Clinician-initiated research on treating the host response to pandemic influenza.

To prepare for the next influenza pandemic and other emerging virus diseases, scientists and health officials are focused on developing new vaccines and treatments that target these viruses. Ideally, these interventions could be highly effective, but for many practical reasons these "top down" efforts are unlikely to provide clinicians with what they will need to manage their patients. As a "bottom up" alternative, combinations of generic drugs like statins and angiotensin receptor blockers (ARBs) might be used to treat the host response to infection. These drugs counteract endothelial dysfunction, a central abnormality in these diseases. Observational studies in patients with influenza, pneumonia, sepsis and Ebola suggest they might work. During the 1918 influenza pandemic, children were infected more frequently than adults, but their mortality rate was much lower. Their survival was probably due to better tolerance (reduced pathogen damage), not greater resistance (reduced pathogen burden). The same pattern of susceptibility characterizes other infectious diseases, and it probably reflects the heritage of human evolution. Drugs like statins and ARBs can metabolically reprogram the host response and improve tolerance to infection. Treating the host response is not on the research agendas of international agencies responsible for pandemic preparedness. Consequently, clinicians might have to undertake clinical trials in patients hospitalised with seasonal influenza, pneumonia and sepsis in order to show convincingly whether treating the host response would work. Most candidate generic drugs are inexpensive, widely available, known to be safe and used by clinicians every day. Demonstrating their efficacy would mean that patients in all countries would have access to treatment on the first pandemic or epidemic day.