In a large retrospective study, using a methodology that controls for seasonality, researchers at the Kaiser Permanente Vaccine Study Center did not find evidence of an increased risk of Guillain-Barré syndrome in the six-week period after vaccination with any vaccine, including influenza. The study is in the current online issue of Clinical Infectious Diseases.
Guillain-Barré syndrome is an acute disease thought to be an autoimmune disorder resulting in destruction of a nerve’s myelin sheath and peripheral nerves. In many cases, the syndrome is temporally associated with an infectious disease; most published case series report that approximately two-thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior 3 months. Guillain-Barré syndrome had been linked to the influenza vaccine in 1976, but not clearly since. There have been reports of an association with other vaccines, which have not been confirmed.
Previous studies of Guillain-Barré syndrome as a possible adverse event related to vaccines have been subject to confounding by differences between vaccinated and unvaccinated individuals which may be unmeasured, said Roger Baxter, MD, co-director of the Northern California Kaiser Permanente Vaccine Study Center, who led the team that conducted this new research. The purpose of this study was to evaluate the possible relationship between Guillain-Barré syndrome and vaccinations, using retrospective data accumulated over multiple years from a large integrated health care plan.
The Vaccine Study Center researchers further explained that variables that change over time – like infectious diseases or rates of vaccination – can lead to confusion in observational studies, which look at already collected data rather than randomizing people to treatment versus placebo. For this reason, they said, it is necessary to use special epidemiologic and statistical methods to overcome these variables.
The case-centered study design, identified by researchers at the Kaiser Permanente Vaccine Study Center and used to conduct this research, focuses on the outcome, then looks back to determine vaccination status. This method can control for many of the variables that change over time and, consequently, leads to a more accurate assessment of Guillain-Barré syndrome risk or recurrence following vaccination.
During the 13-year ascertainment period (1994-2006), 415 confirmed cases of Guillain-Barré syndrome were observed. In the 90 days preceding the onset, 277 or 66.7 percent of the cases had a respiratory or gastrointestinal illness documented, while only 25 had received any vaccine in the six weeks prior to onset.
“In this study spanning 13 years and over 30 million person-years, using a case-centered method to control for seasonality and other time-varying confounders, we did not find any association between influenza vaccine or any other vaccine and development of Guillain-Barré syndrome within six weeks following vaccination,” Baxter said. “The low numbers of Guillain-Barré syndrome cases that were temporally associated with vaccination, coupled with our results, provide reassurance that if there is a risk of Guillain-Barré syndrome following any vaccine, including influenza vaccines, it is extremely low.”
Additional authors on the study include Nicola P. Klein, MD, PhD, Bruce Fireman, MA, Paula Ray, MPH, and Edwin Lewis, MPH, with the Kaiser Permanente Vaccine Study Center; Nandini Bakshi, MD with The Permanente Medical Group; and Claudia Vellozzi, MD, MPH, with the Immunization Safety Office, Centers for Disease Control and Prevention.
This work was supported by a subcontract with America’s Health Insurance Plans (AHIP) under contract 200-2002-00732 from the Centers for Disease Control and Prevention (CDC), as a part of the Vaccine Safety Datalink (VSD).