Did it? So what did happen next?

Simon DobsonVaccine Evaluation Centre

BC Children’s HospitalUniversity of British Columbia

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I hold a patent for a product referred to in the CME/CPD program or that is marketing by a commercial organization

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Causal Association between Vaccines and Adverse Events

Did it? “individual case assessment” …… Dr. Simon Dobson

– Was an adverse event following immunization due to the vaccine(s) or immunization process…..or some other coincidental event?

– Should any further doses of the same vaccine be given in future?

Requires a valid diagnosis and appropriate investigation

Will it? “knowledge translation” …… Dr. Noni MacDonald

– How frequently will vaccine recipients experience the adverse event as a result of the vaccine?

Effective communication of evidence on vaccine related risks and benefits is essential to combat vaccine hesitancy

Can it? “knowledge generation” …… Dr. Linda Levesque

– Can the vaccine cause the adverse event, at least in certain people under certain circumstances?

Requires scientific rigour and sufficient sample size

Contraindications and Precautions for Vaccine Administration

BCCDC Immunization Manual and Canadian Immunization Guide

To investigate vaccine safety issues

To optimize the clinical management ◦ of patients with contraindication to vaccination◦ those with adverse events following immunization

(AEFI

Use as a platform for observational research Principal Investigators:

◦ Gaston De Serres, Université Laval◦ Karina Top, Scott Halperin, Canadian Center for

Vaccinology, Dalhousie University

Special Immunization Clinic Network

Special Immunization Clinic Network Goals:

Clinical evaluation, diagnosis and management of AEFIs

Understand AEFIs at the individual levelEvidence based algorithms for the next shotExperts for inquiries

Was an adverse event following immunization due to the vaccine(s) or immunization process…..or some other coincidental event?

While everything is about the conversation

There has to be some understanding as to how keen the parent(s) are to continue the series

This may not be what it seems….

Did it? Individual case assessment

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2 wave survey experiment 1,759 parents on subject of MMR Pre-intervention survey Randomly assigned to one of four groups

◦ Information refuting MMR/Autism link◦ Written text on dangers of diseases (M,M and R)◦ Images of children with M,M and R◦ Dramatic narrative

Post intervention Survey

Effective Messages

Nyhan et al Pediatrics 2014

Misperceptions about MMR and Autism Likelihood of vaccine side effects Vaccination intent for a “next child”

Effective messages: outcomes

10Nyhan et al Pediatrics 2014

Dramatic narrative◦ Increased belief in serious vaccine side effects

Refuting MMR/Autism link◦ Reduced misperceptions◦ But…decreased intent to vaccinate if attitude

already unfavourable Images of sick children

◦ Increased belief in MMR/Autism link

Effective Messages: unintended consequences

11Nyhan et al Pediatrics 2014

Public Health communications may not be effective

May increase misperceptions May decrease vaccination intention Can be counterproductive!

Effective messages; conclusions

12Nyhan et al Pediatrics 2014

Mechanisms of Adverse Events: Host immune response; Allergic reactions

Type I hypersensitivity reactions◦ Urticaria◦ Angio-edema◦ Anaphylaxis

Anaphylaxis – 3 definitionsDefinition #1 Rapid onset of symptoms Involvement of skin and/or mucosal tissue At least one of:

Respiratory compromiseHypotensionSymptoms of end organ dysfuntion

Anaphylaxis – 3 definitionsDefinition #2 Rapid onset of symptoms after likely

allergen exposure Involvement of two or more of:

Skin/mucosal tissueRespiratory compromiseHypotension with associated consequencesGastrointestinal symptoms

Anaphylaxis – 3 definitionsDefinition #3

Rapid onset of symptoms after likely allergen exposure

Hypotension

Hives 10 month old 2 month immunizations fine 4 months: within 10 minutes hives and

edema of the lower lip Adrenaline given s/c and im Rushed to ER

Signs to consider in the crunchCutaneous

Urticaria?

Mechanisms of Adverse Events:1) The immunization process Dermographism

Signs to consider in the crunchCutaneous

Urticaria?? SHOT SITE ??

Why an IgE trigger for a vaccine allergy is rare Need to have an atopic predisposition

Need to have some personal immune maturity (> 6 -12 months)

Need to be sensitized to the component

Need to be above the threshold dose of the allergenic component

40% of anaphylaxis is idiopathic

Hives 10 month old 2 month immunizations fine 4 months: within 10 minutes hives and

edema of the lower lip Adrenaline given s/c and im Rushed to ER“But doctor, did he come to any harm

because his 6 month vaccines were not given on time”

2 year old (a bit late) getting the 4th infant DTaP,Hib,IPV

Hives and possible wheeze Adrenaline given, ambulance called, then…

It is less the event than the drama that is memorable

Vaccine Adverse Events: Can it?

Strength of association Analytic bias Biologic gradient Consistency Biologic plausibility

Vaccine Adverse Events: Did it?

Previous general experience Is there another etiology It happened before to this recipient Timing

4 year old girl At 12 months had MMR and V given 4 weeks later presented with bruising Given IVIG and platelet count returned to

normal

Mother has Multiple Sclerosis

MMR and thrombocytopenia

Sauve L and Scheifele D. Do childhood vaccines cause thrombocytopenia? Paediatr Child Health;14:31–32◦ 103 cases through IMPACT, 72% after MMR◦ 12% were after 2nd dose◦ 89/95 had normal platelets 3 months later◦ BUT one serious GI bleed and one death due to an

intracranial bleed after trauma◦

“The risk of recurrence is not known, but it is thought to be low”

MMR and thrombocytopenia

Gave the pre-school MMRV, DTaP,IPV

Vaccine Adverse Events: Did it?

Previous general experience Is there another etiology It happened before to this recipient Timing

After this: 4 year old girl Pre-school shots 2 hours later: widespread hives Soon after wheezing, itchy eyes Goes to the ER

After this, therefore because of it: 4 year old girl Pre-school visit 2 hours later: widespread hives Soon after wheezing, itchy eyes Goes to the ER

◦It is all in the story……

Vaccine Adverse Events:

Did it?

Rechallenge

Mechanisms of Adverse Events:The immunization process

Poor injection technique

Vaso-vagalfaints Funny turnsHypotonic/Hyporesponsive Episode (HHE)

Long term consequences: 15 year old girl At 2 months old had received a single

immunization 2 hours later, found limp, grey and

unresponsive Paramedics ++ ER: “likely reaction to pertussis

component” MHO: “Hypotonic/Hyporesponsive

Episode”, “will never recur”

Long term consequences15 year old girl continued:

It did! At 4 months: 2 hours later; eyes rolled back and

went limp Pediatrician; “we are not doing that

again” No immunizations since

Mechanisms of Adverse Events:Host immune response

The Arthus reactionAntigen deposit is met with lots of antibodyRedness, swelling AND Pain

Mechanisms of Adverse Events: Host immune response

Systemic inflammatory responseFeverIrritabilityNauseaVomitingMuscle aches

Mechanisms of Adverse Events: Host immune response

Systemic inflammatory response - host factors:◦ Age – younger less likely◦ Gender – girls worse than boys◦ Genetics - ??◦ Previous infection◦ Previous doses of vaccine

For Adverse Events Following Immunization It is all in the story Parents remember There are individual and family

consequences to what you say Give a clear account of why you think

what happened happened If you don’t know – say so