Delivery strategies for malaria vaccination in areas with seasonal malaria transmission

**Background:** Seasonal malaria chemoprevention (SMC) is effective in preventing malaria in young children in areas with seasonal transmission, but malaria remains the most frequent cause of death and hospital admissions in children under 5 in many seasonal areas. In 2021, WHO recommended the RTS,S/AS01E malaria vaccine, including seasonal vaccination in countries with seasonal transmission. However, delivering seasonal vaccination to children up to 5 years of age requires a novel approach, as no other routine childhood vaccines follow a seasonal schedule or are routinely given beyond 2 years of age. This study aimed to identify potential delivery strategies for RTS,S/AS01E alongside SMC in Mali, assess stakeholder perceptions, and develop recommendations for implementation.

**Methods:** The study had three components. First, potential delivery strategies were identified through high-level discussions with RTS,S/AS01E plus SMC trial investigators, international and national immunization and malaria experts, and through development of a theory of change. Second, these strategies were explored through qualitative in-depth interviews with 108 participants: 25 EPI and malaria programme managers (8 national, 7 regional, 10 district), 32 health workers, 43 caregivers (17 from the trial, 26 not enrolled), and 8 community stakeholders. Interviews were conducted in French and Bambara by four trained researchers from the Malaria Research and Training Centre in Mali. A framework analysis approach was used for coding and analysis. Third, a national stakeholder workshop was held in Bamako in July 2022 with 15 participants from the National Malaria Control Programme (NMCP) and EPI to discuss findings and work toward consensus.

**Key Results:** Four delivery strategies were identified: (1) age-based vaccination via routine EPI; (2) seasonal vaccination via EPI mass vaccination campaigns (MVCs); (3) age-based priming via EPI clinics + seasonal boosters via MVCs; (4) age-based priming + seasonal boosters all via EPI clinics. Strategy 4 was developed during the study based on interview findings and expert discussions. National programme managers preferred strategy 3 (age-based EPI priming + seasonal MVC boosters) for its sustainability and high coverage potential. Regional and district programme managers and health workers preferred strategy 1 (age-based routine EPI) due to lower burden on the health system. Caregivers and community stakeholders preferred strategy 3, valuing early protection via EPI and easier access to booster doses via campaigns. At the national workshop, strategy 4 was selected as the preferred approach, primarily due to feasibility concerns with MVCs and the desire to use existing systems to reduce costs and improve sustainability. However, participants expressed concerns that the low mobilization in strategy 4 would result in poor coverage, as caregivers would need to bring children up to 5 years of age to a vaccination center every June, which is not aligned with current EPI practices. EPI coverage in Mali is estimated at 77% for DTP-3, but MCV-2 coverage is only 33%.

**Clinical Implications:** The study demonstrates that while seasonal booster doses are preferred for their efficacy (based on trial results showing benefit of a 7-dose seasonal strategy up to 5 years of age), delivering them via routine EPI rather than campaigns presents major coverage challenges. Supportive interventions including intensive communications, community health volunteer engagement, reminder systems, and defaulter tracing are likely needed. The findings are applicable beyond Mali to other countries with seasonal malaria transmission considering deployment of RTS,S/AS01E or similar vaccines like R21. Further implementation research is needed to evaluate what effective coverage is achievable via these strategies and their supportive interventions.