Age: 1.0
Sex: U
Vaccine: MMR, VARCEL
Symptoms: Kawasaki's disease
Clinical narrative: Information has been received from the authors in a published article. Background and objectives: All measles-containing vaccines are associated with several types of adverse events, including seizure, fever, and immune thrombocytopenia purpura (ITP). Because the MMRV vaccine compared with the separate MMR and MMR + V vaccine increases a toddler's risk for febrile seizures, we investigated whether MMRV is riskier than MMR + V and whether either vaccine elevates the risk for additional safety outcomes. Methods: This was a cohort study that included children aged 12 to 23 months who were members of 8 Vaccine Safety Datalink (VSD) sites from January 2000 through June 2012 and who received PROQUAD (Merck) or separately administered, same-day M-M-R II + VARIVAX (Merck) vaccines. Nine study outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis, meningitis encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was estimated by using stratified exact binomial tests. Secondary analyses examined post-MMRV or MMR + V risk versus comparison intervals; risk and comparison intervals were then contrasted for MMRV versus MMR+V. Results: A total of 123 200 MMRV doses and 584 987 MMR + V doses administered to children 12 to 23 months old from 2000 to 2012 were evaluated. Overall, rates for the 7 main outcomes during postvaccination risk intervals were low, with several outcomes having few or zero events in the risk interval after either vaccine. Estimated risk differences between MMRV and MMR + V were not statistically significant for any of the 7 main outcomes, although it was for seizure, comparing MMRV with MMR + V, the risk difference that can be ruled out with 95% confidence ranged from 0.5 case (Kawasaki disease, days 1-28) to 35 cases (ataxia, days 1-42) per 100 000 MMRV doses. In the primary analysis, there was no statistically significant difference in risk between MMRV and MMR + V during either the focal or broad risk interval for the 7 main outcomes. Analyses of seizures after October 2008 confirmed that MMRV, compared with MMR + V, was associated with a twofold increased risk 7 to 10 days after vaccination. Secondary analyses comparing risk versus comparison intervals after MMRV or MMR + V revealed an increased risk of ITP and a decreased risk of ataxia after both vaccines. Analyses also detected an increased risk for anaphylaxis after MMRV. This result was based on only 2 cases, neither of which was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions. Similar to the primary analysis, there were no significant differences in risk for the 7 main outcomes during any risk interval comparing MMRV with MMR + V. After MMR + V, the risk of ataxia was significantly lower during the risk interval. For the remaining outcomes, risk differences that can be ruled out with 95% confidence ranged from 0.08 case (arthritis) to 11 cases (ITP II, days 1-42) per 100 000 MMR + V doses. Similarly, ataxia risk was significantly lower after MMRV. For the remaining outcomes, we could rule out risk differences that ranged from 0.5 case (Kawasaki disease, days 1-28) to 10 cases (ITP I, days 1-42) per 100 000 MMRV doses. Case-centered analyses demonstrated a significantly increased risk of seizure and fever 7 to 10 days after both MMRV and MMR + V and confirmed that MMRV, compared with MMR + V, was associated with a significantly higher risk for seizure and fever 7 to 10 days after vaccination. Conclusions: This study did not identify any new safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study provides reassurance that these outcomes are unlikely after either vaccine. This report refers to 2 patients aged 12 to 23 months of unknown gender who enrolled in this study. Patients' concurrent conditions, concomitant medication and medical history were not provided. On unknown dates, the patients were vaccinated with M-M-R II (lot#, expiry date, dose, route were unspecified) and same-day VARIVAX (Merck) (lot#, expiry date, dose, route were unspecified). On unknown dates the patients experienced Kawasaki disease. The outcome of the event was not provided. The reporter considered Kawasaki disease to be related to M-M-R II and VARIVAX (Merck). Upon internal review, Kawasaki disease was determined to be medically significant. This is one of several reports from the same literature. Additional information has been requested.