Vaccines Not Linked to Guillain-Barré, Asserts 13-Year Trial

Fran Lowry

June 26, 2013

In a retrospective study spanning 13 years and more than 30 million person-years, researchers found no evidence of an increased risk for Guillain-Barré syndrome (GBS) after vaccinations of any type, including influenza vaccination.

"If there is a risk of Guillain-Barré syndrome following any vaccine, including influenza vaccines, it is extremely low," lead author Roger Baxter, MD, codirector of the Kaiser Permanente Vaccine Study Center, Oakland, California, said in a Kaiser news release.

"GBS is an acute inflammatory polyradiculoneuropathy affecting primarily motor neurons, which in severe cases can progress to complete paralysis and even death," write Dr. Baxter and colleagues in an article published online April 11 and in the July 15 issue of Clinical Infectious Diseases.

"Estimates of GBS incidence are in the range of 1-2 cases per 100,000 person-years worldwide and increase with age," cite the authors. Causes of the syndrome are unknown, but are thought to involve an autoimmune process triggered by antigenic stimulation that results in demyelination and destruction of peripheral nerves, the authors explain.

About two thirds of cases are preceded by a gastrointestinal or respiratory infection, with Campylobacter enteritis being the most common trigger. Also implicated are influenza, cytomegalovirus, Epstein-Barr virus, HIV, and Mycoplasma pneumonia.

Case reports have linked a variety of vaccine types to GBS. The only clear association, however, has been with the 1976 A/New Jersey swine influenza vaccine, when a small but significant increase in the number of GBS cases was seen 6 weeks after vaccination. Since that time, investigations have shown either no risk or a very small attributable risk of GBS in roughly 1 case per million doses. More recently, studies assessing the risk of GBS after the 2009 H1N1 monovalent influenza vaccines in the United States found a slightly higher attributable risk ranging from 1 to 5 per million doses.

The aim of the current study was to further evaluate the possible relationship between GBS and vaccinations, using retrospective data from the Kaiser Permanente of Northern California healthcare plan accumulated over many years.

Dr. Baxter and colleagues identified 415 confirmed cases of GBS during the 13-year period from 1994 to 2006. Most cases were male (58.6%), and the mean age was 48.5 years (range, 5 - 87 years).

The researchers also found that 277 patients (66.7%) had a respiratory and/or gastrointestinal illness in the 90 days preceding the onset of GBS.

Incidence was significantly more likely to occur in the winter months (November - April), with a relative risk of 1.5, compared with in the nonwinter months (P = .003), peaking in March.

Among the 415 patients with GBS, only 25 had received any vaccine in the 6 weeks before onset of the disease. The vaccines that were received included trivalent inactivated influenza vaccine (n = 18 patients), 23-valent polysaccharide pneumococcal vaccine (n = 2), tetanus-diphtheria combination vaccines (n = 3), hepatitis A (n = 2), and hepatitis B (n = 1).

The other 390 patients with GBS received no vaccines in the 6 weeks before onset.

The researchers also found no cases of GBS resulting from vaccines given mainly in childhood, despite the large number of doses given. These included the oral polio vaccine (1.2 million doses), measles-mumps-rubella (1.6 million), conjugated pneumococcal (1.3 million), live attenuated influenza (69,000), diphtheria-tetanus-acellular pertussis (1.9 million), varicella (764,000), Haemophilus-diphtheria-tetanus-pertussis (525,000), and Haemophilus B vaccines (1.2 million).

"For rabies vaccine (13 000 doses), there was 1 case of GBS, 7.5 weeks after vaccination," the authors add.

"Despite many years of review of a very large captured population, we are unable to exclude any [and all] possible association between vaccines and GBS," the researchers note. This is in part because of the low power of the study, given the infrequency with which GBS occurs.

Highlighting another potential study limitation, the authors point out that their reviewer was able to see whether medical providers thought that GBS was caused by a vaccine, which "could have influenced the reviewer in some way."

Nonetheless, "the low numbers of GBS cases that were temporally associated with vaccination, coupled with our results, provide reassurance that the risk of GBS following any vaccine, including influenza vaccines, is extremely low," conclude Dr. Baxter and colleagues.

Dispel Fears of Vaccination

"Studies such as this recent Kaiser Permanente trial showing lack of relationship between vaccination and [GBS] are critical to help promote immunizations and dispel fears," said Marian Michaels, MD, from the Division of Pediatric Infectious Diseases at Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, when Medscape Medical News asked for her views on this article.

"Immunizations are the most important methods we have to prevent infection and improve health," she continued. "However, too often, people hear of someone who had an illness temporarily associated with having received an immunization. By nature, we as humans try to make associations, and therefore the immunization often takes the blame, even if it had nothing to do with the problem. Anecdotal cases always have this risk, so it is important to look at large numbers, not just one person, to see if a vaccine is truly to blame or not."

The Kaiser Permanente study, "which has huge numbers of people involved," is extremely helpful, Dr. Michaels said.

"It gives us the data to say 'no, there really doesn't seem to be an association.' This should help doctors, nurses, and other healthcare professionals...have the facts when they talk with families about the importance of immunization."

Others Say Study Not Convincing

All experts do not agree, however, with the conclusion of the report by Dr. Baxter and colleagues.

Nobuhiro Yuki, MD, PhD, research professor in the Department of Medicine at National University of Singapore, told Medscape Medical News he believes a few vaccines could well have caused GBS, and he finds the paper title ("Lack of Association of Guillain-Barré Syndrome With Vaccinations") misleading.

"A number of cases of GBS developing in patients who received the rabies vaccine have been reported. GBS has been associated with 2 forms of rabies vaccines, the Semple rabies vaccine and the suckling mouse brain vaccine," said Dr. Yuki, who researches GBS but was not involved in this study. "According to their study in a small population, they could not find the association of GBS with vaccines. That's all. The title is too catchy, and I have no idea why this journal accepted their paper."

The study was supported by America's Health Insurance Plans and the Centers for Disease Control. Dr. Baxter and one coauthor report financial relationships with Merck & Company, Pfizer, Sanofi-Pasteur, Novartis Vaccines, GlaxoSmithKline, and Med-Immune. Dr. Yuki has disclosed no relevant financial relationships.

Clin Infect Dis. 2013;57:197-204. Abstract

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