sweaty, cold,

clammy

Pale, sweaty, cold, clammy

Respiratory Noisy breathing with

airway constriction -

wheezing, stridor

Normal to deep

breathing

Rapid and shallow (hyperventilation)

Cardio-

vascular

↑ heart rate, ↓ blood

pressure, dysrythymias,

cardiac arrest

↓ heart rate, +/-

transient ↓ blood

pressure

↑ heart rate,

normal or elevated systolic blood

pressure

Gastro-

intestinal

Nausea, vomiting,

abdominal cramps

Nausea, vomiting Nausea, vomiting

Neurologic Loss of consciousness,

little response once supine

Transient loss of

consciousness, good

response once supine,

tonic/clonic seizure

Pseudoseizure, tremor, weakness,

tingling sensation on face or

extremities

Source: World Health Organization

Resources: AEFIs

https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety.html

Resources: Vaccine safety monitoring

https://www.cps.ca/en/documents/position/vaccine-safety-system

Take-home messages

• The SIC network has expertise in evaluation and management of patients with AEFIs

• Most patients with mild-moderate AEFI can be revaccinated safely

• SICs can support primary care providers managing patients with AEFIs

Contacts and Acknowledgements

Halifax SIC team

• Peds ID: Drs. Karina Top, Scott Halperin

• Adult : Dr. Shelly McNeil

• Allergy: Drs. Gina Lacuesta, Greg Rex

• SIC Nurse: Karen Branscombe

• Phone: 902-470-7859

• Fax: 902-470-7232

• Email: SICnurse@iwk.nshealth.ca

• SIC Project manager: Natalie Giorgis

SIC Investigators:

• Gaston De Serres, Shelley Deeks, Francois Boucher, Francisco Noya, Bruce Tapiero, Anne Pham-Huy, Shaun Morris, Jeffrey Pernica, Athena McConnell, Wendy Vaudry, Cora Constantinescu, Manish Sadarangani

• Funding

Thank you!

Questions?

Additional Resources

• Zafack JG et al, Risk of Recurrence of Adverse Events Following Immunization: A systematic review. Pediatrics, 2017;140:e20163707; http://pediatrics.aappublications.org/content/140/3/e20163707.long

• Zafack JG, Rate of Recurrence of Adverse Events Following Immunization: Results of 19 years of surveillance in Quebec, Canada. Pediatr Infect Dis J, 2018 Sep 10; https://www.ncbi.nlm.nih.gov/pubmed/30204662; https://www.sciencedaily.com/releases/2018/09/180914154344.htm

• Zafack JG, Clinical Approach Use in Medical Consultations for Allergic-Like Events Following Immunization, J Allergy Clin Immunol Pract, 2017: 5:718; https://www.ncbi.nlm.nih.gov/pubmed/27914816