The 2014 – 2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models modified to incorporate epidemiological and geographic information. Epidemiological compartmental models constructed in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, a continuous external source of virus was not needed to explain the propagation of HPAI cases within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance, road density and proportion of water coverage were all supported as associated with viral transition between county groups (Bayes Factor > 3.0). Together these findings indicate that the midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry sectors and geographic factors.


AUTHOR SUMMARY The highly pathogenic avian influenza outbreak among poultry farms in the midwestern United States appears to be influenced by agricultural and geographic factors. After initial introduction of the virus into the poultry industries, no further introductions (such as from a wild bird reservoir) were necessary to explain the continuation of the outbreak from March to June 2015. Additionally, evidence suggests that proximity increases the chances of viral movement between two locations. While many hypotheses have been proposed to explain the transmission of virus among poultry farms, the support for road density as an important driver of viral movement suggests human-mediated viral transportation played a key role in the spread of the highly pathogenic H5N2 outbreak in North America.