High cumulative viral titers of influenza virus in animals with significant disease fatality rates indicate a potential trade-off between fatality and transmissibility

Evaluating the trade-off hypothesis for the evolution of virulence using empirical data poses significant challenges. The hypothesis suggests that pathogens evolve to maximize transmissibility, but fatality imposes limits as there are diminishing gains in transmissibility. In this study, we analyzed a secondary dataset of influenza virus infections in ferrets (Mustela putorius furo), categorized by Hemagglutinin (HA) and Neuraminidase (NA) subtypes. Subgroups defined by the H7/N9 and H7/N7 combinations exhibited fatality rates of approximately 30% and reached cumulative viral titers close to 7.5 (log10 titer/mL). These levels represent intermediate fatality rates, as the H5/N6 and H5/N1 subgroups had higher fatality rates but reached lower cumulative viral titers. Using cumulative viral titer as a proxy for potential secondary transmissions, the analysis suggests that intermediate fatality rates are associated with higher numbers of secondary transmissions. However, there are significant uncertainties in subgroups with lower or no fatalities. Additionally, subgroups without fatalities showed substantial variability in cumulative viral titers.