Age: 1.42
Sex: M
Vaccine: MEN
Symptoms: Tonsillitis, Tremor, Unresponsive to stimuli
Clinical narrative: Initial solicited report received on 04 February 2019 from an investigator participating in the below-mentioned study. This case involves a 17-month-old male subject who had febrile convulsion during the study participation. The subject's medical history and concomitant therapies were not reported. On 01 February 2019, 23 hours (elapsed time from last administration) after receiving a first intramuscular dose of blinded therapy in the right thigh (Dose Number: 9542071) on 01 February 2019, the subject had febrile convulsion. The event appeared after visit 01. The subject weight was 10.6 kg and height was 80 cm. The investigational product was received on 31 January 2019. High fever noted on 01 February 2019 at home of 106.9 temporally. In the car, the child began shaking briefly for 15 seconds and became limp and unresponsive. At ED flu test was negative. Follow up visit scheduled and the subject was sent home. The subject was seen on 03 February 2019 for a follow up for the febrile convulsions. The subject was diagnosed with acute right otitis media and acute tonsillitis. Maximum Temperature was reported as 41.61 Degree c. According to investigator the event was considered as other medically important event. It was not a MAAE event and an AESI event. Maximum intensity was reported as Grade 03. The lab data was not reported. Corrective treatment was not reported. The event febrile convulsion was resolved on 01 February 2019. Rationale for Final Investigator Causality as probable relationship to IP with seizure threshold in child with concomitant viral illness. According to the investigator, the event was related to the study vaccine or trial procedures.  Relationship to investigational product according to company: reportable. The serious adverse event did not lead to the termination of the subject from the study. Based on the information received on 04 February 2019, the study code has been broken for regulatory purposes, since the event febrile convulsion is unexpected according to reference safety information in force at time of the event onset. List of documents held by sender: none. Addendum: Upon internal review this case was amended on 11 February 2019 to update listedness to 'unlisted' from 'unknown'. CSD was taken as 04 February 2019. Follow up information received on 08 February 2019. Subject height was updated (previously reported as 80.6 cm) Elapsed time from last administration was updated; Sender's Comments: Follow up information received on 08 February 2019: This case involves a 17-month-old male study participant, who reportedly developed febrile convulsions the day after (23 hours after) receiving either the investigational MenACYW conjugate vaccine or the comparator MENACTRA vaccine. Febrile convulsions are particularly common in toddlers.  Toddlers may have a fever after receiving any vaccine, and in some toddlers, fever may lead to convulsion (febrile convulsion). In this report, the seizure was not witnessed by a health professional, and no information was available regarding any additional neurological or seizure workup, including electroencephalogram, head computed tomography scan and lumbar puncture, although it is not warranted in typical febrile convulsion. It was also not reported whether the subject had any prior personal or family history of convulsions or febrile convulsions. Importantly, this case is confounded by coincidental  acute otitis media of the right ear and acute tonsillitis, which provide an alternative infectious cause, unrelated to vaccination, for the reported event. The Investigator considered the event related to vaccination with the following rationale: "Probable relationship to IP with seizure threshold in child with concomitant viral illness." In the opinion of the Sponsor, causality in this case is indeterminate. While temporal relationship is consistent with causal association to either vaccine, and febrile convulsion has been reported with association to immunization in infants and toddlers in general, both concomitant diagnoses of acute otitis media and acute tonsillitis provide a reasonable alternative etiological explanation (i.e. coincidental infection) for the reported event.