While the unpredictable nature of the illness and inconsistent records have made it difficult to know for sure, the U.S. Centers for Disease Control and Prevention estimate that influenza is responsible for anywhere from around 3,000 to 49,000 deaths each year.
Worldwide, flu epidemics are thought to result in three million to five million cases of severe illness and somewhere between 250,000 and 500,000 deaths, annually.
Because strains to which humans have no prior immunity can arise suddenly—as observed with the ongoing H7N9 outbreak in China and Taiwan—preventative vaccines aren’t always an option. On top of this, antiviral-resistant strains continue to emerge, leaving physicians with few treatment choices.
In a Nature letter published today, the University of Maryland’s Stephanie Vogel and her colleagues highlight what they call “a critical need for a safe and effective therapeutic adjunct and/or alternative to influenza vaccines and antiviral agents.”
Building on their previous work showing Tlr4-/- mice are highly resistant to influenza-induced lethality, Vogel and her colleagues decided to test the therapeutic efficacy of a well-studied TLR4 antagonist in cases of acute flu infection. They chose Eritoran, the Eisai drug that recently failed to show reduced mortality in the ACCESS trial involving patients with severe sepsis.
When administered therapeutically to mice infected with a lethal flu dose, the researchers found Eritoran highly protective—leading to reduced mortality and a decrease in the severity of other clinical characteristics, such as lung pathology. Upon further study, they also found that even when treatment was initiated as many as six days post-infection, the drug still enhanced survival significantly.
“In this study, Eritoran prevented mortality when administered up to six days after influenza infection of mice,” Vogel et al., note. “This more practical timing of treatment may enable effective clinical treatment of influence and, perhaps, other infectious agents.”
While much work remains to determine whether this TLR4 antagonist is protective against flu-induced death in humans, the Maryland team notes its preclinical study shows much promise.
“Eritoran blockage of TLR signaling represents a novel therapeutic approach for inflammation associated with influences, and possibly other infections,” the authors conclude.