those who had not recently been vaccinated with MMR. More cases of Urabe strain-related meningitis have been identified in the United Kingdom, and use of the Urabe vaccine strain has been suspended in that country.
A Urabe strain-containing MMR was released in Canada in 1986. Soon after that, cases of mumps meningitis began to appear. In an investigation at Montreal Children's Hospital of four patients with meningitis that appeared within 19 to 26 days after receipt of the Urabe-containing vaccine, mumps virus was isolated from the patients' CSF, as detected by hemadsorption inhibition with mumps antisera (McDonald et al., 1989). This did not distinguish the vaccine strain from the wild-type strain; however, none of the four patients were known to have had contact with an individual with natural mumps virus infection. The illnesses were not severe, and all patients recovered without sequelae.
Retrospective studies of mumps-associated meningitis and reports from surveillance systems provide more data regarding a relation between mumps vaccine and meningitis. Cizman et al. (1989) retrospectively reviewed the medical records of 2,418 children hospitalized and treated for aseptic meningitis at University Medical Center in Ljubljana, Yugoslavia, between 1979 and 1986. The etiology of the aseptic meningitis was assessed by serologic tests and isolation of the virus from CSF, urine, feces, or throat swabs. They confirmed the presence of mumps virus strains by the complement fixation test with a specific antiserum. They also tested for poliovirus, Central European tick-borne encephalitis virus, and herpes simplex virus. In 115 children, the onset of aseptic meningitis occurred within 30 days of vaccination against measles and mumps (Leningrad 3 strain), leading to an attack rate of approximately 1 per 1,000 immunized children, as calculated by the authors. Most of the cases occurred between 11 and 25 days after vaccination. The attack rate in immunized 6- to 8-year-old children was 3.5 times greater than that in immunized 1- to 3-year-old children. None of the children had sequelae. Signs of parotitis and virologic findings suggestive of mumps infection were found in 65 of the children, although only 1 child had a history of exposure to mumps. Much more enterovirus was isolated from children with nonvaccine-associated aseptic meningitis than from the 115 children with vaccine-associated aseptic meningitis. Although the authors did not calculate a rate of aseptic meningitis and they did not report how many cases of aseptic meningitis they finally attributed specifically to mumps vaccination, they were clearly concerned about the high incidence and, on the basis of in vitro tests, believed that their vaccine was inadequately attenuated compared with the Jeryl Lynn strain.
Introduction of vaccination for measles, mumps, and rubella (using the Urabe strain mumps vaccine) in Japan in 1989 coincided with early reports of mumps vaccine-associated meningitis. This prompted surveillance efforts in Japan to study the problem. Pediatricians at 24 hospitals in the