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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
in cell cultures of chicken embryo fibroblasts (rubella virus is grown in human diploid cell culture). Egg-related antigens can be detected in measles and mumps vaccines, but in extremely small quantities (much less than in the egg-derived vaccines).
Herman and colleagues (1983) reported that two children with systemic allergic reactions to egg white protein (ovalbumin) had anaphylactic reactions to MMR. Both children had serum IgE reactive with ovalbumin-related antigens in the vaccine. They had no detectable IgE directed against the measles vaccine, although IgE directed at ovalbumin was present.
Vaccine components other than egg protein have been implicated in triggering severe allergic reactions to live attenuated virus vaccines. Previously available live attenuated virus vaccines contained small amounts of antibiotics such as penicillin and streptomycin, but currently they have only trace amounts (25 µg/ml) of neomycin sulfate. They also have trace amounts of proteins such as chick embryo tissue culture protein and human serum albumin.
Case Reports, Case Series, and Uncontrolled Observational Studies
In 1981, Van Asperen et al. reported immediate reactions following administration of live attenuated measles vaccine (Rimevax) in three children in Australia. The reactions began within 30 minutes of immunization and consisted of vomiting, fever, and a rash; two of the patients also had cyanosis.
Pollock and Morris (1983) reported that nine reactions in the 170,000 children who received measles vaccine fell into their category of ''anaphylaxis and collapse'' during a 7-year period (January 1975 through December 1981) of intensified voluntary reporting of vaccine reactions in the North West Thames region of England. Some were felt to be vasovagal reactions, and some included slight facial swelling or pallor. It was unclear whether any of these reactions were anaphylactic.
Fifteen reports of reactions occurring within 30 minutes of vaccination with live attenuated measles virus (Rimevax) were received by the Adverse Drug Reactions Advisory Committee in Australia for the period February 1980 to March 1982 (McEwen, 1983). The most common findings were vomiting, changes in skin coloring, and disturbances of breathing. The mechanism of the reactions was unknown. Insufficient detail was provided to determine whether any of these reactions represented anaphylaxis. All individuals survived, and in 10 individuals the symptoms resolved without active treatment. The authors noted that the role that therapy played in the recovery of the other five children could not be assessed.
In a report from India (Sokhey, 1991), measles vaccine was involved in five incidents of adverse reactions in children. In three incidents, symp-