Fig. 1

Dysregulated host immune and endothelial activation as the rationale to enhance clinical trial design and identify adjunctive therapeutics for severe malaria. The host-response plays a central role in the pathogenesis and outcome of severe malaria (SM). Therefore, measuring levels of biomarkers of immune and endothelial activation, could be used both to identify patients that would benefit most from randomized control trials and as surrogate endpoints. FDA-approved drugs that protect and/or stabilize the host microvasculature and/or that are immunomodulatory could be repurposed as adjunctive therapeutics for severe malaria. These candidate therapeutics should be paired with the enhanced design of clinical trials