Day-to-Day Reactogenicity and the Healthy Vaccinee Effect of Measles-Mumps-Rubella Vaccination

Abstract

ABSTRACT.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-mumpsrubella (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. At 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°F (38.5°C; 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. Pediatrics 2000;106(5). URL: http://www.pediatrics.org/cgi/content/full/106/5/ e62; vaccine, measles, mumps, rubella, reactogenicity, adverse events, zygocity, healthy vaccinee effect.ABBREVIATIONS. MMR, measles-mumps-rubella; OR, odds ratio; VA, vaccine attributability.T he measles components 1-3 used in various measles-mumps-rubella (MMR) vaccines 4,5 have been associated with various short-term and long-term adverse events. This is also true to a lesser extent for the rubella antigen, 6,7 whereas the mumps component (particularly the Jeryl Lynn strain) is deemed virtually harmless. 8 Controlled studies on vaccine reactogenicity are rare, 9 and uncontrolled studies 10 -12 exaggerate findings because of a temporal rather than a causal association with vaccination. Very little is known about factors modifying adverse reactions. 13 We performed a randomized, double-blind, placebo-controlled, and crossover vaccination trial in twins using the MMR vaccine in widest use internationally; the early results were published shortly after the trial. 14 Here we report a thorough analysis of the day-to-day symptoms and signs in 2 age groups with or without previous measles vaccination, and we examine ...

Timely Versus Delayed Early Childhood Vaccination and Seizures

“…The time period from 1 to 14 days before vaccination was excluded to reduce the potential "healthy vaccinee effect." 29 The control period was defined as the 14-day period directly after the postvaccination risk window, and the 14-day period directly before the healthy…”

SIDS and Other Sleep-Related Infant Deaths: Expansion of Recommendations for a Safe Infant Sleeping Environment

“…326 It also has been theorized that the decreased SIDS rate immediately after vaccination was attributable to infants being healthier at time of immunization, or "the healthy vaccinee effect." 327 Recent illness would both place infants at higher risk of SIDS and make them more likely to have immunizations deferred. 328 Recent studies have attempted to control for confounding by social, maternal, birth, and infant medical history.…”

Safety of Live Viral Vaccines in Patients With Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

“…Mild adverse effects of measles-mumps-rubella (MMR) vaccination include fever, rash, and lymphadenopathy and occur in approximately 5% to 15% of vaccine recipients. 1,2 Similarly, side effects of the varicella vaccine include injection site reactions, fever, and rash, which occur in 5% to 30% of individuals. [3][4][5] Severe side effects are exceedingly rare with both vaccinations.…”