1. http://www.ug.bcc.bilkent.edu.tr/~oboyac/sevdali/1/resimler.htm

2. THE EXPERIENCE WITH ‘ORS’ AFTER FLU VACCINATION IN CANADA (1997-1998 to 2002-2003) Immunization and Respiratory Infections Division Nooshin Ahmadipour, MD, MSc Robert Pless, MD, MSc Wikke Walop, PhD Theresa Tam, MD, FRCPC

3. BACKGROUND 2000-01 influenza vaccination season (Sept-March)  Detection of a “new” adverse event  initially from two provinces – AB & BC*  complaints of red eyes and respiratory symptoms  occurred within hours of flu vaccination  labelled the oculo-respiratory syndrome (ORS), and a case definition was develped * AB: Alberta; BC: British Columbia

4. BACKGROUND II The 2000 ORS case definition  Presence of ≥ 1 of the following 7 symptoms:  bilateral red eyes  respiratory symptoms (cough; wheezing; chest tightness; difficulty breathing; sore throat)  facial swelling  Occurring within 24 hours of vaccination and resolving within 48 hours of symptom onset

5. BACKGROUND III Enhanced surveillance of flu vaccine adverse events  Health Canada in consultation with provincial/territorial health authorities initiated:  an intensified surveillance of influenza vaccine safety  a supplementary questionnaire and distributed it across Canada with some annual modifications

6. BACKGROUND IV 2000-2001 influenza season  2,450 reports of AEs were received  960 (39%) met the 2000 case definition  ORS was linked essentially to one of the three vaccines distributed in 2000-01  Investigation revealed higher proportions of unsplit virions in the implicated vaccine

7. BACKGROUND V Subsequent influenza seasons  The implicated vaccine was reformulated with a similar agent used in other influenza vaccines  ORS definition was revised to include an expanded clinical spectrum and time frame  ORS continued to be reported at a lower risk and was linked to all influenza vaccines

8. OBJECTIVES  To review the experience with “ORS” in Canada:  between 2000 and 2003  and retrospectively from 1997 to 2000  To characterize ORS as an adverse reaction to flu vaccine

9. METHODS  Review the vaccine-associated adverse event (VAE) database:  case reports meeting the 2001 ORS definition  from September 1997 to March 2003

10. METHODS II ORS Case definition (revised 2001)  Presence of ≥ 1 of the following 9 symptoms:  bilateral red eyes  respiratory symptoms: cough; wheezing; chest tightness; sore throat; difficulty breathing; dysphagia; hoasrseness  facial swelling  Occuring within 24 hours of influenza vaccination with no restriction on duration

11. RESULTS I Frequency and rate (per million vaccine doses) Season 2000 - 01 2001 - 02 2002 - 03 Symptom#Rate# # ORS 1,508 * 12496510352350 ORS-like 241201912111211 Non-ORS 1,2461028308961258 All reports 2,995 * 2461,9862131,247119

12. RESULTS II Frequency and rate ( per million doses ) for ORS by season

13. RESULTS III ORS symptom rate (per million doses) in 2002-03  Red eyes: 28  Respiratory:  cough: 23  sore throat: 19  difficulty breathing: 17  chest tightness: 17  hoarseness: 12  swallowing difficulty: 10  wheezing: 9  Facial swelling: 18 ORS rate = 50

14. RESULTS VI ORS rate by symptom category per million doses2000-012001-022002-03 Only respiratory484221 Only red eyes17135 Only facial swelling453 Red eyes + ≥ 1 respiratory 402815 ORS (2001 definition) 12410350

15. RESULTS IV Rates (per million doses) for the six most common non-ORS adverse events (AEs) in 2002-03  Fatigue: 29  Headache: 28  Myalgia: 22  Fever: 17  Allergic reaction: 11  Injection site reaction: 10 ORS rate = 50

16. RESULTS V Rates (per million doses) for serious AEs reported in 2002-03  Guillain-Barré syndrome: 1.1 (n=12)  Anaphylaxis: 1.1 (n=12)  Encephalopathy: 0.3 (n=3)  Death: 0.2 (n=2)  Meningitis &/or encephalitis: 0.2 (n=2)  Bell’s palsy: 0.2 (n=2)  Exacerbation of MS: 0.1 (n=1) The above AEs have not yet been reviewed for Causal association

17. RESULTS VII Demographics of ORS cases  Female predominance: >70% of cases  Higher reporting by middle age group highest: 45-64 years of age then 25-44 mean/median age: 47/48 (age range 2-96)  Similar to the demographics for non- ORS cases

18. RESULTS VIII Symptom characteristics of ORS case reports  The syndrome was generally described as mild and self- limited  Recurrent episodes were generally described as less severe  Hospitalization rate: 2.2; 0.8; and 2.1% respectively from 2000-01 to 2002-03; it was highest among elderly and young children

19.  VAE surveillance system  passive, voluntary reporting  self-reporting  recall bias  underreporting  ORS case definition LIMITATIONS

20. LIMITATIONS II ORS case definition  Case counts included persons reporting a single symptom (non-specific)  Reports of red eyes + ≥ 1 respiratory symptoms (with or without facial swelling)  2000-01: 40 (2001 definition: 124)  2001-02: 28 (2001 definition : 103)  2002-03: 15 (2001 definition : 50)

21. DISCUSSION A manufacturing issue in 2000-01 Publicity Enhanced surveillance ORS rate remained high during the two following flu seasons Unmasking ORS

22. Vaccine safety DISCUSSION II Influenza illness Yearly influenza vaccination is recommended Vaccine efficacy Mortality Morbidity Influenza vaccine (trivalent inactivated) ORS

23.  Head of the Division: Dr. Arlene King  Immunization staff at Health Canada:  Drs. Gisell Delgado; Pedro Diaz; Helen Anyoti  Myrna Hardy, Jean Nkanza  Saundra Montano; Christine Urbano  Jassy Anthony  Provincial/territorial ORS representatives  Health care providers  Vaccine manufacturers  Vaccine recipients across Canada ACKNOWLEDGEMENTS

24. http://www.idsystem.cz/mushrooms/imgpriroda/Nature%20036.jpg