Risk of Guillain-Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany

Abstract

Purpose: A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain-Barré syndrome (GBS) and its variant Fisher syndrome (FS).

Methods: Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1-3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010.

Results: Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1-3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5-42 post-vaccination) compared with the control period (days 43-150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination.

Conclusions: The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany.

Keywords: Guillain-Barré syndrome; pandemic influenza vaccination; pharmacoepidemiology; self-controlled case series.

Figure 1

Patient flow. ^aAmong four reports that were excluded from the study because of missing date of GBS/FS, one report referred to A(H1N1) vaccination. Including this report in a sensitivity SCCS analysis altered the result only marginally. ^bDuplicate reports: Five patients with onset of GBS/FS during the study period were reported twice, each by different participating hospitals. For these patients, the report from the initially treating hospital was included in the analysis. ^cThe “not vaccinated” population contains only reports without A(H1N1) vaccination and without seasonal influenza vaccination in the season 2009/2010. Reports with A(H1N1) and/or seasonal influenza vaccination in 2009/2010 prior to 1 November 2009 were included in the population of “other reports.” ^dOut of these, 362 reports fulfilled the BC case definition (levels 1–3). ^e“Other reports” include one report with A(H1N1) vaccination prior to 1 November 2009, 54 reports with seasonal influenza vaccination prior to 1 November 2009, one report with GBS onset before seasonal influenza vaccination, three reports with unknown month of seasonal influenza vaccination, 20 reports (3.0% of all 676 GBS/FS reports) with unknown vaccination status regarding A(H1N1) and seasonal influenza vaccination, and three reports with unknown vaccination status regarding seasonal influenza vaccination. BC, Brighton Collaboration; FS, Fisher syndrome; GBS, Guillain–Barré syndrome; p.v., post-vaccination