Neurological Adverse Events of Immunization: Experience With an Aluminum Adjuvanted Meningococcal B Outer Membrane Vesicle Vaccine

Hanne Nøkleby


Expert Rev Vaccines. 2007;6(5):863-869. 

In This Article

Guillain-Barré Syndrome & Other Serious Neurological Adverse Events Following Vaccination

Until now, medical science cannot completely explain the cause of or mechanisms behind the development of serious neurological diseases, such as multiple sclerosis (MS), autism, Guillain-Barré syndrome (GBS) or general encephalopathy. Some of the diseases have definite genetic risk factors, while others are probably linked to infections. However, this is not enough to explain the whole picture, especially why some people develop serious diseases, while others in similar situations are not affected. As all these diseases do appear from time to time without obvious reasons, some individuals will necessarily develop such ‘inexplicable’ diseases during the period after vaccination, when vaccines are administered to large groups of healthy people. This leads to the question of whether these are causal relationships or just coinciding events( Table 1 ).

The first reports of seizures, encephalopathy and other signs of neurological pathology after vaccination came shortly after whole-cell pertussis vaccine was taken into general use more than 50 years ago.[7] As pertussis became rare as a result of vaccination, the focus on adverse events increased and the vaccine coverage dropped in several countries, resulting in large pertussis outbreaks and some deaths.[8] This was the starting point for the really large epidemiological study trying to determine the relationship between pertussis vaccination and encephalopathy, the British National Childhood Encephalopathy Study (NCES). The NCES concluded that the pertussis vaccine might cause serious neurological effects in approximately one in 100,000 cases.[9] Further studies found no significantly increased risk of serious acute neurological illness after the diphtheria, tetanus and pertussis (DTP) vaccination, but the data were compatible with the concept that vaccine-induced fever could possibly lead to an illness to which the child was predisposed, such as febrile convulsions.[10] Despite many large studies, the lack of a causal relationship has never been totally accepted.[11] From a practical point of view, the problem was solved by the introduction of acellular pertussis vaccines.

Oral polio vaccine (OPV) has been the most important tool in the worldwide campaign attempting to eradicate poliomyelitis. The vaccine is inexpensive, effective and easy to administer. However, as the vaccine contains live-attenuated polio virus, there is a risk of vaccine-associated poliomyelitis (one in 2.4 million doses).[12] Therefore, many countries without endemic polio have switched to an inactivated polio vaccine.[13] A nationwide OPV vaccination campaign in Finland in 1985 raised the question of a relationship between OPV and GBS, but in-depth analysis of the data showed that the increase in GBS occurred before the vaccination campaign started.[14]

Concerns about the risk of developing GBS after vaccination have been present since the mass vaccination with the A/New Jersey/H1N1 vaccine in the USA in 1976-1977. Nearly the entire adult population was vaccinated, using more than 35 million doses of the vaccine. A significantly increased risk of GBS became evident within 6-8 weeks after vaccination, with the largest percentage of cases occurring 2-3 weeks after vaccination. The vaccine probably caused approximately one extra case of GBS per 100,000 immunized persons.[15,16] The risk was later shown to be associated with the vaccine made from the A/New Jersey/H1N1 strain. The risk of GBS from other influenza vaccines has been followed closely in several studies and has been shown to be much lower, approximately one extra case per million people vaccinated.[17] According to data from the Vaccine Adverse Event Reporting System (VAERS) database, the incidence in the USA has fallen significantly from the 1993-1994 vaccine season (0.17 per 100,000 vaccinees) to the 2002-2003 season (0.04 per 100,000 vaccinees).[18] A possible explanation of the relationship between the influenza vaccine and GBS is that the eggs used for vaccine production may have been contaminated with Campylobacter. Campylobacter infection is a well-known cause of GBS. Better control of Campylobacter infections in chicken and eggs, especially eggs used for vaccine production, might explain the contemporary reduced incidence of influenza vaccine-associated cases of GBS.[18] However, it is impossible to exclude that some influenza vaccines may represent a higher risk of GBS, independent of the Campylobacter explanation. This is an important point when discussing mass-vaccination campaigns in a possible new influenza pandemic situation.

Aseptic meningitis cases after MMR vaccination were reported from several countries pre-1992. Detailed investigations showed that the cases were related exclusively to MMR vaccines containing the Urabe mumps strain. The risk of aseptic meningitis after vaccination with this mumps vaccine was one in 10,000-15,000 people.[19] After the withdrawal of vaccines with the Urabe mumps strain, the incidence of aseptic meningitis has decreased to one in 437,000 doses or less, according to a recent study from the UK.[19]

Other neurological events after MMR vaccination are rarely seen. GBS has been reported both after vaccination with the MMR vaccine and the individual vaccine components,[20] but a large Finish study found no indication of a causal association between MMR vaccine and other neurological events other than aseptic meningitis.[21]

The hepatitis B vaccine has been linked to different serious neurological syndromes, such as GBS and transverse myelitis, but most of all to the risk of MS. MS after hepatitis B vaccination has been reported most commonly in France, possibly because France has implemented large hepatitis B vaccination campaigns among adolescents and young adults.[22] Some authors have reported an apparently plausible explanation based on the fact that hepatitis B vaccine can lead to prolonged surface antigenemia. The vaccine has, therefore, been associated with the same kind of autoimmune symptoms or diseases that might be caused by circulating immune complexes in chronic hepatitis B infection.[23] However, several large case-control studies recently reported no evidence of a link between hepatitis B vaccine and MS.[24,25]


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