Evidence for Association

Biologic Plausibility

Mumps disease has been found to be clearly associated with aseptic meningitis. Mumps virus (both wild-type and vaccine strains) has been isolated from the CSF of patients with aseptic meningitis.

Case Reports, Case Series, and Uncontrolled Observational Studies

The ability to isolate mumps virus from the CSF of patients presenting with symptoms of meningitis and to determine the type of the isolate as a wild-type or a vaccine strain indicates that mumps vaccine can cause aseptic meningitis. Many case series and observational studies have documented cases of meningitis after vaccination with mumps virus-containing vaccine. Of particular interest are the cases in which the vaccine strain was identified. This has been done extensively with the Urabe strain. Data concerning the Urabe strain mumps vaccine will be presented first. Data related to the Jeryl Lynn strain (that used in the United States) are presented last.

In 1989, Gray and Bums published two letters (Gray and Bums, 1989a,b) in The Lancet concerning a 3-year-old girl presenting with aseptic meningitis 21 days after vaccination with MMR. Fluorescent-antibody tests identified the isolated virus as mumps virus (Gray and Bums, 1989a), and soon thereafter, this virus was identified by nucleotide sequencing analysis as the Urabe strain (Gray and Burns, 1989b).

Identification of the mumps virus as the Urabe vaccine strain by nucleotide sequence analysis of the isolates from eight patients with meningitis in Canada led to suspension of the sale of that vaccine in Canada in May 1990 (Brown et al., 1991). Using the polymerase chain reaction to amplify the genetic signal, investigators from Japan also typed mumps virus isolated from patients with meningitis as a vaccine strain, most probably Urabe (Mori et al., 1991; Yamada et al., 1990).

Most recently, the Nottingham (United Kingdom) Public Health Laboratory isolated mumps virus from the CSF of eight children following administration of Urabe-containing MMR (Colville and Pugh, 1992). Seven of the isolates resembled the vaccine strain (the sample from the eighth patient could not be typed). Vaccination occurred 17 to 24 days prior to the lumbar puncture. The rate of virologically confirmed and suspected MMR-associated meningitis was calculated to be 1 case per 3,800 doses. None of the children had severe illness, and no sequelae were seen. Colville and Pugh (1992) reviewed laboratory records from an approximately 3-year period and determined that there were excess cases of lymphocytic meningitis in the group that recently received MMR compared with the incidence in



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