Adverse events Following Immunization with Fractional one-fifth and one-half doses of Yellow Fever Vaccine compared to full dose in children 9–23 months old in Uganda — Preliminary report

Background: In 2016, the World Health Organization recommended that a fractional dose of yellow fever vaccine could be used in persons 2 years of age or older in response to an emergency situation that resulted in a global shortage of available yellow fever vaccine. However, this recommendation did not extend to the youngest age group licensed for yellow fever vaccine as no published data were available on the use or safety of fractional dose yellow fever vaccination among children aged 9–23 months. We conducted a single-blind randomized controlled trial comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD yellow fever vaccine with full dose in children 9-23 months old in Uganda. In this paper, we present the interim analysis on safety. Methods: Children aged 9–23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data on all adverse event(s) following immunization (AEFI) during active AEFI surveillance for 28 days post-vaccination using multiple data collection tools including a home diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria. Results: Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 18 (2%) were reported to have a SAE. The most commonly reported AEFI were diarrhoea, fever and rash, each reported by 355 (34%), 338 (33%) and 188 (18%) participants, respectively. Among 18 participants with SAE, eight were reported to have seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse event among the study groups. Conclusions: Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged