Host-directed therapies for malaria: possible applications and lessons from other indications

Host-directed therapies (HDT) are rapidly advancing as a new and clinically relevant strategy to treat infectious disease. The application of HDT can be broadly used to (i) inhibit host factors essential for pathogen development, including host protein kinases, (ii) control detrimental immune signalling, resulting from excessive release of cytokines, chemokines and extracellular vesicles and (iii) strengthen host defence mechanisms, such as tight junctions in the endothelium. For malaria and other eukaryotic parasite-causing diseases, HDTs could provide a novel avenue to combat the growing resistance seen across all antimicrobials and provide protection against the severe forms of disease through modulation of the host immune response.