New GBS / flu vaccine research published

November 14, 2006 at 2:35 pm

Flu Shot Ups Relative Risk of Guillain-Barré


By Michael Smith, Senior Staff Writer, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
November 13, 2006

TORONTO, Nov. 13 — A flu shot appears to increase the relative risk of Guillain-Barré syndrome by 45%, according to researchers here.

But because the occurrence of the syndrome is so rare, the increased relative risk does not appear to translate into increased hospital admissions, said David Juurlink, M.D., Ph.D., of Sunnybrook and Women’s College Health Sciences Center.

While people getting a flu shot should be told of the increased risk, “the decision to recommend vaccination against influenza should primarily be guided by evidence of its benefit,” Dr. Juurlink and colleagues concluded in the Nov. 13 issue of Archives of Internal Medicine.

The link between flu vaccination and Guillain-Barré has been a subject of controversy since 1976, when the U.S. National Influenza Immunization Program against so-called Swine Flu was halted early, partly because of reports of Guillain-Barré among recipients of the vaccine.

Since then, some studies have suggested an adjusted relative risk increase of about 70%, while other studies have seen no association, the researchers noted.

Dr. Juurlink and colleagues took advantage of individual-level data in the province of Ontario to conduct two related studies — a self-matched case series analysis of the temporal link between vaccination and Guillain-Barré, and a time-series look at Guillain-Barré hospital admissions before and after the start of a universal flu vaccination program.

The advantage of the self-matched case series approach, Dr. Juurlink and colleagues said, is that it allows patients to serve as their own controls, avoiding many confounding factors. In this study, the researcher identified 269 patients from April 1, 1993, through March 31, 2004 who were diagnosed with Guillain-Barré within 43 weeks of a vaccination in October or November.

The researchers assumed that a Guillain-Barré hospital admission within seven days of the vaccination was not linked to the shot, that admission during the next six weeks (dubbed the “risk interval”) might be linked, and that admission after the risk interval (the “control
interval”) was not associated.

Compared with the control interval, the relative incidence of hospitalization because of Guillain-Barré during the risk interval was
1.45 (with a 95% confidence interval from 1.05 to 1.99), which was statistically significant at P=0.02, Dr. Juurlink and colleagues found.

In 2000, the province of Ontario began a program of providing free flu vaccination to all residents older than six months, a program that produced a marked increase in the proportion of residents who were vaccinated.

From June 1, 1991, through March 31, 2004, the researchers identified
2,173 incident hospital admissions because of Guillain-Barré — about 170 new cases a year and approximately 14 cases per million person-years in the province.

The rate of admissions did not change after the introduction of the universal flu shot program, Dr. Juurlink and colleagues found.

“Our results must be interpreted carefully,” the researchers cautioned, because the increased relative risk corresponds to a very low absolute risk of Guillain-Barré.

“Furthermore, the lack of association on a population health level is consistent with the prevalent impression that influenza vaccine is only one of many potential causes” of the syndrome, they said.

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Action Points

* Explain to patients who ask that that the absolute risk of Guillain-Barré syndrome remains very low, and the benefit of the flu shot — in terms of preventing illness and lost work time — is high.

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Arch Intern Med. 2006;166:2217-2221.
Vol. 166 No. 20, November 13, 2006

Original Investigation
Guillain-Barré Syndrome After Influenza Vaccination in Adults

A Population-Based Study

David N. Juurlink, MD, PhD; Therese A. Stukel, PhD; Jeffrey Kwong, MD, MSc; Alexander Kopp, BA; Allison McGeer, MD, MSc; Ross E. Upshur, MD, MSc; Douglas G. Manuel, MD, MSc; Rahim Moineddin, PhD; Kumanan Wilson, MD, MSc

Arch Intern Med. 2006;166:2217-2221.

Background Whether influenza vaccination is associated with Guillain-Barré syndrome (GBS) remains uncertain.

Methods We conducted 2 studies using population-based health care data from the province of Ontario, Canada. In the first study, we used the self-matched case-series method to explore the temporal association between probable influenza vaccination (adults vaccinated during October and November) and subsequent hospitalization because of GBS. In the second study, we used time-series analysis to determine whether the institution of a universal influenza immunization program in October 2000 was associated with a subsequent increase in hospital admissions because of GBS at the population level.

Results From April 1, 1992, to March 31, 2004, we identified 1601 incident hospital admissions because of GBS in Ontario. In 269 patients, GBS was diagnosed within 43 weeks of vaccination against influenza. The estimated relative incidence of GBS during the primary risk interval (weeks 2 through 7) compared with the control interval (weeks 20 through 43) was 1.45 (95% confidence interval, 1.05-1.99; P = .02). This association persisted in several sensitivity analyses using risk and control intervals of different durations. However, a separate time-series analysis demonstrated no evidence of seasonality and revealed no statistically significant increase in hospital admissions because of GBS after the introduction of the universal influenza immunization program.

Conclusion Influenza vaccination is associated with a small but significantly increased risk for hospitalization because of GBS.

Gary N. Greenberg, MD MPH