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

1. 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

2. 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

3. 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 < 18 y/o • Foreign reports excluded • Selected case series reviews • Deaths • Serious Neurologic Events • Reports in Children < 6 months • Allergic Reactions/Anaphylaxis

4. 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

5. TIV Reports Received by Age

6. Most Common Symptom Codes by Age • Fever most commonly reported for all age groups < 10 y/o • Other commonly reported Sx include injection site reactions (ISR’s), rash, agitation • Convulsions among most common COSTARTS in ages 0-24 months, rarer above age 2

7. Reports Involving Only Influenza Vacccine • 525 total reports • 17% “FDA serious” • 60.8% of reports in age groups 6-18 • M:F ratio 1.1:1 • 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%

8. “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)

9. 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%

10. 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%

11. 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

12. 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

13. 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

14. 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

15. 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)

16. 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

17. 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

18. Conclusions • Majority of reports involve minor AE’s; 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

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