incidence of transverse myelitis in Rochester, Minnesota, from 1970 to 1981 was 0.83 per 100,000 people (Beghi et al., 1982). Optic neuritis represents a lesion in the optic nerve behind the orbit but anterior to the optic chiasm. Well-documented cases of optic neuritis that occur following vaccination are even rarer than cases of transverse myelitis. No population-based incidence rates were identified. Chapter 3 contains a discussion of demyelinating diseases.

Evidence for Association

Biologic Plausibility

Chapter 3 contains a discussion of the biologic plausibility of a causal relation between hepatitis B vaccine and demyelinating disease. The reports suggesting a relation between vaccination and multiple sclerosis have largely been associated with hepatitis B vaccine. It has been suggested that hepatitis B vaccine might have an inherent propensity to cause demyelinating disease, and a possible mechanism has been offered (Waisbren, 1992). There is a well-established sequence homology between a short sequence of the P antigen of the hepatitis B virus and the encephalitogenic portion of rabbit myelin basic protein. Using a synthesized amino acid sequence with adjuvant, Fujinami and Oldstone (1989) induced inflammatory encephalomyelitis in rabbits. Although molecular mimicry might induce disease in humans given some vaccines or in humans with certain infections, the relevance of this specific study to the hepatitis B vaccine is questionable, since the recombinant vaccine reported to be associated with the majority of the cases does not contain the P protein. In addition, the sequence of the myelin basic protein that is encephalitogenic for rabbits is not the same as the sequence that is encephalitogenic for primates, and the region implicated in monkeys is thought to be similar to the region implicated in humans.

The initial or recurrent attacks of multiple sclerosis following a dose of hepatitis B vaccine may be a chance occurrence. This would be supported by the frequency of the disease, its onset in young adult life at the same time that the hepatitis B vaccine is often administered, the observation that the episodes have occurred at variable times (some as short as 24 hours and some as long as 6 weeks postvaccination), which would stretch the feasibility of a delayed-type hypersensitivity reaction, and the inconsistency of occurrence after any particular sequence of vaccinations. On the other hand, multiple sclerosis is thought to be an autoimmune disease that occurs in genetically susceptible individuals. Antigenic stimulation of any type in such people might precipitate either an exacerbation or even the first clinically evident attack of disease exacerbation.



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