Abstract

Plasmodium infection triggered profound alterations in host metabolic pathways affecting glucose metabolism, lipid 
homeostasis, amino acid catabolism, and mitochondrial function across multiple organ systems. These metabolic 
perturbations represented adaptive host responses aimed at limiting parasite replication and survival, while 
simultaneously reflecting pathological processes that contributed to disease severity and complications. 
Understanding the intricate interplay between parasite-induced metabolic reprogramming and clinical outcomes 
offered opportunities for identifying novel biomarkers and therapeutic targets. This review examined the 
mechanisms of host metabolic reprogramming during Plasmodium infection and evaluated the translational 
potential of metabolic signatures for biomarker discovery and development of host-directed therapies. A 
comprehensive analysis of metabolomic studies, mechanistic investigations, and translational research examining 
host metabolic responses to malaria across experimental models and human populations was conducted. Plasmodium 
infection induced glycolytic reprogramming, impaired oxidative phosphorylation, altered lipid metabolism, 
accelerated amino acid catabolism, and systemic inflammation-driven metabolic dysfunction. Distinct metabolic 
signatures correlated with disease severity, treatment response, and clinical outcomes, offering potential diagnostic 
and prognostic utility. Host-directed therapeutic strategies targeting metabolic pathways showed promise in 
preclinical models but required careful validation to avoid compromising protective immunity. Host metabolic 
reprogramming represented a critical determinant of malaria pathogenesis and clinical outcome, with emerging 
applications in precision diagnostics and innovative therapeutic interventions that complement conventional 
antimalarial drugs.