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On the eve of what could be the most challenging influenza immunization season in recent history, EIN members are facing questions about the H1N1 vaccine and Guillain-Barré syndrome (GBS), an uncommon immune-mediated neurologic disorder resulting in limb weakness and paralysis—questions that are likely to be asked repeatedly this fall.
An EIN member from New York posed the initial question: “Is there a potential for the prospective H1N1 swine origin vaccine to cross react with neural tissue and increase Guillain-Barré incidence?” Another member in Illinois put an interesting twist on the question: “We know of a patient who … was admitted to our hospital for variant H1N1 ‘swine flu,’ and then [was] admitted to another area hospital a few days post discharge from our institution with acute onset/rapidly progressive GBS. If [GBS is] secondary to H1N1 infection, I wonder if this forebodes a greater risk of GBS post natural infection and/or immunization.”
This prompted a reply from a member in Virginia who noted, “Given the report in the July 24 MMWR, the possibility of such a cross reaction does arise, reminiscent of the question of GBS (apparently with an expected frequency for any vaccine) after the swine flu vaccine in the mid-1970s.”
Another member in Iowa referenced a recent editorial in The Journal of Infectious Diseases and made these key points:
- The definite GBS background rate in the general population is unknown but is estimated to be very low (4 in 100,000 per year or 7 to 46 per 10,000,000 vaccinees within six weeks of any vaccination).
- To refute an association that rare, one would need to vaccinate and follow 53,500 and 1,238,000 subjects to show a ten and twofold increase in the background rate of GBS with a 5 percent error and power of 90 percent.
- Even if an association could be discounted with proper scientific evidence, erroneous public perception can prevail.
With public perception in mind, a North Carolina EIN member suggested the following talking points:
- All influenza vaccines are tested in humans prior to approval by the Food and Drug Administration. Clinical trial methods have improved substantially since 1976. We will have good safety data by the time of approval.
- The 2009 novel H1N1 influenza strain has already caused millions of infections and thousands of deaths worldwide.
- Influenza vaccines do have risks, but the benefits of both seasonal flu vaccines and the novel H1N1 vaccine greatly outweigh the risks for patients without medical contraindications.
Two responders from the Centers for Disease Control and Prevention (CDC) offered a detailed historical perspective and an assessment of efforts to monitor the safety of the current vaccine.
One CDC official noted that in the 1976 outbreak, epidemiologic investigations demonstrated a “small, but significant, risk” of GBS among adult vaccinees in the eight weeks following immunization. “The attributable risk among vaccinees was just under one case per every 100,000 persons vaccinated. Numerous assessments and re-assessments of the original data from this campaign supported this small, but statistically significant, association of this vaccine formulation with GBS; eight controlled studies supported this association, and none found evidence to the contrary. The underlying reasons for this association remain unknown.”
He referred EIN members to a recent analysis in Drug Safety and noted that “subsequent assessments of other formulations of influenza vaccine have been inconclusive. The biological data directly linking the A/NJ/1976 vaccine with anti-ganglioside antibodies is at present still hypothetical.”
“It is important to keep in mind that when assessing the potential risk of GBS following widespread use of an influenza A(H1N1) swine-origin virus vaccine, one substantial difference between the 1976 campaign and the current situation is that unlike the influenza A/NJ/76 (H1N1) virus, which resulted in an estimated 230 overall cases and one death, the current virus has already been associated with morbidity and mortality,” the responder wrote. Had the 1976 virus caused widespread human illness even on the scope of that associated with seasonal influenza, he continued, it is likely the increased risk of GBS after vaccination would have been viewed as unfortunate but acceptable to avert the considerable morbidity and mortality associated with influenza illness.
“The current 2009 A/H1N1 virus has already been associated with widespread illness and many deaths, and the potential virulence of the virus during the upcoming influenza season is not known,” he wrote. “This potentially influences the assessment of various risks and benefits of vaccination.”
Finally, an officer from CDC’s Immunization Safety Office explained that her office is working with the Emerging Infections Programs (EIP) sites to implement an active GBS case-finding protocol, which is intended to:
- identify all persons with a diagnosis of GBS who are hospitalized within EIP catchment areas in a timely fashion (ideally within one week of hospitalization)
- estimate the risk of GBS among vaccinated subjects within the six weeks following receipt of vaccine relative to the risk of GBS among unvaccinated subjects (i.e., the relative risk), adjusted for any confounding influences
- estimate the attributable risk of GBS following vaccination, should a significant relationship be found
- assess the proportion of persons with GBS who have other risk factors for subsequent development of GBS, including antecedent respiratory or gastrointestinal illness, and receipt of other vaccines besides influenza A (H1N1)
- determine the overall incidence of GBS among the population captured by the EIP sites
The CDC official noted that “participation and cooperation by ID physicians and the ID community will be critical in these ongoing surveillance efforts for possible adverse events following H1N1 vaccination.”
Physicians and others can report adverse events following immunization to the Vaccine Adverse Event Reporting System (VAERS).
E-mail the Emerging Infections Network.
The Emerging Infections Network (EIN) is a provider-based sentinel network designed to help the public-health community detect trends in emerging infectious diseases.
A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) and supported by funding from the Centers for Disease Control and Prevention, EIN tracks emerging infectious diseases and keeps the public-health community up to date with issues that are currently affecting or may soon affect members’ clinical practices. The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. The EIN listserve allows members to discuss new disease trends and difficult cases. Click here for more information or to join EIN.
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