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. 2013 Jun 26;8(6):e67185.
doi: 10.1371/journal.pone.0067185. Print 2013.

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011

Sharon K Greene  1 , Melisa D Rett, Claudia Vellozzi, Lingling Li, Martin Kulldorff, S Michael Marcy, Matthew F Daley, Edward A Belongia, Roger Baxter, Bruce H Fireman, Michael L Jackson, Saad B Omer, James D Nordin, Robert Jin, Eric S Weintraub, Vinutha Vijayadeva, Grace M Lee
Affiliations

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011

Sharon K Greene et al. PLoS One. .

Abstract

Background: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.

Methods: We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.

Results: Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks.

Conclusions: After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009-10 MIV/2010-11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated.

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Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: All authors except Dr. Vellozzi and Mr. Weintraub report receiving institutional support from the Centers for Disease Control and Prevention via a subcontract with America’s Health Insurance Plans. In addition, Dr. Marcy reports receiving funds for expert testimony; and for CME lectures given for the American Academy of Pediatrics, the National Foundation for Infectious Diseases, Medical Education Speakers Network, and Symposia Medicus. Dr. Belongia reports receiving unrelated research support from MedImmune LLC. Dr. Baxter reports receiving research grants from Sanofi Pasteur, Novartis, GSK and MedImmune. Dr. Omer reports being awarded the Maurice R. Hilleman Early-stage Career Investigator Award by the National Foundation for Infectious Diseases (NFID) in 2009; the award was funded by an unrestricted educational grant to the NFID from Merck and Co., Inc., but Dr. Omer had no direct interaction with Merck. No other disclosures were reported. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Influenza vaccinations and medically-attended infections, Vaccine Safety Datalink, July 2009–June 2011.
Figure 2
Figure 2. Weekly administration of influenza vaccines, by medically-attended infection status.
Weekly administration of 2009–10 monovalent inactivated influenza vaccine and 2010–11 trivalent inactivated influenza vaccine, by medically-attended infection status in prior 6 weeks (yes/no).
See this image and copyright information in PMC

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Grants and funding

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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, although the CDC reviewed and approved this report before submission.