Implementation Adherence and Operational Challenges of Rectal Artesunate for Severe Malaria in Zambia: A Mixed-Methods Study

Rectal artesunate (RAS) is a pre-referral intervention recommended for children with suspected severe malaria in remote settings where injectable treatment is not readily available. Although clinical trials have demonstrated efficacy, less is known about the behavioural and health system factors influencing effectiveness under routine conditions. A convergent parallel mixed-methods design was used to assess implementation of Zambia's RAS intervention package across three districts: Serenje, Chama, and Mwinilunga. A retrospective case-tracking investigation of all 300 children with suspected severe malaria recorded by community health workers (CHWs) assigned to study facilities examined progression and attrition across the severe malaria care cascade. In-depth interviews and focus group discussions with caregivers, CHWs, and other stakeholders explored barriers and facilitators influencing progression. Among 300 enrolled children, early attrition occurred due to negative rapid diagnostic test results. Of 239 RDT-positive children, 218 (91.2%) received RAS. Referral completion was lower; among 261 children referred and followed up at health facilities, 209 (80.1%) were confirmed to have completed referral. Of 186 children diagnosed with severe malaria at the facility, 167 (89.8%) received both injectable artesunate and follow-on artemether-lumefantrine. Patterns of disengagement varied by district, with Serenje demonstrating the most consistent progression, Chama experiencing the largest drop-off at RAS administration, and Mwinilunga showing the lowest completion of follow-on treatment. Qualitative findings revealed strong community appreciation for RAS despite stockouts, alongside social and behavioural barriers, including gendered responsibilities, transport challenges, and confusion following symptom improvement, that discouraged referral completion. RAS can be a life-saving intervention when embedded within strong health systems and community structures. Zambia's experience underscores the need for comprehensive implementation strategies that extend beyond drug distribution to include sustained CHW training, reliable commodity supply, functional referral systems, and meaningful caregiver engagement.