Therapeutic immunomodulation in dengue with hyperinflammation

Dengue causes significant morbidity and mortality globally, with up to 96 million clinical infections reported annually. Despite this burden, there are no licensed therapies. Dengue can present with different symptoms, from a mild febrile illness through to life-threatening disease, characterized by shock, bleeding and organ failure. These severe manifestations occur late in the disease, often when the virus is no longer detectable, driven by a disproportionate host inflammatory response. I plan to conduct a clinical trial in Vietnam to assess whether controlling this excessive inflammation using a safe, repurposed drug, anakinra, which blocks a key cytokine receptor (IL-1R), will improve clinical outcomes in dengue patients. Alongside, I will conduct detailed mechanistic studies on cytokine levels, vascular studies, immunology and transcriptomics. This proposal will not only provide potentially the first therapeutic for dengue, using a personalized approach, but also will provide further critical understanding of the pathophysiology leading to severe disease.