of symptoms (Gershon et al., 1980; Simon et al., 2007; Zimmerman and Pellitieri, 1994). In addition, Zimmerman and Pellitieri (1994) reported the concomitant administration of vaccines making it difficult to determine which, if any, vaccine could have been the precipitating event. Valensin et al. (1987) was not included in the review because the mean age of the vaccinated individuals was 12 years, and the few patients aged 18 and above were not identified. These reports did not contribute to the weight of mechanistic evidence.

Described below are four publications describing clinical, diagnostic, or experimental evidence that contributed to the weight of mechanistic evidence.

Best et al. (1974) studied 36 women who were seronegative by hemagglutination inhibition (HAI) assay who received the RA 27/3 rubella vaccine. The authors reported the development of transient arthralgia in 9 of the 36 seronegative women after vaccination and transient arthritis in 6 of the 36 women. The joint symptoms usually commenced between days 13 and 21. The symptoms lasted as long as 8 days. Thirteen of the 36 subjects were tested for rubella viral excretion by culture of nasal and pharyngeal swabs. Seven of the 13 subjects tested were positive for rubella viral excretion between days 11 and 26.

The study by Mitchell et al. (1998) was described in detail in the epide-miologic evidence section on transient arthralgia in women. All 283 white vaccinees included in this study were seronegative by enzyme immunoassay (EIA) (Abbott) prior to vaccination. Patients developing arthralgia postvaccination expressed higher frequencies of the human leukocyte antigens, DR2, DR5, and DR7, but lower frequencies of DR4 and DR6 compared to the frequency of these alleles in women with arthralgia who had received a placebo, not the rubella vaccine. When examining the frequency of acute arthalgia, subjects with DR1, DR2, DR5, and DR7 had a higher rate of acute arthralgia after rubella vaccination than did subjects with these haplotypes after placebo.

Mitchell et al. (2000) reported the development of acute and chronic arthralgia and arthritis in a subset of 18- to 41-year-old women within 28 days after rubella vaccination, which contained RA 27/3. All the subjects were initially considered seronegative based on a result of < 0.999 in the Rubazyme EIA assay (Abbott Laboratories). Additional testing of the prevaccine samples for the presence of antirubella antibodies found that several subjects had rubella-specific IgG suggesting prior exposure to rubella virus. Of the subjects, the ones who developed acute and chronic arthralgia and arthritis were those who had previously been exposed but had the lowest levels of prevaccine antibodies as measured by the additional techniques. This suggests that the inability to respond to wildtype rubella during previous exposures is associated with arthropathy after the vaccine.

Tingle et al. (1983) reported six cases of transient arthralgia postvaccination with rubella vaccine. None of the patients had been previously



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