Artemisinin-Based Combination Therapies vs Monotherapy: Resistance Prevention in Plasmodium falciparum Malaria
Namukasa Mugerwa F.
Faculty of Medicine Kampala International University Uganda
ABSTRACT
Artemisinin resistance in Plasmodium falciparum posed a critical threat to global malaria control, with delayed parasite clearance and treatment failures increasingly reported across endemic regions. This review evaluated the biochemical rationale and clinical evidence supporting artemisinin-based combination therapies (ACTs) over monotherapy for preventing resistance emergence. A systematic literature review was conducted using PubMed, Cochrane Library, and WHO databases from 2015-2025, focusing on clinical trials, molecular surveillance studies, and mechanistic research. ACTs demonstrated superior efficacy in preventing resistance through complementary pharmacokinetic profiles that reduced selection pressure on artemisinin derivatives. PfKelch13 mutations remained the primary molecular marker for artemisinin resistance, with C580Y and other validated mutations showing strong correlation with delayed clearance phenotypes. Clinical evidence from Southeast Asia and sub-Saharan Africa confirmed that ACT deployment significantly reduced treatment failure rates compared to artemisinin monotherapy, with combination therapy providing protection factors ranging from 10-100 fold against resistance selection. Molecular surveillance demonstrated that regions with high ACT coverage maintain lower frequencies of kelch13 mutations. ACTs represented the most effective strategy for preserving artemisinin efficacy, though emerging partner drug resistance and suboptimal implementation threaten long-term sustainability. Enhanced surveillance, improved diagnostics, and next-generation combination regimens are essential for maintaining therapeutic effectiveness.
Keywords: Artemisinin resistance, Plasmodium falciparum, PfKelch13, Malaria treatment, Drug resistance surveillance.
CITE AS: Namukasa Mugerwa F. (2026). Artemisinin-Based Combination Therapies vs Monotherapy: Resistance Prevention in Plasmodium falciparum Malaria. IDOSR JOURNAL OF BIOCHEMISTRY, BIOTECHNOLOGY AND ALLIED FIELDS 11(1):116-122. https://doi.org/10.59298/IDOSR/JBBAF/2026/102116122