1. Immunization Safety Office (ISO) National Immunization Program (NIP)
Influenza Reporting Trends in Adults: Vaccine Adverse Event Reporting System (VAERS), 7/1990-6/2005
Penina Haber
John Iskander
Guillermo Herrera
Kimp Walton
Frank DeStefano
Immunization Safety Office (ISO)
National Immunization Program (NIP)
NIC 2006
Authors have no financial and other conflict of interest

3. Introduction: Trivalent Influenza Vaccine in Adults*,
Influenza vaccine is the most widely used vaccine in adults in the US
The only vaccine annually administered to adults
Monitoring and assessing the safety of influenza vaccine is a critical public health function
* >18 years

4. Objectives
To evaluate reporting trends following influenza vaccination in adults >18 years by:
Age
Report severity
Adverse event type

5. Vaccine Adverse Event Reporting System (VAERS)
National passive surveillance
~receives 15,000 reports per year
Operated jointly by CDC and FDA
Reports are received from Health care providers, manufacturers, immunization programs, patients and parents
Free text description of adverse event (AE) is coded using Coding Terms for Thesaurus of Adverse Reaction (COSTART)

6. Methods
Selected all reports following influenza vaccine in adults aged >18 years, vaccinated between 7/ /2005
Influenza season: is defined as for all reports with vaccination date from July first of year one to June 30th of the following year
Serious reports: Reports involving hospitalizations, prolongation of hospitalization, death, life-threatening illness or permanent disability (according to CFR)
Non-serious reports: all other reports
Numerator data: AE reports grouped into 3 age groups (18-49, and >65 years) and into serious and non-serious reports

7. influenza vaccine coverage X US census
Methods (Cont.)
Denominator data: Influenza vaccination coverage by season and age was calculated by multiplying U.S. census data with influenza vaccine coverage from the National Health Interview Survey data (NHIS)
Reporting rates
Influenza AEs
influenza vaccine coverage X US census
Poisson regression for linear trend was applied to evaluate reporting rates by age and severity

8. Results 2,518 (13.8%) were classified as serious reports
From 7/ /2005, VAERS received 18,245 AEs following Trivalent influenza vaccinations, in adults
2,518 (13.8%) were classified as serious reports
79% of all influenza reports were after influenza vaccination alone
followed by influenza and Pneumococcal vaccine, 2,721 (15%)
In the same period, ~750 million influenza doses were administered (NHIS, U.S. census data)
Overall reporting rate of 23.5 per million vaccinees

9. Most frequently reported Adverse Events
Serious AEs
Guilian-Barré-syndrome (21%)
Asthenia (18%)
Paresthesia (16%)
Fever (16%)
Dyspnea (12%)
Non-serious AEs
Hypersensitivity at the injection site (22%)
Vasodilatation (20%)
Pain (16%)
Fever (16%)
Injection site edema (15%)

10. Influenza Vaccinations and the Number of Serious Adverse Event Reports,* by Season, VAERS 6/1990-7/2005
* Adults >18 years;

11. Influenza Vaccinations and the Number of Non-Serious Adverse Event Reports,* by Season, VAERS 6/1990-7/2005
* Adults >18 years;

12. Reporting Rates of Serious and Non-Serious Adverse Event Reports
Reporting Rates of Serious and Non-Serious Adverse Event Reports* Following Influenza Vaccination, VAERS 6/1990-7/2005
* Adults >18 years;

13. Reporting Rates of Serious and Non-Serious Adverse Event Reports following Influenza Vaccination, VAERS
Serious AEs
Non-Serious AEs
Age-group
Coefficient**
P-value
18-49
-.0074
.4334
+.0198
<.0001
50-64
-.0784
+.0087
.0297
65+
-.0250
.0010
+.0370
< .0001
All ages*
-.0340
+.0253
* > 18 years; ** log of risk ratio

14. GBS and the Association with the Swine Influenza vaccine (1976-1977)
Concerns about the risk of developing GBS after influenza vaccination have been present since the association was first noticed during (swine influenza) vaccination campaign
Relative risks ranged from for 6-or 8 weeks periods after vaccinations.
Subsequent studies of GBS and influenza vaccines found low relative risks that were not statistically significant.

15. Reporting Rates Of GBS and Non-GBS
Reporting Rates Of GBS and Non-GBS* Following Influenza Vaccination, VAERS 7/1990-6/2005
Adults >18 years; Guillain-Barre-Syndrome (GBS) accounted for a quarter of all the serious reports and showed a significant decline over time
** Haber et. Al., JAMA. 2004; 292 :

16. Onset-Interval of GBS and Non-GBS Following influenza Vaccine in VAERS 1990-2005

17. VAERS Flu GBS Follow-up Study, VAERS 1994 - 2003
Results
N %
All reports
GBS diagnosis – verified
Non-GBS - verified
Lost to Follow-up
Prior influenza vaccination
Prior illness within 4 weeks #
# Schonberger et al. reported prior illness in
62% unvaccinated vs. 33% in vaccinated

18. Conclusions
Even though there was an increase of vaccine coverage over time, the reporting rates of serious adverse events decreased significantly for all 3 age groups
The decrease in reporting rates for serious adverse events provides reassurance of the safety of influenza vaccine
GBS reports accounted for 25% of all serious reports
The increase in non-serious reports over time was not linear, it mainly occurred from and has been relatively stable since

19. I would like to acknowledge;
Acknowledgement
I would like to acknowledge;
Co-authors
VAERS team CDC/FDA
Stephen Gordon & Marla Sidey-Vener
Lu Peng-Jun, James Singleton and Barry Sirotkin