The vaccines used in the U.S. against the pandemic H1N1 flu were associated with a modestly increased risk of Guillain-Barré syndrome, researchers reported.
A meta-analysis of data from six vaccine safety surveillance systems showed that incidence of Guillain-Barré among vaccinated people more than doubled in the few weeks after the shot, compared with a longer time period after the shot, according to Daniel Salmon, PhD, of Johns Hopkins Bloomberg School of Public Health, and colleagues.
But that incidence rate ratio (IRR) translated to fewer than two excess cases per million people vaccinated, Salmon and colleagues reported online in The Lancet.
Guillain-Barré, a rare autoimmune attack on nerve cells, causes muscle weakness, sometimes paralysis, and occasionally death, the researchers noted.
It has been linked to previous vaccines, notably in the 1976 swine flu outbreak, Salmon and colleagues wrote, but evidence linking seasonal vaccines to the syndrome is weak.
The 2009-2010 pandemic led to the largest mass vaccination initiative in recent U.S. history and was accompanied by a ramped-up safety surveillance system, which early on detected a signal of excess cases of Guillain-Barré.
To confirm or refute that signal, the authors analyzed adverse events reported to six surveillance systems, including two -- the emerging infections program and the post-licensure rapid immunization safety monitoring network – that were developed specifically for the pandemic vaccine.
And four existing programs were expanded – the vaccine safety datalink program of the U.S. government, as well as databases operated by Medicare, the Department of Defense, and the Department of Veterans Affairs.
All told, the six systems reported 77 cases of Guillain-Barré in about 23 million people who received the influenza A (H1N1) 2009 monovalent inactivated vaccine, the authors reported.
To analyze a possible association, the researchers looked at whether the cases were reported within 42 days of the vaccination or during the 42-day period starting 50 days after the shot. Days 43 through 49 were used as a washout period.
If there was no association, Salmon and colleagues argued, there should be no difference in incidence between the so-called exposure period and the later comparison period.
In fact, 54 of the cases occurred in the exposure period and 23 took place in the comparison period 50 through 91 days after vaccination, they reported.
Those numbers yielded an IRR of 2.35 that was significant(P=0.0003). Assuming a background rate of Guillain-Barré of about one case per 100,000 person-years, that IRR ratio translates into about 1.6 excess cases of the syndrome per million people vaccinated, the researchers reported.
There were too few cases to investigate associations with live-attenuated vaccines or differences by vaccine manufacturer, they noted.
Salmon and colleagues cautioned that the findings could be affected by several limitations. For instance, if doctors were on the lookout for the syndrome in the wake of vaccination, it could cause diagnosis bias.
The findings might also be confounded by other factors, such as seasonality and upper-respiratory tract infection, they noted. As well, the rates would be underestimated if the vaccine gave rise to an atypical form of Guillain-Barré.
Safety monitoring did not identify any other serious adverse events associated with the vaccines, the researchers noted, adding that the vaccines "offered substantial protection against medically attended illness" caused by the pandemic flu.
Doctors and patients, they concluded, "should be assured that the benefits of influenza A (H1N1) 2009 monovalent inactivated vaccines greatly outweighed the risks."
The study had support from the U.S. government.
The authors reported no conflicts of interest.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner