Randomized, double-blind, placebo-controlled trial to assess the rate of recurrence of oculorespiratory syndrome following influenza vaccination among persons previously affected

Abstract

During the 2000-2001 influenza immunization campaign in Canada, an oculorespiratory syndrome (ORS) was recognized as adverse event associated with one of the vaccines administered. The initial surveillance case definition for ORS in 2000-2001 specified onset within 24 h after vaccination and resolution within 48 h after onset; the restriction on the duration of ORS was removed from the case definition for the vaccine distributed during the 2001-2002 influenza season. The implicated vaccine contained large aggregates of unsplit virions; alterations to the manufacturing process for the vaccine distributed during 2001-2002 addressed this. A randomized, double-blind, placebo-controlled trial assessed the safety of the reformulated version in previously affected adults. The trial was halted early, after 61 participants had received an injection (34 had received vaccine, and 27 had received placebo). The vaccine-attributable recurrence rate for onset of ORS within 24 h after injection was 33% (95% confidence interval [CI], 10%-53%); for cases that resolved within 48 h, this rate was 27% (95% CI, 5%-47%). Previously affected persons should be informed of the risk of ORS recurrence but also that episodes of such recurrence are mild and well tolerated.