Investigation of an outbreak of hypersensitivity-type reactions during the 2004 national measles-mumps-rubella vaccination campaign in Brazil.

Introduction: During Brazil's national measles, mumps, and rubella (MMR) vaccination campaign in August 2004, an unexpectedly high rate of hypersensitivity-type adverse events (HAEs) was reported.

Materials And Methods: We reviewed information about children with suspected HAEs reported by clinicians to Brazil's national passive surveillance system for adverse events following immunization (AEFI), compared attack rate of HAE by manufacturer of MMR vaccine used in the campaign, and conducted a case-control study to determine possible risk factors for HAEs.

Results: During the 2004 national campaign, the rate of HAEs following MMR vaccination was one log higher for manufacturer A (15.2/100,000 doses administered) compared to the other two manufacturers (1.2 and 0.6/100,000 doses; p<0.0001); a similar pattern was observed retrospectively in analysis of the 2000-2003 AEFI surveillance (0.95 vs. 0.07 per 100,000 doses administered; p<0.0001). In the case-control study, among the 49 case-patients with HAEs identified, reported symptoms included conjunctival injection (60%), urticaria (55%), fever (54%), and facial edema (53%); no deaths occurred. The median time interval between vaccination and symptom onset was 42min (range: 5min-24h). We did not identify any differences in the proportion of case-patients and control children with a history of known allergy to food (including egg, egg-containing products or gelatin), drugs, or environmental antigens.

Discussion: Our study highlights the importance of a well-functioning routine AEFI surveillance system linked with mass vaccination campaigns. Such a system in Brazil permitted timely detection of HAEs and validation of a safety signal associated with one vaccine manufacturer. Unlike earlier publications, this outbreak linked to a single manufacturer of MMR showed no association with a prior allergic history to eggs or other foods, including gelatin; subsequent studies implicate the dextran stabilizer in MMR from manufacturer A as the likely cause of HAEs.