Published 9 September 2009, doi:10.1136/bmj.b3577
Cite this as: BMJ 2009;339:b3577

Views & Reviews

Personal View

Should I have an H1N1 flu vaccination after Guillain-Barré syndrome?

I have found myself asking the difficult question of whether to be vaccinated against H1N1 flu when I return to work as a hospital doctor this autumn. In December 2008 I developed severe Guillain-Barré syndrome but am making a good recovery.

I presented with foot drop one week after an episode of food poisoning. Nerve conduction studies showed patchy motor nerve demyelination and marked conduction block. I was admitted to the intensive care unit for invasive ventilation and supportive care for three months. During this time I had marked neuropathic pain (with "burning" skin) and also haemodynamic instability and adynamic ileus as a result of autonomic dysfunction. Serology testing was positive for Campylobacter jejuni. I had no other relevant past medical history and had had one previous seasonal flu vaccine without adverse effects.

My concern stems from the "swine influenza" vaccination programme in the United States in 1976, when 45 million people were given the influenza A(H1N1)/New Jersey/1976 vaccine. Vaccinations were suspended after 10 weeks mainly because 532 new cases of Guillain-Barré syndrome, or just under one case per 100 000 vaccinations, were reported, with a peak relative risk exceeding 12 in the two to three weeks after vaccination.¹ To put this into context, the European incidence of the syndrome is 1.2 to 1.9 cases per 100 000 people, although the incidence increases with age,² and the estimated background incidence within six weeks of any vaccination is 0.07 to 0.46 cases per 100 000 people vaccinated.³ The causal relation reported in 1976 has not, however, been found in subsequent studies of flu vaccination, although admittedly these later studies concerned seasonal rather than pandemic numbers. Studies showed a small increased risk in the 1992-3 and 1993-4 seasons,^{4 5 6} with a risk ratio of 1.7 or about one case per million people vaccinated.⁷ A Canadian study of Guillain-Barré syndrome admissions also showed a small but significantly increased risk after vaccination (risk ratio 1.45 (95% confidence interval 1.05 to 1.99; P=0.02),⁸ although no such increase in risk was seen in a smaller UK study.⁹ Several studies showed an increased risk of adverse events after flu vaccination,^{10 11} with 0.7 reports of the syndrome per million vaccinations from 1990-2005,¹² although these studies relied on case reporting so may be unreliable.

Just two questionnaire based studies have examined the risk of recurrent Guillain-Barré syndrome after flu vaccination in people with a history of the syndrome. In the first, 3.8% of 211 UK patients experienced a relapse,¹³ and in a very recent Dutch study none of 106 patients who had a flu vaccination (range 1-37, giving a total of 775 vaccinations) reported another episode of the syndrome.¹⁴

One may question why the vaccine might cause the Guillain-Barré syndrome. Infections induce activated T cells and antibodies that in the syndrome are thought to cross react with Schwann cell or axonal antigens and macrophages, producing the demyelination. Presumably the vaccine may induce a similar immune response in susceptible individuals. Evidence that Campylobacter jejuni infection causes some cases of the syndrome because of anti-ganglioside antibodies is convincing.² These are also seen in other cases of the syndrome after different infections (such as cytomegalovirus),¹⁵ but may be absent in influenza A associated Guillain-Barré syndrome,¹⁶ suggesting different immune mechanisms. One alternative hypothesis is that flu vaccine contains Campylobacter antigens, as the chickens from which eggs are used for vaccine production may be infected with Campylobacter, which is difficult to eradicate.¹⁷

Most patients have had a precipitating infection in the six weeks before onset of Guillain-Barré syndrome,² most commonly Campylobacter jejuni and cytomegalovirus,¹⁸ although in 60-70% of cases no causative organism is identified. Flu is a rare cause, thought to result in 1% of cases,¹⁵ although the proportion is likely to increase during seasonal outbreaks.^{16 19} Flu is likely to contribute to those cases where no causative organism is usually identified, as suggested by a French study, in which recent flu-like illness was reported in 30% of these cases.¹⁶ Of these patients, 14% tested positive for previous influenza A infection and all were aged under 65 years. Interestingly, they were less likely to need mechanical ventilation than patients whose episode of Guillain-Barré syndrome followed Campylobacter infection.

An important question is whether the syndrome is more likely to develop after flu vaccination or after flu infection itself. A study of 553 people with the syndrome and 5445 matched controls found an 18-fold increase in the risk of recurrence of the syndrome in the two months after flu-like illness (odds ratio 18.6 (7.5 to 46.4)), whereas the study suggested a possible protective effect of vaccination (odds ratio 0.16 (0.02 to 1.25).²⁰ A more recent, self controlled case series using 775 episodes of the syndrome showed that the relative incidence within 90 days of flu-like illness was 7.4 (4.4 to 12.4), higher within 30 days (16.6 (9.4 to 29.5)), whereas the relative incidence within 90 days of vaccination was 0.76 (0.41 to 1.4).¹⁹ These studies suggest that although flu-associated Guillain-Barré syndrome is rare, the risk is much higher than that after vaccination. Large scale flu vaccination has even been proposed as a means to protect against the syndrome.¹⁶

I do not know whether my illness was an idiosyncratic autoimmune phenomenon or whether I am predisposed to similar events in the future. It has been suggested that those who are still within six weeks of the onset of an episode of the syndrome or those whose episode was initially precipitated by vaccination should avoid the vaccine, which seems sensible. In view of the potential risks of and likely exposure to flu infection as a healthcare professional, the lack of relapse of the syndrome in a sizeable number of people who have had the flu vaccine, and the lack of a persistent causal association, my current view is to consider "having the jab" when it becomes available.

Cite this as: BMJ 2009;339:b3577

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See also Research, BMJ 2009;339:b3391, doi:10.1136/bmj.b3391.

References

1. Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, Keenlyside RA, Ziegler DW, Retailliau HF, et al. Guillain-Barré syndrome following vaccination in the National Influenza Immunization Program, United States, 1976-1977. Am J Epidemiol 1979;110:105-23.[Abstract/Free Full Text]
2. Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet 2005;366:1653-66.[CrossRef][Web of Science][Medline]
3. Evans D, Cauchemez S, Hayden FG. "Prepandemic" immunization for novel influenza viruses, "swine flu" vaccine, Guillain-Barré syndrome, and the detection of rare severe adverse events. J Infect Dis 2009;200:321-8.[CrossRef][Web of Science][Medline]
4. Kaplan JE, Katona P, Hurwitz ES, Schonberger LB. Guillain-Barré syndrome in the United States, 1979-1980 and 1980-1981: lack of an association with influenza vaccination. JAMA 1982;248:698-700.[Abstract/Free Full Text]
5. Hurwitz ES, Schonberger LB, Nelson DB, Holman RC. Guillain-Barré syndrome and the 1978-1979 influenza vaccine. N Engl J Med 1981;304:1557-61.[Abstract]
6. Roscelli JD, Bass JW, Pang L. Guillain-Barré syndrome and influenza vaccination in the US Army, 1980-1988. Am J Epidemiol 1991;133:952-5.[Abstract/Free Full Text]
7. Lasky T, Terracciano GJ, Magder L, Koski CL, Ballesteros M, Nash D, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 1998;339:1797-802.[Abstract/Free Full Text]
8. Juurlink DN, Stukel TA, Kwong J, Kopp A, McGeer A, Upshur RE, et al. Guillain-Barré syndrome after influenza vaccination in adults: a population-based study. Arch Intern Med 2006;166:2217-21.[Abstract/Free Full Text]
9. Hughes RA, Charlton J, Latinovic R, Gulliford MC. No association between immunization and Guillain-Barré syndrome in the United Kingdom, 1992 to 2000. Arch Intern Med 2006;166:1301-4.[Abstract/Free Full Text]
10. Geier MR, Geier DA, Zahalsky AC. Influenza vaccination and Guillain Barré syndrome small star, filled. Clin Immunol 2003;107:116-21.[CrossRef][Web of Science][Medline]
11. Haber P, DeStefano F, Angulo FJ, Iskander J, Shadomy SV, Weintraub E, et al. Guillain-Barré syndrome following influenza vaccination. JAMA 2004;292:2478-81.[Abstract/Free Full Text]
12. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine 2009;27:2114-20.[CrossRef][Web of Science][Medline]
13. Pritchard J, Mukherjee R, Hughes RA. Risk of relapse of Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy following immunisation. J Neurol Neurosurg Psychiatry 2002;73:348-9.[Free Full Text]
14. Kuitwaard K, Bos-Eyssen ME, Blomkwist-Markens PH, van Doorn PA. Initial symptoms, intercurrent events and long-term disability in GBS and CIDP. J Peripher Nerv Syst 2009;14(suppl):81-2.
15. Jacobs BC, Rothbarth PH, van der Meche FG, Herbrink P, Schmitz PI, de Klerk MA, et al. The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study. Neurology 1998;51:1110-5.[Abstract/Free Full Text]
16. Sivadon-Tardy V, Orlikowski D, Porcher R, Sharshar T, Durand MC, Enouf V, et al. Guillain-Barré syndrome and influenza virus infection. Clin Infect Dis 2009;48:48-56.[CrossRef][Web of Science][Medline]
17. Marwick C. Possible link between flu jab and Guillain-Barré syndrome under investigation. BMJ 2003;326:620.[Free Full Text]
18. Hughes RA, Hadden RD, Gregson NA, Smith KJ. Pathogenesis of Guillain-Barré syndrome. J Neuroimmunol 1999;100:74-97.[CrossRef][Web of Science][Medline]
19. Stowe J, Andrews N, Wise L, Miller E. Investigation of the temporal association of Guillain-Barré syndrome with influenza vaccine and influenzalike illness using the United Kingdom General Practice Research Database. Am J Epidemiol 2009;169:382-8.[Abstract/Free Full Text]
20. Tam CC, O’Brien SJ, Petersen I, Islam A, Hayward A, Rodrigues LC. Guillain-Barré syndrome and preceding infection with campylobacter, influenza and Epstein-Barr virus in the general practice research database. PLoS One 2007;2:e344.[CrossRef][Medline]

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