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

BACKGROUND 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

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

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

BACKGROUND IV 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  Investigation revealed higher proportions of unsplit virions in the implicated vaccine

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

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

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

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

RESULTS I Frequency and rate (per million vaccine doses) Season Symptom#Rate# # ORS 1,508 * ORS-like Non-ORS 1, All reports 2,995 * 2461, ,247119

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

RESULTS III ORS symptom rate (per million doses) in  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

RESULTS VI ORS rate by symptom category per million doses Only respiratory Only red eyes17135 Only facial swelling453 Red eyes + ≥ 1 respiratory ORS (2001 definition)

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

RESULTS V Rates (per million doses) for serious AEs reported in  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

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

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 to ; it was highest among elderly and young children

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

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)  : 40 (2001 definition: 124)  : 28 (2001 definition : 103)  : 15 (2001 definition : 50)

DISCUSSION A manufacturing issue in Publicity Enhanced surveillance ORS rate remained high during the two following flu seasons Unmasking ORS

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

 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