fever and febrile seizures in nz children following 2010 trivalent inactivated influenza vaccines
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Fever and febrile seizures in NZ children following 2010 trivalent inactivated influenza vaccines. Helen Petousis-Harris, Nikki Turner , Tracey Poole, Department of General Practice and Primary Health Care Immunisation Advisory Centre University of A uckland. - PowerPoint PPT PresentationTRANSCRIPT
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Fever and febrile seizures in NZ children following 2010 trivalent inactivated influenza
vaccines
Helen Petousis-Harris, Nikki Turner, Tracey Poole, Department of General Practice and Primary Health Care
Immunisation Advisory CentreUniversity of Auckland
Co-investigators: Robert Booy, Gary Reynolds
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Background• April 2010 Western Australia detected increase in
spontaneous reporting of febrile convulsions, single brand?– Estimated 1/110 within 4-6 hours in ≤ 5 year olds
• April 2010 NZ no signals from CARM– 24th April total of 4 reports
• Rapid analysis of ED and admission data for Ak region children hospitals (1.5 million)– No more FC than normally expected (~25 each per week)
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Actions taken
Australia April 23rd• Influenza programme for
children under five years suspended
• Insufficient data on other brands to support their continued use
New Zealand April 26th• Recommendation not to
give Fluvax brand to under 5s as precaution
• Stocks of Fluvax exhausted anyway
Collaboration between Australian NCIRS, sanofi pasteur and IMAC
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Research• NZ in unique position to evaluate the safety of several brands of flu
vaccine in young children• TIVs used for 2010: Vaxigrip, Fluvax, Influvac
– All A/California/7/2009(H1N1),A/Perth/16/2009 (H3N2), B/Brisbane/60/2008– (also one monovalent A/California/7/2009(H1N1): Celvapan)
OBJECTIVES
1. Assess rate of febrile reactions following Vaxigrip and Fluvax in ≤ 5 years2. Assess rate of febrile convulsion following Vaxigrip and Fluvax in ≤ 5 years3. Assess reactogenicity of these vaccines in other age groups
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Methodology• Primary care practices (practice nurses)
identify consecutive vaccinees and run telephone questionnaire
• Administer brief 6 (7) item survey• Vaccine identified by batch number• Three 2010 studies (total of 4142 doses)
– 473 x 18 – 55 years (IMAC)– 100 x 6 years – 18 years (CSL)– 3569 x 6mos – 5 years (Sanofi) 1
1. Petousis-Harris H, Poole T, Booy R, Turner N. Fever following administration of two inactivated influenza vaccines – A survey of parents of New Zealand infants and children 5 years and under. Vaccine.(2011) 29: 2933-2937.
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Definitions• Fever either reported or measured
– If measured then defined as ≥38°C– further defined into ≥38°C, ≥39°C and ≥40°C.
• Major Febrile Events– Fever + ED/hospital visit– Fever + GI symptoms (vomiting)– Fever + musculoskeletal symptoms– Fever and malaise/lethargy– Fever and neurological symptoms
• Rigors• Altered consciousness• Convulsive seizure
– Defined as per Brighton Collaboration definitions
Bonhoeffer J. Fever as an Adverse Event following Immunisation Case Definition and Guidelines of Data Collection, analysis and Presentation. Vaccine 2003:1 -6.Bonhoeffer J, Menkes J, Gold MS, de Souza-Brito G, Fisher MC, Halsey N, et al. Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine 2004;22(5-6):557-62.
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Verification of cases
• Clinical records obtained and/or further information sought via clinician interview for following:– Sought medical attention– Reported any neurological symptoms
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Recall bias
• Ability of parents to recall events as time between vaccination and survey increased
• Logistic regression – Outcome
• fever recalled within 24 hours or not – Explanatory variables
• Lag time from vaccination to survey• Vaccine• Age and age squared in months• Summer/winter (May-Oct, Nov-Apr)
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RESULTS FOR INFANTS AND CHILDREN
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Results - recruitmentParents of children identified by
practice as having received Influenza vaccine
2586
Parents able to be contacted
2259 (87%)
Parents completed survey
2244 (99%)
Parents declined15 (1%)
Parents uncontactable
327 (13%)
There were 3188 children and 2244 parents/caregivers in our sample providing data for 3569 doses of vaccine. There was an average of 1.1 doses given per child.
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Characteristics of vaccinees
VariableVaxigrip®
N=2545
Fluvax®
N=798P Value
Mean age of vaccinees (Months) 35.05 35.25 0.79
No history of underlying medical
conditions
1854 (73%)
587 (74%) 0.7
Atopy (asthma, eczema, hayfever) 508 (20%) 150 (19%) 0.47
Cardiovascular condition 51 (2.0%) 13 (1.6%) 0.5
Other medical condition incl renal,
cancer, diabetes180 (7%) 64(8%) 0.37
Administration of paracetamol
before vaccine administration155 (6.1%) 69 (8.6%) 0.01
Mean time (days) from last dose to
questionnaire
Mean 136 days
Range 1 - 332
Mean 197 days
Range 32-332
<0.000
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Major febrile events occurring in Vaxigrip® and Fluvax® recipients
Vaxigrip®N=2545
Fluvax®N = 798
Relative Risk(95% CI)
P Value
Convulsion/seizure level 1* 0 (0%) 2 (0.38%) N/A 0.06
Convulsive seizures level 1-3 0 (0%) 3 (0.38%) N/A 0.01
Febrile with rigor/floppy/delirium 0 (0%) 12(1.5%) N/A <0.0000
Febrile with vomiting 10 (0.4%) 54 (6.8%)
17.15
(8.78 – 33.53)<0.0000
Febrile with malaise/lethargy/irritability/headache
61 (2.4%) 124 (15.5%)6.38
(4.75 – 8.56)<0.0000
*Witnessed loss of consciousness and tonic/clonic seizure.
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Comparison of febrile events in children ≤5 years following 3559 doses of 2010 flu
vaccine
0%5%
10%15%20%25%30%35%
VaxigripFluvaxInfluvac
Celvapan, 10 doses, 2 medical advice, one fever and vomiting and one fever. 3 fevers within 24 hours
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OTHER AGE GROUPS AND 2011 DATA
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6 - 9 yearsFluvax (n=42) Vaxigrip (n=36) Fluarix (n=130)
Any fever recalled
6 (14%) 0 (0%) 4 (3%)
Fever within 24 hours
5 (12%) 0 (0%) 2 (3%)
Sought medical attention
2 (5%) 0 (0%) 0 (0%)
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Youth aged 10 – 17 years
• Active surveillance (post vaccine diary)– 69 diaries post Fluvax. 1/69 fever of 38.2°C
Fluvax (n=13) Vaxigrip (n-22)
Any fever recalled
0 (0%) 0 (0%)
Fever within 24 hours
0 (0%) 0 (0%)
Sought medical attention
0 (0%) 0 (0%)
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Adults aged 18 – 70 years
• Active surveillance (post vaccine diary)– 156 diaries. No fevers– Local reactions
Fluvax (n=209) Vaxigrip (n=262)
Any fever recalled
10 (5%) 14 (5%)
Fever within 24 hours
9 (4%) 11 (4%)
Sought medical attention
1 (0.5%) 0
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Ethnicity a risk for feverChildren 6/12 – under 6 years
Fever within 24 hours0%
5%
10%
15%
20%
25%
30%
35%
40%
EuropeanMaoriPacificAsian
N=329 Male/Female 19%/26%
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Conclusions• Febrile convulsions high following a single brand of flu vaccine 13-38 per 10,000
dosesCf with:
wDTP vaccine 6-9 per 100,000MMR 25-34 per 100,000
• UK enhanced passive surveillance found 2/10,000 and 1.4/10,000 following H1N1– No excess in reporting
• Not all brands/years equivalent
• Further attention and resources to support programme design and planning and to maintain public confidence.
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Thank you