Studies on Influenza Virus Transmission between Ferrets: the Public Health Risks Revisited

Fouchier, Ron A. M.

In previous work (1) (2) (3) (4) , it was assumed that if a ferret-adapted avian influenza virus caused an LAI and onward transmission, it could cause a pandemic with an attack rate of 24 to 38%, as deduced from previous pandemics, and a case fatality rate ranging from 1 to 60% in a population of 7 billion people, thus leading to millions of, or more than a billion, fatalities. However, I consider an attack rate and case fatality rate of this magnitude to be unrealistic. Given that the avian influenza viruses under investigation are ferret adapted rather than human adapted, it is unlikely that these viruses would spread as efficiently between humans. Of note, this does not mean that the ferret model is therefore useless for studies to increase our fundamental knowledge about airborne virus transmission; it simply means that-just like when the mouse model is used to address fundamentals in immunology-we need to carefully validate any results obtained in animals before extrapolation to humans. Throughout the history of virology, scientists have adapted viruses to cells, chicken embryos, or animal species in order to yield viruses that have increased replication properties in these specific hosts or cells but at the same time lose replication capacity and virulence in others (27) . Examples are the passaging of vaccinia virus in chicken embryo fibroblasts to yield modified vaccinia virus Ankara (MVA), which is now in use as a safe vaccine vector (28) , the passaging of measles virus, mumps virus, and rubella virus in various cells to yield the live-attenuated MMR vaccine (29) , and the passaging of influenza viruses in mice, ferrets, and eggs to yield the vaccine strain A/PR/ 8/34 (30) , all of which are highly attenuated in humans.