Age: 1.0
Sex: F
Vaccine: HEPA, MMR, PNC, VARCEL
Symptoms: Febrile convulsion
Clinical narrative: This literature report was received from a physician refers to a 12 month old female patient enrolled in a study. The patient had a complex febrile seizure on Day 0, which led to hospitalization and the mother's withdrawal of the subject from the study. Background: M-M-R II was currently the only measles-mumps-rubella (MMR) vaccine licensed. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine PRIORIX when used as a first dose among eligible children. Methods: This study was conducted at 51 centers in accordance with the guidelines. The study consisted of an active phase (immediate post-vaccination interval; Days 0-42), an extended safety follow-up phase (Days 43-180), and an antibody persistence phase ending approximately 2 years post-vaccination. Eligible healthy 12- to 15-month-old male and female subjects had not been previously immunized against (and had no previous history of) measles, mumps, rubella, varicella, and hepatitis A, and had received 3 doses of PCV7 within the first year of life (third dose administered >= 30 days before enrollment). Subjects visited the study site at Days 0, 42, 180, 365, and 730. At Day 0 (Visit 1), subjects were randomized using a blocking scheme (3:3:3:[1:1:1] ratio) to 1 of 4 parallel treatment groups: 3 groups received a single dose of 1 of 3 MMR-RIT lots (containing either high [MMR-RIT-1], medium [MMR-RIT-2], or low [MMR-RIT-3] RIT 4385 mumps strain titers); the fourth group received a single dose of 1 of 3 commercial lots of MMRII (Lot # was reported as 1291X, 1255X or 1362X) (Merck and Co Inc.). Subjects concomitantly received a single dose each of HAV (HAVRIX, GlaxoSmithKline Vaccines), VAR (VARIVAX, Merck and Co. Inc.), and PCV7 (PREVNAR, Wyeth) at Day 0. Immune response against measles, mumps, and rubella viruses was assessed at Day 42 (Visit 2). MMR-RIT or MMRII were administered subcutaneously into the upper right arm, VAR subcutaneously into the upper left arm, and HAV and PCV7 intramuscularly into the left and right thighs, respectively. A second HAV dose was administered at Day 180 (Visit 3). Vaccine recipients, parents/guardians, and those responsible for evaluation of study endpoints were blinded to study treatment. Vaccine reception, storage, preparation, reconstitution, and administration were performed by study personnel who did not participate in outcome evaluation. Incidence of solicited injection site, general, and serious adverse events was assessed. Results: The first subject was enrolled on June 3, 2009, and the last visit of the active (43-day) phase was completed on July 21, 2010. Of 1259 enrolled subjects, 1224 were randomized and 4 did not receive study vaccine. The TVC consisted of 1220 subjects: MMR-RIT-1 (n = 304), MMR-RIT-2 (n = 304), MMR-RIT-3 (n = 304), and MMRII (n = 308). Of these, 1117 completed Day 42 and 103 were withdrawn. Overall, of 1220 subjects in the TVC, 1026 subjects were included in the ATP-immunogenicity cohort (194 subjects were excluded): MMR-RIT-1 (n = 261); MMR-RIT-2 (n = 254); MMR-RIT-3 (n = 251), and MMRII (n = 260). Demographic characteristics of the 4 treatment groups were comparable between the TVC and ATP-immunogenicity cohorts. Mean (standard deviation) age in the TVC was 12.3 (0.71) months, and 51.1% were male. In the ATP-immunogenicity cohort, 100%, 86.2%, and 99.8%, of subjects were seronegative for measles, mumps and rubella antibody, respectively, before study vaccination; overall baseline seronegativity rates were comparable across the 4 groups. Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3-99.2% (measles), 89.7-90.7% (mumps), and 97.5-98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups. One MMRII recipient had a complex febrile seizure on Day 0, which led to hospitalization and the mother's withdrawal of the subject from the study; this event, classified as an SAE, was considered to be related to the study vaccine. Of 15 SAEs reported in 11 subjects (Days 0-42), 2 SAEs were considered to be related to study treatment: febrile convulsion in a 12-month-old female MMRII recipient (described above), and idiopathic thrombocytopenic purpura (onset at Day 20) in a 13-month-old female MMR-RIT-2 recipient who was hospitalized for treatment and discharged after 3 days. Both subjects with vaccine related SAEs were withdrawn from the study. All SAEs resolved without sequelae. Concomitant Medication: Rates of concomitant medication use (Days 0-42) were the following: MMR-RIT-1 (76.6%), MMR-RIT-2 (72.0%), MMR-RIT-3 (74.0%), and MMRII (70.1%). Rates of antipyretic medication use were the following: MMR-RIT-1 (65.1%), MMR-RIT-2 (59.2%), MMR-RIT-3 (64.1%), and MMRII (57.5%). Conclusions: Immune response were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. Upon internal review, complex febrile seizure was considered as medically significant. Additional information has been requested.