Adverse events following immunization (AEFI) with fractional one-fifth and one-half doses of yellow fever vaccine compared to standard dose in children 9-23 months old in Uganda, 2019-2022 - final report.

BACKGROUND

Lacking adequate safety data, the World Health Organization (WHO) recommends a full dose of yellow fever (YF) vaccine to children two years or younger. In older age groups in outbreak settings, the WHO recommends a fractional dose of YF due to vaccine shortages. Therefore, in children aged 9-23 months, we conducted a single-blind randomized controlled trial to compare the safety of fractional 1/2 and 1/5 doses of BioManguinhos 17DD YF vaccine with the full dose. This paper presents the final safety analysis for this trial.

METHODS

At three study sites in Uganda, healthy children aged 9-23 months were recruited for inclusion. Data on adverse events following immunization (AEFI) was collected from March 26, 2019, to December 30, 2022, using active surveillance for 28 days post-vaccination. A diary card and a thermometer were used for the first 14 days post-vaccination. Serious adverse events (SAE) were investigated by an independent team from the Uganda AEFI committee.

RESULTS

1066 (60 %) of 1770 enrolled children reported at least one non-serious adverse event (NSAE), with the most reported events being fever 610 (34 %) and diarrhea 608 (34 %). Fever and diarrhea prevalence both peaked two days post-vaccination, and fever prevalence was statistically higher in the full dose group than either fractional dose group. Thirty (1.7 %) of participants reported a SAE, with no difference by study arm; this included three SAEs reported to be vaccine product-related by the causality committee. Although six deaths occurred during the study, none were causally associated with the vaccine.

CONCLUSIONS

Our study did not identify any unexpected safety issues with the YF fractional or full dose vaccine and Vaccine-related SAEs were rare. Although our study was not powered to identify associations for the safety outcomes monitored, our findings provide further evidence on the safety of YF fractional dosing in children aged 9-23 months (NCT03725618).