Adverse events associated with MMR vaccines in Japan

Abstract

The largest nationwide active surveillance of four Measles‐Mumps‐Rubella (MMR) vaccines was conducted in Japan. A total of 1255 pediatricians actively participated in the study, which comprised 8.6% of all members of the Japanese Pediatric Society. The total number of registered recipients of MMR vaccines was 38 203. They were arbitrarily given one of the MMR vaccines produced by three makers (Takeda, Osaka city, Kitasato Minato‐ku, Tokyo and Biken Suita city, Japan) or the standard MMR vaccine made of designated strains (Kitasato's measles‐AIK‐C, Biken's mumps‐Urabe Am9 and Takeda's rubella‐To336) produced by Takeda, Kitasato and Biken and were observed for 35 days. The rates of virologically confirmed aseptic meningitis per 10 000 recipients were 16.6, 11.6, 3.2 and 0 for the standard MMR, Takeda MMR, Kitasato MMR and Biken MMR vaccines, respectively. The incidence of convulsions between 15 and 35 days was the highest with the standard MMR vaccine and the incidence of fever associated with vomiting occurring between 15 and 35 days (symptoms relevant to aseptic meningitis) were also the highest with the standard MMR vaccine. The incidence of parotid swelling was the lowest with Takeda MMR vaccine. This surveillance revealed that incidences of aseptic meningitis after administration of the standard MMR vaccine and of Biken MMR vaccine were different. This posed questions about the manufacturing consistency of the Urabe Am9 mumps virus vaccines. On the other hand, the National Institute of Health found that the biological characteristics of the Urabe Am9 mumps virus contained in the standard MMR vaccine and in the Biken MMR vaccine were different. The Biken Company reported that the mumps vaccine in the standard MMR vaccine was a mixture of two Urabe Am9 mumps vaccine bulks; one identical to that contained in the Biken MMR vaccine and the other produced by a different manufacturing process.

Rapid Diagnostic Method for Detection of Mumps Virus Genome by Loop-Mediated Isothermal Amplification

“…A lower virus load was noted for those who had been immunized before, and we speculated that the remaining immunity modified virus growth even though SVF occurred. Among recipients with the Hoshino mumps vaccine strain, approximately 2 to 3% developed parotitis 2 to 3 weeks after vaccination (9). Although the symptoms for vaccine-associated parotitis were mild without febrile illness in comparison with natural primary infection, no significant difference in viral load was observed in patients with vaccine-associated acute parotitis or natural primary infection.…”

Mumps virus reinfection is not a rare event confirmed by reverse transcription loop‐mediated isothermal amplification

“…Especially, more than 56,390 patients were reported in the UK during 2004-2005[CDC, 2006a, as well as multi-state outbreaks in the US [CDC, 2006b,c], and in several countries [Utz et al, 2004;Donaghy et al, 2005;Š antak et al, 2006]. In Japan, MMR vaccine was administered between 1989 and 1993, but discontinued because of an unexpectedly high incidence of aseptic meningitis [Ueda et al, 1995;Kimura et al, 1996]. Since 1993, a monovalent mumps vaccine has been used but vaccine coverage is estimated to be less than 30% [Nagai et al, 2007].…”

Studies on the Association of Meningitis and Mumps Virus Vaccination

“…Reports of meningitis in patients immunized with Urabe AM9 strain range from 1/233,000 to 16.6/10,000 administered doses (Kimura et al, 1996;Schmitt et al, 1993). An outbreak of aseptic meningitis following the mass immunization campaign with an Urabe-containing vaccine was reported, with an estimated risk of aseptic meningitis 1 per 14,000 doses.…”