Guillain-Barré syndrome is a serious, acute neurological autoimmune disorder characterised by inflammatory demyelination of peripheral nerves. Most patients need hospitalisation, and around 25% have respiratory failure requiring intensive care. Four percent of patients die and 14% are permanently disabled. Previous research has suggested a link between viral infections and vaccinations and Guillain-Barré syndrome.
This Canadian self-controlled interval study aimed to assess the risk of Guillain-Barré syndrome after exposure to the unadjuvanted, seasonal trivalent inactivated influenza vaccine and after seasonal influenza illness. Data were extracted from healthcare databases in Ontario, (2003-2011) to ascertain cases of and hospitalisations for Guillain-Barré syndrome, billing claims for influenza vaccination and influenza-coded health-care encounters. The data were linked to assess Guillain-Barré syndrome admissions in the 42 weeks after exposure to influenza vaccination or influenza illness. The risk of Guillain-Barré syndrome after exposure to influenza vaccination and influenza illness was separately assessed. The primary risk period was defined as 0–6 weeks after exposure to influenza illness or influenza vaccine, and the control period defined as 9-42 weeks.
Overall, 2831 incident admissions for Guillain-Barré syndrome were identified; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The results found:
• The relative risk of Guillain-Barré syndrome within 6 weeks of vaccination was 52% higher than during the control interval (relative incidence 1.52; 95% CI 1.17–1.99), with the greatest risk during weeks 2–4 after vaccination• The relative incidence within 6 weeks of an influenza-coded health-care encounter was greater than that for vaccination (15.81; 95% CI 10.28–24.32)
The researchers estimate the attributable risks to be 1.03 Guillain-Barré admissions per million vaccinations (one admission per 971,567 vaccinations), compared with 17.2 Guillain-Barré admissions per million influenza-coded health-care encounters (one admission per 58,108 influenza encounters). They present the strengths and weaknesses of their study and note that a major limitation to the study is the uncertain validity of the diagnostic codes used to identify both Guillain-Barré syndrome admissions and influenza illness.
The researchers speculate that the trigger for Guillain-Barré syndrome after influenza vaccination might be the influenza antigens contained in the vaccine. They write, “Patients considering immunisation should be fully informed of the risks of Guillain-Barré syndrome from both influenza vaccines and influenza illness, as well as the more substantial direct and indirect benefits from immunisation in terms of preventing morbidity and mortality.”
Some of the points highlighted by the authors of a related Comment article include:
• The study design (self-controlled interval study) using a variable selection of risk and control intervals can make the interpretation of the results “somewhat vague”. They acknowledge that whilst a 6 week interval is often used to show evidence of plausible causal association, other data suggest Guillain-Barré syndrome can occur 4–10 months after vaccination.• The six-week interval also has the potential to introduce type-2 error bias• Previous influenza vaccination and genetic make up could contribute an increased likelihood of developing Guillain-Barré syndrome to subsequent vaccination.
The authors of the Comment article suggest that it might be time to re-think vaccine safety evaluations. They note, “A shift which would take into account the pertinent details of already established research that highlights the fact that some post-vaccination events, particularly those of autoimmune nature, can have significantly longer latency periods than currently assumed.”