Randomized controlled trial of the effect of regular paracetamol on influenza infection

Jefferies, Sarah; Braithwaite, Irene; Walker, Steven; Weatherall, Mark; Jennings, Lance; Luck, Michelle; Barrett, Kevin; Siebers, Robert; Blackmore, Timothy; Beasley, Richard; Perrin, Kyle

There are a number of potential mechanisms by which treatment with anti-pyretics such as paracetamol may influence outcomes in influenza infection. Temperatures within the human febrile range enhance the activity of cytotoxic T lymphocytes and cytokines such as interferon (IFN). 14, 15 Paracetamol inhibits polymorphonuclear leucocyte function in vitro 16, 17 with this effect augmented at human febrile temperatures. 18 Prophylactic paracetamol at the time of vaccination impairs the humoral immune response and opsonophagocytic activity in infants, apparently independent of an effect on fever. 19 Human-tropic influenza viruses replicate in the upper respiratory tract at 33-37°C. Most naturally occurring influenza A strains that infect humans are temperature sensitive, with inhibition of replication at temperatures within the physiological febrile range of 38-41°C. 20, 21 The degree of temperature sensitivity is one of the characteristics that determine virulence. 22 This trial investigates the effects of paracetamol on viral shedding and clinical symptoms in adults with community-acquired influenza infection. We hypothesized that regular administration of paracetamol during confirmed influenza infection is associated with prolonged viral shedding, worse symptoms, and prolonged illness duration.