Essential Trace Elements and Their Impact on Immune Response and Disease Severity in Malaria Infection: A Systematic Review.

Malaria remains a major global health challenge, profoundly influencing host nutritional and immune status. Essential trace elements such as iron, zinc, copper and magnesium play pivotal roles in immune regulation, antioxidant defence, and pathogen control. However, their alterations during malaria infection and implications for disease outcome have been inconsistently reported. This systematic review aimed to synthesise current evidence on serum and plasma concentrations of key trace elements in malaria-infected individuals and experimental models, and to evaluate their relationship with immune responses, disease severity, and treatment outcomes. A systematic search was conducted in various academic databases, including PubMed, Web of Science, Scopus, and Google Scholar for studies published from January 2010 to November 2025. The quality assessment of the studies was done using the Critical Appraisal Skills Programme (CASP) tool. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to ensure a comprehensive and transparent process. Across human and experimental studies, malaria infection was consistently associated with reduced serum concentrations of iron, zinc, and magnesium, while copper levels showed variable trends, often elevated in acute infection, reflecting an inflammatory response. These alterations were linked to dysregulated cytokine production, particularly increased TNF-α and IL-10, higher parasitemia, and worsened clinical outcomes. Zinc supplementation improved micronutrient status but showed limited impact on malaria incidence. Emerging spectrometric approaches demonstrated utility in trace element profiling for malaria diagnosis and prognosis. Malaria-induced disturbances in trace element homeostasis, notably reduced iron, zinc, and magnesium, and altered copper levels, contribute to immune dysfunction and oxidative stress, aggravating disease severity. Integrating targeted micronutrient interventions with antimalarial therapy may enhance host immune competence and improve treatment outcomes.