Guillain-Barré Syndrome and Menactra Meningococcal Conjugate Vaccine
Guillain-Barré Syndrome and Menactra Meningococcal Conjugate Vaccine
Abstract & Commentary
By Mary-Louise Scully
Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, CA
Dr. Scully reports no consultant, stockholder, speaker’s bureau, research, or other financial relationship with any company having ties to this field of study.
Synopsis: As of October 4, 2005, the Vaccine Adverse Event Reporting System (VAERS) received five reports of Guillain-Barré syndrome after receipt of Menactra® vaccination. Although the rate of Guillain-Barré after vaccination is similar to what might be expected by chance alone, the timing of the onset of symptoms within 2 to 5 weeks after vaccination prompted the dispatch to alert physicians to report any additional cases.
Source: Guillain-Barré Syndrome Among Recipients of Menactra Meningococcal Conjugate Vaccine- United States, June-July 2005. MMWR Morb Mortal Wkly Rep. 2005;54:1023-1025.
Menactra, a quadrivalent (a, c, y, and w135) meningococcal conjugate vaccine (MCV4), was licensed in the United States on January 14, 2005. Each 0.5mL dose of MCV4 contains 4g of each capsular polysaccharide from Neisseria meningitidis serogroups A, C, Y, and W135 conjugated to 48g of diphtheria toxoid. In February 2005, the Advisory Committee on Immunization Practices (ACIP) recommended that in addition to the previous recommendations for first-year college students living in dormitories and other high-risk groups, MCV4 can be given at the preadolescent visit (ages 11-12 years) or prior to high school at 15 years if not previously vaccinated. The manufacturer distributed approximately 2.5 million doses nationally since March of 2005, though the exact number of vaccine doses actually administered is not known.
All 5 patients reported with Guillain-Barré Syndrome (GBS) were between the ages of 17-18 years and were vaccinated between June 10, 2005 and July 25, 2005. A sixth case was reported to be under investigation. The 5 cases were reported from Pennsylvania (2 cases), New York, Ohio, and New Jersey (one case each), and from 4 different vaccine lots. Each of the cases had onset of symptoms within 14-31 days after vaccination with MCV4. All 5 cases were hospitalized with compatible clinical findings of GBS, and 4 of the 5 cases had nerve conduction testing consistent with GBS.
The most severe case was an 18-year-old female who had paralysis of her arms, difficulty swallowing, and progressive respiratory compromise requiring mechanical ventilation. She was treated with IVIG and plasmapheresis. This patient was transferred to a rehabilitation facility and did improve to the point of being able to talk, sit, stand, and feed herself, 53 days after the onset of her GBS.
One case is notable in that the patient had a history of 2 previous cases of GBS after childhood vaccinations at ages 2 and 5 years. Although reduced or absent ankle, knee, and arm reflexes were noted on physical exam, no nerve conduction studies appear to have been done on this patient. The CSF analysis revealed 0 WBC/mm³ and a protein of 26 mg/dL. She was treated with IVIG, recovered, and was discharged home.
Treatment with either plasmapheresis in one case, with IVIG in 3 cases, or both plasmapheresis plus IVIG in one case was given. Only one case had an acute illness, sore throat, before the onset of neurologic symptoms. In particular, no patients reported symptoms of a bacterial gastroenteritis suggestive of Campylobacter jejuni, which has previously been identified as a precipitating factor for GBS.
No cases of GBS had been reported in the 7000 recipients of MCV4 prior to licensure of the vaccine.1 In addition, a rapid survey conducted by the CDC Vaccine Safety Datalink and other healthcare organization databases did not detect any cases of GBS in 110,000 recipients of MCV4. Data on GBS incidence in persons aged 11-19 years indicate a possible annual incidence of 1-2 cases per 100,000 years.2 This might suggest that the number of cases reported within 6 weeks of administration of MCV4 is not increased from the number expected to occur by chance alone. However, the fact that the onset of neurologic symptoms did occur within 2-5 weeks after vaccination with MCV4 prompted the dispatch to increase awareness of a possible association.
Commentary
GBS is an acute idiopathic inflammatory demyelinating peripheral neuropathy that is characterized by progressive, symmetrical muscle weakness and areflexia. It is usually associated with spontaneous remission. In the past, GBS was thought of as a single disorder, but now is felt to consist of at least 4 subtypes: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and the Miller Fisher variant (MFS). The AIDP subtype is the most common and resembles experimental autoimmune neuritis with immune mediated damage directed against peptides from the myelin proteins. The axonal subtypes, AMAN and AMSAN, are likely caused by antibodies to gangliosides that target macrophages to invade the axon at the node of Ranvier.
It is estimated that 25% of patients with GBS have had a recent Campylobacter jejuni infection, and these patients more often have axonal forms of GBS. Research has shown that the lipo-oligosaccharide from the C. jejuni bacterial wall contains ganglioside-like structures that, when injected into rabbits, induce an acute motor axonal type neuropathy.3 GBS has been thought to be associated with a variety of systemic and infectious processes, but many reports are anecdotal. One case control study of 308 GBS patients did find serologic evidence of recent infection with Campylobacter, cytomegalovirus, or Epstein-Barr virus.4 No illness, viral or bacterial, seemed to pre-date the onset of neurologic symptoms in 4 out of the 5 GBS cases.
Concerns that immunizations might trigger GBS in susceptible persons are not new. In particular, the swine flu vaccine of 1976 was associated with a slightly increased incidence of GBS. When data on GBS reported for the 1992-1993 and 1993-1994 influenza seasons were combined, it was found that influenza vaccination resulted in approximately one additional case of GBS per million doses given.5 This GBS risk is much less than the risk of severe influenza. Despite many individual case reports, other conventional vaccines are not felt to be associated with an increased risk of GBS except, perhaps, brain-derived rabies vaccine, which is not available in the United States and may be followed by GBS in about one in 1000 recipients.6 Information on whether other vaccines, such as a tetanus-diphtheria booster, were given at the same time as the MCV4 vaccine in these 5 GBS patients, was not provided in the report.
Meningococcal meningitis affects approximately 2600 people each year in the United States. Physicians and the lay public respect and fear this illness that often affects young, previously healthy patients, with a peak in the United States in 17-18-year-olds. Mortality can be 15-25%, despite treatment with appropriate antibiotics. Those that do survive can be left with significant, permanent neurologic deficits. The addition of MCV4 vaccine in the battle to combat this devastating illness was welcomed by healthcare providers, and this report of a possible GBS association was indeed sobering. The current information is very preliminary, and the FDA and CDC are continuing to evaluate the issue and are asking that providers report any GBS or other significant adverse events after MCV4 to VAERS at www.vaers.hhs.gov or by phone at 800-822-7967. Also, providers are urged to report any case of GBS that occurs in any patient aged 11-19 years in accordance with state or local disease-reporting guidelines.
There has been no change in the recommendations for meningococcal vaccination, and the Vaccine Information Statement has been updated October 7, 2005, with the GBS information (www.cdc.gov/nip/publications/VIS/default.htm). MCV4 is only approved for patients between ages 11-55. The older meningococcal polysaccharide (MPSV4) vaccine remains available and is the recommended option for children 2-10 years old and adults over 55 who are at increased risk of meningococcal disease or traveling to areas of the world where meningococcal disease is common, such as Sub-Saharan Africa.
References
- Food and Drug Administration. Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine (Menactra Package Insert). Available at www.fda.gov/cber/products/mpdtrave011405.htm.
- Centers for Disease Control and Prevention. Healthcare Utilization Project Nationwide Inpatient Sample; Agency for Healthcare Research and Quality, Unpublished Data, 1989-2001.
- Hughes RA, Cornblath DR. Guillain-Barré Syndrome. Lancet. 2005;366:1653-1666.
- Jacobs BC, et al. The Spectrum of Antecedent Infections in Guillain-Barré Syndrome: A Case Control Study. Neurology. 1998;51:1110-1115.
- Lasky T, et al. The Guillain Barré Syndrome and the 1992-1993 and 1993-1994 Influenza Vaccines. N Engl J Med. 1998;339:1797-1802.
- Hemachudha T, et al. Immunologic Studies of Rabies Vaccination-Induced Guillain-Barré Syndrome. Neurology. 1988;38:375-378.
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