TM Influenza Vaccine Safety in Children: Data from VAERS John Iskander MD MPH Gina Mootrey DO MPH Penina Haber MPH Roseanne English-Bullard BS Karen Broder MD FAAP

TM 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

TM 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

TM 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

TM TIV Reports Received by Age

TM 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

TM 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%

TM “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)

TM 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%

TM 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%

TM 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

TM 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

TM 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 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

TM 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

TM 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)

TM 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

TM 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

TM 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

TM 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