Three‑dose Completion of R21/matrix‑M Malaria Vaccine among Children Eligible for the Third Dose in Kole and Kwania Districts, Uganda: A Parallel Mixed‑Methods Study.

Abstract

Background: The R21/Matrix-M malaria vaccine (hereafter “R21”) contains the R21 antigen and Matrix-Madjuvant. Completion of the initial three-dose series is important for protection, but continuation through multi-dose schedules remains a programmed challenge. This study assessed three-dose completion and associated fac-tors among children who had initiated vaccination and were eligible for dose three in Kole and Kwania districts, Uganda, and explored barriers and facilitators of completion. Methods: A convergent mixed-methods was conducted from September to October 2025. A community-based cross-sectional survey included caregivers of 733 children who had received dose one at least 3 months before enrolment. Descriptive analyses and modified Poisson regression with village-clustered robust standard errors were used; adjusted prevalence ratios (aPRs) and 95% confidence intervals were reported. Qualitative data were collected from 55 participants through key informant interviews, caregiver in-depth interviews and caregiver focus group discussions using semi-structured guides. Recordings were transcribed, anonymised and analysed in ATLAS.ti 25. The components were analysed separately and integrated through a convergence matrix. Results: Of the 733 children, 399 (54.4%) were female and 404 (55.1%) were aged ≤12 months. Three-dose completion was 55.7% (village-clustered 95% CI: 48.6–62.7). Among the 408 children who completed three doses, 360 (88.2%) received the third dose within the specified timing window. In the adjusted analysis of 727 children, caregiver-reported vaccine unavailability was associated with lower completion (aPR 0.64, 95% CI: 0.44–0.93). Health-worker reminders were not significantly associated with completion (aPR 1.09), and walking time was not statistically significant overall (p = 0.074). Qualitative analysis involving 55 participants identified two overarch- ing themes: factors supporting completion, including perceived benefits, caregiver motivation, reminders, and community support; and barriers, including missed appointments, vaccine unavailability, transport difficulties, safety concerns, and gender-related responsibilities. Conclusions: Just over half of children completed the initial three-dose R21/Matrix-M series. Caregiver-reported vaccine unavailability was associated with lower completion, while qualitative findings highlighted practical barriers and sources of support. The Ministry of Health should prioritise reliable vaccine availability and evaluate outreach and reminder strategies to support completion.