Severe malaria treatment with rectal artesunate and artemisinin-based combination therapy in remote settings: an...

Almost 500,000 children under 5 years die annually from severe malaria in Africa. Prompt access to effective antimalarial treatment is crucial to reduce mortality. Current clinical guidelines recommend pre-referral rectal artesunate (RAS) followed by injectable artesunate and a 3-day course of artemisinin-based combination therapy (ACT). However, adherence to this treatment algorithm is not always feasible due to many reasons. Integrated community case management (iCCM) presents a promising strategy to improve timely access to care through community health workers (CHWs). This study aims to: (i) assess the feasibility of providing rapid treatment of severe malaria with RAS to children aged 6 months-5 years by CHWs or in health facilities (HFs) without injectable artesunate; (ii) evaluate recrudescence rates in children under 5 following RAS by either ACT for whom referral was not feasible or those after referral completion; and (iii) assess the impact of upgrading iCCM services on access to the formal healthcare system, including severe malaria care.

This is an effectiveness-implementation hybrid Type 3 study. The study is being conducted in Nchelenge, Zambia and Kapolowe, Democratic Republic of Congo using phased rollout of upgraded iCCM according to national guidelines. CHWs will diagnose, treat and monitor study participants, while research assistants will visit each participant on day 14 to complete a questionnaire, conduct in-depth interviews (IDIs) as well as focus group discussions (FGDs) with caregivers of sampled study participants. Primary outcomes include: (i) time from symptom onset to treatment initiation in the participants who seek care via CHWs or HFs; (ii) 28-day PCR-corrected cure rates following RAS + ACT or RAS + injectable artesunate + ACT treatment; and (iii) the proportion of study population utilizing formal healthcare services within the preceding 6 months, including suspected severe malaria cases.

This study will provide essential evidence on the feasibility and effectiveness of community-based pre-referral treatment for severe malaria in resource-limited settings, address access barriers to injectable artesunate and facility-based care, inform policy and programmatic adaptations and guide scalable strategies to enhance timely treatment, reduce mortality and mitigate drug resistance in high-burden malaria regions.