Preliminary safety data from a randomised trial of early versus standard timing of administration of measles-rubella vaccine in Ugandan infants

Background Measles remains a major cause of child morbidity and mortality in low-resource settings. Young infants are particularly at risk of severe disease, with many lacking protective levels of maternal antibodies by six months. Vaccination before nine months in high-burden settings may confer earlier protection; however, concerns exist about its effectiveness at this age. We present early findings on enrolment, safety, and breakthrough infections following the administration of a registered measles-containing vaccine at six months versus nine months (MR1) with a subsequent booster (MR2) at 12 or 18 months of age. Methods We conducted an open-label randomised controlled non-inferiority trial at four health facilities in Kampala, Uganda. Infants aged 24–28 weeks were randomly assigned to receive MR at six and 12 months (group A), nine and 18 months (group B) or six and 18 months (group C). Infants were electronically randomised in a 1:1:1 ratio using block randomisation of varying sizes, stratified by site, maternal HIV status and baseline haemoglobin level. Caretakers recorded solicited reactions on paper diary cards, with safety-related events evaluated. Findings: 450 infants received MR1 and were enrolled. No differences in local or systemic post-vaccination events between the six and nine months MR1 groups were observed [Local: 21·2% versus 21·9% (p = 0·959), systemic: 29·2% vs 27·7% (p = 0·845)]. Most local reactions were mild and within the first four days. The majority (5/6) of hospitalisations followed common childhood illnesses, with one non-vaccine-related death six months post-MR1. Sixteen laboratory-confirmed cases of measles (10) and rubella (6), and three clinical measles cases before MR1 were registered. Most measles cases (70·0%) occurred in group C, with no measles cases registered two weeks post-MR2. Conclusion We provide further evidence on the safety of administering a measles-containing vaccine at six months of age. Trial registration: The trial was registered on 31st October 2024 with Clinicaltrials.gov with the identifier NCT06667206. Copyright: Licence CC BY