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

(2025) 24:328 Cole et al. Malaria Journal https://doi.org/10.1186/s12936-025-05580-7 Malaria Journal Open Access RESEARCH 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 Andrew Cole1,2*, Timothy Chege1, Rashid Aman3, George Githuka4, Richard Muga5, Adam Aspinall6 and Gilbert Kokwaro1 Abstract 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. *Correspondence: Andrew Cole Full list of author information is available at the end of the article © The Author(s) 2025. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Cole et al. Malaria Journal (2025) 24:328 Page 2 of 16 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. Keywords Uncomplicated malaria, Multiple first-line treatment, Health systems challenges, Deployment Background Globally, an estimated 263 million malaria cases were reported in 2023, marking an increase of eleven million cases from 2022. This surge resulted in approximately 597,000 deaths, with 95% of these fatalities concentrated in twenty-nine countries. Five African nations (Nigeria, Democratic Republic of Congo, Uganda, Mozambique, and Angola) accounted for nearly half of the global cases [1]. In 2022, Kenya reported 3.5 million malaria cases and 11,788 deaths attributed to the disease [1]. Since 2000, significant declines in malaria-related morbidity and mortality have been observed across African countries, including Kenya, largely due to the widespread implementation of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and artemisinin-based combination therapy (ACT) [2]. However, malaria continues to pose a serious public health challenge on the continent. ACT is currently the first line of treatment for uncomplicated malaria in many SSA countries including Kenya. One of the challenges facing Kenya and other SSA countries is finding strategies to prolong the useful therapeutic life of current artemisinin-based combinations for uncomplicated malaria. This is because artemisinin partial resistance, manifested as increased parasite clearance time, has been reported in Southeast Asia, especially in Northeast Thailand, Cambodia and Vietnam [3–6]and some parts of SSA [7], and may soon appear in Kenya. This increased parasite clearance time has been found to be associated with Plasmodium falciparum kelch13 mutations [8]. These mutations do not appear to affect the efficacy of ACT and thus do not meet the standard definition of antimalarial drug resistance [9]. Thus, the reported increased parasite clearance times following administration of ACT has been referred to as artemisinin partial resistance [10]. Nevertheless, the increased proportion of parasites carrying the Pfkelch13 mutations in some SSA counties could be an indication that current treatment strategies and transmission dynamics give these parasites an advantage [10]. Moreover, artemisinin partial resistance places the partner drug at increased risk of malaria parasite resistance development since the partner drug is exposed to higher parasite biomass. From a broader perspective, recognizing that the spread of ACT resistance is a public health emergency and of international concern is a necessary step to coordinate an international response [3]. It threatens not only clinical management of both uncomplicated malaria and severe malaria, but al (...truncated)