Vol. 7, Issue 2, Part D (2025)

Malaria remains one of the most significant parasitic diseases worldwide, with nearly 249 million cases and over 600,000 deaths reported in 2022, predominantly in sub-Saharan Africa and Southeast Asia. Despite major advances in control strategies, the emergence and spread of drug-resistant Plasmodium falciparum and Plasmodium vivax continue to threaten progress. Artemisinin-based combination therapies (ACTs) remain the cornerstone of treatment for uncomplicated malaria; however, resistance linked to kelch13 mutations and declining efficacy of partner drugs such as piperaquine and mefloquine underscore the fragility of current approaches. For P. vivax, relapse due to dormant hypnozoites presents an additional challenge, with primaquine and tafenoquine providing radical cure but limited by safety concerns in glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Recent advances in malaria therapeutics include the development of triple artemisinin combination therapies (TACTs), which combine an artemisinin derivative with two partner drugs and have shown high efficacy against multidrug-resistant strains. Novel chemical entities such as cipargamin, ganaplacide, MMV390048, artefenomel, and DSM265 are progressing through clinical trials, targeting unique parasite pathways and offering promise for overcoming existing resistance. In parallel, major breakthroughs have been achieved in vaccine development. The RTS,S/AS01 vaccine, the first malaria vaccine to be recommended for large-scale use, demonstrates modest but impactful protection, while the newer R21/Matrix-M vaccine has shown higher efficacy in phase II trials and is undergoing large-scale evaluation. Whole sporozoite vaccines and monoclonal antibodies such as CIS43LS further expand the immunological toolkit.
Innovative strategies, including long-acting injectable prophylaxis, AI-driven drug discovery, and CRISPR-based gene-drive mosquito control, represent a paradigm shift in integrated malaria management. Together, these advances mark an important turning point in the global fight against malaria. Sustained investment, equitable access, and continuous surveillance are critical to translating these innovations into meaningful progress toward elimination.