Influenza Vaccine Safety in Children: Data from VAERS 1991-2001

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Influenza Vaccine Safety in Children Data from
VAERS 1991-2001

• John Iskander MD MPH
• Gina Mootrey DO MPH
• Penina Haber MPH
• Roseanne English-Bullard BS
• Karen Broder MD FAAP

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Background on VAERS

• National passive surveillance system for adverse
  events occurring after vaccination
• In operation since 11/1/1990
• Strengths/limitations of system extensively
  discussed elsewhere
• Influenza vaccine not VICP eligible since not
  universally recommended

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Study Methodology

• Reviewed reports received by VAERS
• b/w 1/1/91 and 7/16/01
• involving TIV with or without other vaccines in
  persons lt 18 y/o
• Foreign reports excluded
• Selected case series reviews
• Deaths
• Serious Neurologic Events
• Reports in Children lt 6 months
• Allergic Reactions/Anaphylaxis

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Overall Reporting Profile

• 789 total reports, represents 6.4 of influenza
  vaccine reports with known age
• 66.5 listed only influenza vaccine
• Co-administered with PPV in 12.3 of reports
• 84.4 of reports non-serious
• 67.9 symptom onset within 1 day, 77.9 within 3
  days
• M/F ratio 1.1 to 1

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TIV Reports Received by Age
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Most Common Symptom Codes by Age

• Fever most commonly reported for all age groups lt
  10 y/o
• Other commonly reported Sx include injection site
  reactions (ISRs), rash, agitation
• Convulsions among most common COSTARTS in ages
  0-24 months, rarer above age 2

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Reports Involving Only Influenza Vacccine

• 525 total reports
• 17 FDA serious
• 60.8 of reports in age groups 6-18
• MF ratio 1.11
• Most common symptom codes fever, injection site
  hypersensitivity (ISH),
• urticaria, injection site swelling
• Reported symptom onset interval
• 1 day or less 69.1
• 3 days or less 79.4

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FDA Serious Reports Involving Only Influenza
Vaccine

• Total 89
• Most common symptom codes
• Convulsion 22.5 of reports
• Fever 19.1
• Headache 12.4
• Reaction Aggravating Underlying Condition 11.2
• GBS 10.1 (n 9)

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Proportionate Morbidity Comparison

• Selected symptom codes reported
• More frequently with flu vaccine alone than with
  flu vaccination in combination
• Urticaria 15.4 vs 8.0
• Rash 9.7 vs 8.3
• Myalgia 7.8 vs 5.7
• Less frequently with flu vaccine alone
• Fever 21.5 vs 40.9
• ISH 16.6 vs 29.9
• IS pain 5.3 vs 19.3

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Comparison with Universally Recommended Vaccines

• Selected symptom codes reported
• More frequently with flu vaccine alone
• ISH 16.6 vs 14.4
• Urticaria 15.4 vs 6.6
• IS pain 5.3 vs 4.3
• Less frequently with flu vaccine alone
• Fever 21.5 vs 35.8
• Rash 9.7 vs 12.5
• Convulsion 6.7 vs 7.6

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Death Reports

• 9 unduplicated reports
• Intervals b/w vaccination and death
• 0 days - 6 weeks
• All had preexisting chronic illness and an
  indication to receive flu vaccine
• Multiple neurologic conditions 3, Asthma 2, BPD
  1, cardiac 1, Type I DM 1, HIV 1
• Know COD for 5 cases accidental asphyxiation,
  DKA, pancreatitis, encephalopathy, encephalitis
• Likely due to concomitant medication

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Guillan Barre Syndrome

• 10 unduplicated cases reviewed
• Doubt exists as to GBS Dx in 5 cases
• (3 plausible alternate Dx, 2 not hospitalized)
• 5 likely or probable cases,
• Ages 6, 9, 13, 17, 18
• 2 with onset within 14 days I received another
  vaccine (Hep B)
• 1 with likely alternative Dx (acute CMV)
• 1 with neurologic Sx prior to vaccination
• 1 with clinically consistent history no
  information about onset interval or possible
  confounding factors

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Seizure Reports

• Screened for using COSTARTS convulsion,
  convulsion grand mal, or febrile seizure
• N 60 reports under age 18
• 3 under 6 months, 17 b/w 7-24 months, 11 age 2-5,
  20 age 10-18
• 26 cases (43) associated with fever
• 70 reported flu vaccine alone only 2 with DPT
  co-administration
• 70 with Sx onset within 24 hours, 83 within 3
  days

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Allergic Reactions and/or Anaphylaxis

• 11 reports with COSTART allergic reaction or
  anaphylaxis 2 thought to be due to other
  vaccines/components
• None appear to represent true anaphylaxis
• 5 reports consistent with immediate type
  hypersensitivity one had associated respiratory
  Sx and these may have been preexisting at time of
  vaccine

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Positive Rechallenge Cases

• 5 reports with this symptom code
• Of cases available for review
• 1 recurrence of HA, unilateral eye twitching and
  same sided paresthesias (unknown if any neuro
  tests performed pt recovered fully within two
  months)
• 1 recurrence of fever, rash
• 1 recurrence of ISR
• 1 recurrence of low grade fever, myalgia (said to
  have occurred on four separate occasions)

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Reports in Children Under 6 Months

• 10 unduplicated reports
• 9/10 received other vaccines, only solo report
  involved afebrile seizure
• 1 death, 1 other serious report
• 3 reports seizures (2 with concomitant DTP
  administration)
• 2 reports fever, both with DTP administration
• 4 reports abnormal crying, all received DTP or
  DTaP

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Limitations of Analysis

• Age-specific dose distribution data
  (denominator) not available
• Confounding by indication present, especially for
  most serious reported outcomes
• Indication for vaccination not always clear from
  case report symptom text

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Conclusions

• Majority of reports involve minor AEs slightly
  increased of serious reports vs entire database
  suggests confounding by underlying disease
• School age children disproportionately
  represented up to 60 of this sample vs 17 of
  pediatric VAERS data overall
• Number of reports in children under 2 less than
  100

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Conclusions

• Relative reactogenicity of vaccine varies with
  comparison group
• co-administration with PPV may significantly
  alter symptom profile
• Serious neurologic AEs rarely reported
  causality indeterminate in many cases
• Allergic reactions involving systemic symptoms
  rarely reported