Did it? So what did happen next?
Simon DobsonVaccine Evaluation Centre
BC Children’s HospitalUniversity of British Columbia
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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