Day-to-day reactogenicity and the healthy vaccinee effect of measles-mumps-rubella vaccination

Objective. Revaccination policies adopted in many countries to control measles have raised various safety issues including those concerning the second vaccine dose. We performed a prospective, double-blind, crossover trial among twins receiving a measles-mumps-rubella (MMR) vaccine. Study Design. The study comprised 1162 monozygous and heterozygous twins, each of whom randomly received placebo and then vaccine, or vice versa, 3 weeks apart, at 14 to 83 months of age. Most of the oldest children had previously been vaccinated against measles, and one half of the remainder of children had had the disease. Symptoms and signs were recorded daily on structured forms. Statistical methods included a complex analysis of the vaccine attributability of the symptoms and conditional logistic regression. Results. Vaccination-attributable events occurred in 6% overall. AL 14 to 18 months of age, reactions developed between days 6 and 14, peaking at day 10. The clearest vaccine-attributable effect was fever exceeding 101.3 degreesF (38.5 degreesC; odds ratio: 3.28; 95% confidence interval: 2.23-4.82; P < .001), but the same trend was found for rash, arthralgia, conjunctivitis, staying in bed, drowsiness, and irritability. At 6 years of age, systemic reactions occurred 5 to 15 times less frequently, only arthralgia being associated with vaccination. Zygocity, gender, history of allergy, or infections did not modify reactions. Instead, respiratory symptoms developed within days postinjection to a level of 15% to 20% without subsequent decline and with no difference between vaccinees and placebo recipients. Conclusion. Vaccination was avoided during infections, but many small children became mildly ill within a week or so with no relation to vaccination (the healthy vaccinee effect). MMR vaccine was virtually nonreactogenic when given at 6 years of age.