H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused transboundary epizootics in poultry and wild birds. In 2016, the H5N6 subtype of clade 2.3.4.4e HPAIVs caused multiple outbreaks in Asia, including China, Japan, Korea, and Vietnam. However, the geographical spread pattern of 2.3.4.4e H5N6 HPAIV has not been clearly identified. To better understand the emergence and transmission history of 2.3.4.4e H5N6 HPAIV, we investigated the underlying epidemiologic processes associated with this viral spread by performing a Bayesian phylogeography analysis. The results revealed that wild waterfowl played a central role in the transboundary spread of clade 2.3.4.4e H5N6 HPAIV into both endemic and non-endemic countries, causing multiple incursions of the 2.3.4.4e H5N6 HPAIV into South Korea, Japan, and Vietnam. In our analysis, Guangdong province, China was estimated to be the most probable site where 2.3.4.4e H5N6 HPAIVs emerged prior to the transboundary transmissions. Continued genomic surveillance in both wild birds and poultry would be necessary for monitoring of HPAIV incursions. In addition, enhanced biosecurity would be key to preventing the HPAIV spread by minimizing contact between domestic poultry and wild birds.
