Insights into malaria pathogenesis gained from host metabolomics

Analyses can be performed on biological fluids and tissues (e.g., plasma and urine), volatile organic compounds (VOCs, e.g., odor from breath or skin), and cell cultures as either untargeted or targeted, the former outputting a vast dataset based on chemical features (e.g., mass-to-charge ratio) and the latter including chemical annotations based on reference compounds. In particular, we focus on amino acid, lipid and fatty acid, and red blood cell (RBC)-related alterations in the bloodstream of hosts during malaria infection and how this compares to other diseases. While depletion of host arginine could derive in part from parasite-specific processes (e.g., elevated Plasmodium arginase activity [19]), experiments using murine and nonhuman primate models paired with analyses of human samples have demonstrated simultaneously diminished levels of arginine and its biosynthetic pathway metabolites (e.g., ornithine and citrulline) in the blood of malaria-infected hosts [9,18,21] (Fig 1A). Red blood cell–related alterations in malaria metabolome Malaria is associated with a vast loss of RBCs due, in part, to parasite-mediated lysis, with hemoglobin and free heme being released in the process.