Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study

Summary

Background

The possible risk of Guillain-Barré syndrome from influenza vaccines remains a potential obstacle to achieving high vaccination coverage. However, influenza infection might also be associated with Guillain-Barré syndrome. We aimed to assess the risk of Guillain-Barré syndrome after seasonal influenza vaccination and after influenza-coded health-care encounters.

Methods

We used the self-controlled risk interval design and linked universal health-care system databases from Ontario, Canada, with data obtained between 1993 and 2011. We used physician billing claims for influenza vaccination and influenza-coded health-care encounters to ascertain exposures. Using fixed-effects conditional Poisson regression, we estimated the relative incidence of hospitalisation for primary-coded Guillain-Barré syndrome during the risk interval compared with the control interval.

Findings

We identified 2831 incident admissions for Guillain-Barré syndrome; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The risk of Guillain-Barré syndrome within 6 weeks of vaccination was 52% higher than in the control interval of 9–42 weeks (relative incidence 1·52; 95% CI 1·17–1·99), with the greatest risk during weeks 2–4 after vaccination. The risk of Guillain-Barré syndrome within 6 weeks of an influenza-coded health-care encounter was greater than for vaccination (15·81; 10·28–24·32). The attributable risks were 1·03 Guillain-Barré syndrome admissions per million vaccinations, compared with 17·2 Guillain-Barré syndrome admissions per million influenza-coded health-care encounters.

Interpretation

The relative and attributable risks of Guillain-Barré syndrome after seasonal influenza vaccination are lower than those after influenza illness. Patients considering immunisation should be fully informed of the risks of Guillain-Barré syndrome from both influenza vaccines and influenza illness.

Funding

Canadian Institutes of Health Research.

Introduction

Every year, seasonal influenza causes an estimated 3–5 million cases of severe illness and 250 000–500 000 deaths worldwide.¹ Immunisation remains the cornerstone for prevention, and recommendations have expanded toward universal immunisation in many jurisdictions, as well as compulsory immunisation of health-care workers.

However, the possible risk of Guillain-Barré syndrome, an acute inflammatory demyelinating polyneuropathy, from influenza vaccines remains a potential concern for large-scale immunisation programmes. The 1976 swine-origin influenza immunisation programme in the USA was halted because of reports of vaccine-associated Guillain-Barré syndrome and because the outbreak did not progress to an epidemic. This particular vaccine was associated with a four-fold to eight-fold increased risk of Guillain-Barré syndrome within 6 weeks of immunisation, or an attributable risk of one case per 100 000 people vaccinated.2, 3 Subsequent studies of seasonal influenza vaccines have reported relative risk estimates ranging from 0·16 to 1·7.4, 5, 6, 7, 8, 9, 10 These investigations were done in different years (with variation in vaccine and circulating strains) and used various study designs, some of which are susceptible to bias from confounding (eg, cohort and case-control studies). The rarity of Guillain-Barré syndrome results in many studies having limited numbers of cases and low power to study associations.

Most patients need hospitalisation, and around 25% have respiratory failure requiring intensive care.¹¹ Even with access to supportive medical care, 4% of patients die, and 14% are permanently disabled.¹² Most cases have preceding respiratory or gastrointestinal infections, most commonly Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae.13, 14 Infectious agents are believed to induce an inflammatory autoimmune response against peripheral nerves. Studies suggest that influenza infection is also strongly associated with Guillain-Barré syndrome.7, 8, 15 However, conclusions from these studies have been limited by small sample sizes or study designs susceptible to bias.

We aimed to assess the risk of Guillain-Barré syndrome after exposure to the unadjuvanted, seasonal trivalent inactivated influenza vaccine and after seasonal influenza illness.