The five continuum of care criteria that should accompany rectal artesunate interventions: lessons learned from an implementation study in Malawi

**Background:** Rectal artesunate (RAS) is a WHO-recommended pre-referral intervention for children under 6 years with severe malaria in remote areas. However, concerns persist about the value of RAS when referral systems are weak and continuity of care cannot be guaranteed. In Malawi, Health Surveillance Assistants (HSAs) serve as the first point of care in village health clinics (VHCs) with only 12 weeks of basic training. The risk of death from severe malaria is greatest in the first 24 hours after developing danger signs, and transit time to a facility where parenteral treatment can be administered can exceed 6 hours. This study aimed to inform RAS programming using practical tools to enhance the continuum of care (CoC) from household through referral and back to recovery.

**Methods:** The study was conducted in Salima and Ntchisi districts, Malawi—moderate-to-high transmission settings in the Central Region. Malawi has a malaria incidence of 332 cases per 1000 people annually, with 82.6% of the population living in rural areas and up to 35% of children under 5 relying on VHCs as their closest point of care. The study included 23 hard-to-reach VHC zones (9 control, 14 intervention) with households located more than 5 km from a government referral facility. The intervention arm received a field-tested IEC toolkit (job aid, reference booklet, flip chart, and community posters) plus HSA sensitization training. Both arms received a dedicated carbon-copy referral slip booklet for RAS referrals. The study tracked 57 intervention and 31 control severe febrile illness (SFI) cases from VHC records for parametric analysis. Baseline and endline surveys were conducted with 173 exposed and 55 unexposed households. HSAs were contacted daily throughout the 9-month tracking phase to report actions taken during encounters with febrile children, which were triangulated with referral slips and caregiver follow-up interviews.

**Key Results:** The study identified five continuum of care criteria (5CC Framework): (1) Care transitions—80% of respondents in the exposed arm reported seeing study posters, with 92.4% able to recall key content. The VHC was the first and preferred point of care, with 80% able to reach it within 1 hour by foot. (2) Consistency of supplies—RAS was administered to 100% of cases with danger signs presenting at VHCs. Knowledge that RAS was available served as a powerful cue to seek care. However, 93% of monitoring visits revealed no on-site clinical supervision had occurred in the preceding month. (3) Comprehensiveness of care—In the exposed arm, 84.5% of cases received correct RAS dosage versus 71.9% in the unexposed arm. Children managed by sensitized HSAs with access to the job aid had significantly higher chances of receiving comprehensive care (assess–treat–refer). The odds of correct services increased with decreasing age of the child (odds ratio 0.95, CI: 0.92–0.98). (4) Connectivity of care—Referral compliance exceeded 96% in both arms. In the intervention site, 89% reached the referral centre within 24 hours, and 74% reached it in less than 5 hours. Caregivers in both arms (84.4% unexposed; 94.4% exposed) reported the referral slip had a positive impact on their reception at the referral facility. Over 93% of caregivers reported rapid improvement in their child's status post-RAS. (5) Communication—Despite high referral completion, only 24.5% of caregivers reported their child was admitted as an inpatient, and only 30% reported receiving parenteral treatment at the referral facility—indicating a major gap in post-RAS care.

**Clinical Implications:** RAS cannot operate within a vacuum. The study demonstrates that investments upstream at the VHC level (danger sign assessment, pre-referral treatment, effective referral) can be lost downstream if referred children are not admitted and treated according to severe malaria guidelines at referral centres. The 5CC Framework provides a structure for future RAS practice guidelines. Key recommendations include: RAS should only be administered by CHWs with access to referral slips; referral slips should be treated as essential commodities that must always be in stock; referral centre health workers need training on managing children post-RAS who may no longer show acute danger signs; and formal two-way referral mechanisms with feedback loops are essential. The study limitations include the use of referral slips as standard of care in both arms (not as an intervention), focus on only the VHC tier, introduction of a malaria vaccine trial in the control district, and reliance on caregiver recall for post-referral care data.