Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been first-line treatment for uncomplicated malaria in sub-Saharan Africa for over two decades. However, emerging artemisinin partial resistance threatens efficacy. Multiple first-line treatments (MFTs) represent a proposed mitigation strategy, though associated health systems challenges remain unknown. This study evaluated health systems challenges and facilitators for MFT implementation in western Kenya. METHODS: A 2 year pilot study (June 2020-June 2022) implemented adaptive cycling of four artemisinin-based combinations: Artemether-Lumefantrine (AL), Dihydroartemisin-Piperaquine (DHA-PIP), Amodiaquine-Artesunate (ASAQ), and Pyronaridine-Artesunate (PYR-ART) in western Kenya. Homa Bay (implementation) and Migori (control) counties were compared. Implementation involved 8 month drug cycling on mainland and 12 month cycling on Mfangano Island, while control county continued AL throughout. Adult patients diagnosed with uncomplicated malaria were included (pregnant women and children < 5 years excluded). Health systems assessment used semi-structured questionnaires, key informant interviews, and exit interviews. Outcome measures included diagnostic kit availability, procurement logistics, information system alignment, human resources, stakeholder acceptance, and side effects. Costs were tracked using ingredient approach, and malaria cases compared between counties. RESULTS: MFT was accepted by key stakeholders. One minor adverse effect (vomiting) was reported. Patients preferred simple once-daily dosing of new drugs over AL's complicated regimen. Major challenges included logistics inefficiencies in drug quantification and stock management, human resource constraints, information system reconfiguration needs, and frequent diagnostic kit stock-outs. Start-up and implementation costs were roughly equal. Economic cost per patient treated was USD 3, lower than reported elsewhere in sub-Saharan Africa. Digital health tools (SMS/WhatsApp) facilitated implementation through improved communication and follow-up. Migori (control) showed 12.5 percentage points higher malaria positivity rates (23.3% vs 10.8%) with better directional consistency. Testing efficiency differed markedly (4.3 vs 9.2 tests per positive case) between counties. CONCLUSION: Adaptive cycling MFT implementation is feasible in Kenya with adequate planning and addressing health systems challenges. Stakeholder engagement and continuous training were critical for success. Policy implications and regional cooperation potential warrant exploration in other sub-Saharan African countries with different deployment contexts.