Figure 9. Pathologic events in malaria lead to radical oxygen species (ROS) generation and inflammation.

Plasmodium falciparum infection is associated with coagulation and complement activation, cytokine release, host response to infection, and activation of different cells types, including endothelial cells, platelets, dendritic cells and monocytes, and neutrophils. It is also associated with release of Pf-GPI, iron overload, heme release and Fenton reaction, and diminished levels of antioxidants [1]–[9]. Superoxide contributes to platelet aggregation, tissue factor expression, cytokine release, NF-κB activation, DNA damage, NET formation, recruitment of inflammatory cells, conversion of nitric oxide (NO) to peroxynitrate (ONOO⁻) which in turn leads to DNA damage, PARP activation, lipid peroxidation, and protein nitration. These events result in sustained inflammation [52]–[56]. NO, nitric oxide; O₂ ⁻, superoxide; ONOO⁻, peroxynitrate.