Table 1. Conventional treatment, phytotherapy, and nanomedicine.

	Conventional treatment	Phytotherapy	Nanomedicine	References
Source/origin	4 major classes: •  Quinoline-related compounds (plant origin) • Antifolates, • Artemisinin derivatives (plant origin), • Two antibiotic families: macrolides and tetracyclines • Recently, Falcipain inhibitors e.g., Quinoline-4-carboxamide derivative, The (E)-chalcone inhibitor, and Tetracycline	Stem, seeds, leaves, or the roots of the medicinal plant Examples: Buchholzia coriacea, Gymnema inodorum, Anogeissus leiocarpus, Triumfetta cordifolia, Bidens pilosa, Syzygium guineense and Parinari congensis, Amaranthaceae, Annonaceae, Nyctagynaceae, Rubiaceae, Vitaceae etc.	•  Metallic NPse.g., gold and silver a. Non-biological methods (physical and chemical). b. Biological method (green NPs from bacteria, fungus, plant) •  Inorganic nonmetallic NPs a- Titanium dioxide, b- Zinc oxide, c- Cadmium oxide • Carbon-based NPs a- Multi-walled carbon nanotubes. b- Carbon–silicon	Erhirhie et al. (2021); Boonyapranai et al. (2022b); Dahiru, Badgal & Neksumi (2023); Ezenyi et al. (2020); Panneerselvam et al. (2019)
Action	• Quinoline: interacts with RBCs membrane stomatin protein • Antifolates: antagonize vit B9 (folic acid) • Artemisinin: decomposes the endoperoxide bridges of heme producing toxic anti-parasite free radicals. • Macrolides: inhibits parasite’s RBC invasion • Tetracycline: targets Plasmodium apicoplast • Falcipain inhibitors: hydrolyses hemoglobin	• Buchholzia coriacea Engl. seeds and Gymnema inodorum leaf. improves the hematological and biochemical parameters. • Anogeissus leiocarpus. Anti-oxidants improve liver functions. • Triumfetta cordifolia,Bidens pilosa, Syzygium guineense and Parinari congensis extracts. anti-plasmodial activity.	• Diffusion via RBCs membrane, • or interacts with the RBC membrane	Gaillard et al. (2016); Wilson et al. (2015); Biddau & Sheiner (2019)
Advantage	• Artesunate of choice in adult cerebral falciparum malaria • The artemether is rapidly absorbed • Artemisinin selectively toxic to parasite	• Ameliorates physiological and biochemical changes • Selective toxicity of the parasite	• Biological extraction of metal NPS is friendly to the ecosystem. • Inorganic NPs are non-toxic, hydrophilic, biocompatible, and stable compared to organic materials • Improved AUC curve. • Lower doses • Lower frequencies of administration, • Improved half-life time, • Better water solubility	• South East Asian Quinine Artesunate Malaria Trial (SEQUAMAT) group (2005); • White, van Vugt & Ezzet (1999)
Limitations	• Multi-drug resistance, • Declining efficacy, • High cost, • Toxicity, • Short half-life time, • Low water solubility • Limited as chemoprophylactic e.g., Quinine • Restricted in organ dysfunction e.g., hepatic dysfunction →impairs the conversion of quinine to 3-hydroxyquinoline.	• Parasiticidal efficacy needs further research. • Systemic effects of the medicinal plant not evaluated. • Effects are dose-dependent.	• Non-biological extraction of metallic NPs is hazardous. • Limited industrial chances, • Not cost effective, • Limited clinical trials	• Baruah et al. (2018) • Shanks (2016) • Erhirhie et al. (2021)
Prospective Areas of Research	• Studies on gene mutation, • Trials of combined treatment with modified chemical formulas	• Effects of combined crude plant extracts + chemotherapy against cytokine storm of acute malaria • Phyto therapies versus chemotherapies regarding anti-inflammatory, and anti-oxidative effects using different plant species. • Evaluation of the plasmodocidal effects of various plant species in particular in complicated and resistant strains. • Refining research on a species-specific level. • Assessing its antimalaria prophylactic activity.	• The biological synthesis of metallic NPs (green NPS) • Comparative studies of Green NPs using different plant species • Assessing solid lipid NPs as a carrier or antimalaria target therapy in resistant malaria • Systemic assessment of the biological effects of NPs • Evaluation of NPs with or without drugs in complicated or acute malaria.