Estimating background rates of Guillain-Barré Syndrome in Ontario in order to respond to safety concerns during pandemic H1N1/09 immunization campaign

Abstract

BackgroundThe province of Ontario, Canada initiated mass immunization clinics with adjuvanted pandemic H1N1 influenza vaccine in October 2009. Due to the scale of the campaign, temporal associations with Guillain-Barré syndrome (GBS) and vaccination were expected. The objectives of this analysis were to estimate the number of background GBS cases expected to occur in the projected vaccinated population and to estimate the number of additional GBS cases which would be expected if an association with vaccination existed. The number of influenza-associated GBS cases was also determined.MethodsBaseline incidence rates of GBS were determined from published Canadian studies and applied to projected vaccine coverage data to estimate the expected number of GBS cases in the vaccinated population. Assuming an association with vaccine existed, the number of additional cases of GBS expected was determined by applying the rates observed during the 1976 Swine Flu and 1992/1994 seasonal influenza campaigns in the United States. The number of influenza-associated GBS cases expected to occur during the vaccination campaign was determined based on risk estimates of GBS after influenza infection and provincial influenza infection rates using a combination of laboratory-confirmed cases and data from a seroprevalence study.ResultsThe overall provincial vaccine coverage was estimated to be between 32% and 38%. Assuming 38% coverage, between 6 and 13 background cases of GBS were expected within this projected vaccinated cohort (assuming 32% coverage yielded between 5-11 background cases). An additional 6 or 42 cases would be expected if an association between GBS and influenza vaccine was observed (assuming 32% coverage yielded 5 or 35 additional cases); while up to 31 influenza-associated GBS cases could be expected to occur. In comparison, during the same period, only 7 cases of GBS were reported among vaccinated persons.ConclusionsOur analyses do not suggest an increased number of GBS cases due to the vaccine. Awareness of expected rates of GBS is crucial when assessing adverse events following influenza immunization. Furthermore, since individuals with influenza infection are also at risk of developing GBS, they must be considered in such analyses, particularly if the vaccine campaign and disease are occurring concurrently.

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination

“…First, consideration should be given to the likelihood that the event could have occurred by chance alone through assessment of the background rate of disease [22][23]. Temporal association with vaccination is often the trigger for concern, but does not define a causal relationship [22].…”

“…As with any new vaccine, evidence of safety accumulates over time due to postlicensure safety monitoring. Since we began our review, a number of studies have been published evaluating the causal relationship between the H1N1 vaccine and GBS or other AEFI with various methods throughout the world [23,[28][29][30]; some report a slight increased risk of GBS associated with H1N1 vaccine (reporting rates of verified GBS reports within the 42 day window were 0.42 and 1.75 per million H1N1 vaccinations for age <25 yrs and age ≥25 yrs) [29], and some report no increased risk [23,30]. Thus, these manuscripts support the 2003 consensus by the Institute of Medicine for seasonal influenza vaccine, that the "evidence is inadequate to accept or reject a causal relationship" rather than favoring a causal association as seen with the 1976 swine-origin vaccine [31].…”

The Expected Number of Background Disease Events during Mass Immunization in China

“…The expected number of coincident events likely to occur within one day, one week, and six weeks were calculated by multiplying the number of hypothetically vaccinated people, the background rates of selected events at selected sites, and the risk periods after receipt of a hypothetical dose of vaccine, by reference to the methods reported in Black et al 2009 [2] and Deeks et al 2011 [3].…”

“…Deeks and colleagues estimated background rates of Guillain-Barré Syndrome in Ontario while responding to safety concerns during the pandemic H1N1/09 immunization campaign [3].…”

Guillain-Barré Syndrome and Related Disorders

“…Following the recent pandemic swine fl u in 2009, another specially designed H1N1-in fl uenza vaccine was introduced. Though epidemiological studies from North America and Europe did not fi nd an increase in incidence of typical GBS among contemporary H1N1-in fl uenza vaccinees [ 15,16 ] , atypical GBS cases and cases with GBS variants were recently reported [ 17 ] .…”