A/goose/Guangdong/1/96-like (GsGd) highly pathogenic avian influenza (HPAI) H5 viruses cause severe outbreaks in poultry when introduced. Since emergence in 1996, control measures in most countries have suppressed local GsGd transmission following introductions, making persistent transmission in domestic birds rare. However, geographical expansion of clade 2.3.4.4 sublineages has raised concern about establishment of endemic circulation, while mechanistic drivers leading to endemicity remain unknown. We reconstructed the evolutionary history of GsGd sublineage, clade 2.3.4.4c, in Taiwan using a time-heterogeneous rate phylogeographic model. During Taiwan’s initial epidemic wave (January 2015 - August 2016), we inferred that localised outbreaks had multiple origins from rapid spread between counties/cities nationwide. Subsequently, outbreaks predominantly originated from a single county, Yunlin, where persistent transmission harbours the trunk viruses of the sublineage. Endemic hotspots determined by phylogeographic reconstruction largely predicted the locations of re-emerging outbreaks in Yunlin. The transition to endemicity involved a shift to chicken-dominant circulation, following the initial bidirectional spread between chicken and domestic waterfowl. Our results suggest that following their emergence in Taiwan, source-sink dynamics from a single county have maintained GsGd endemicity, pointing to where control efforts should be targeted to eliminate the disease.

The authors have declared no competing interest.

The work was supported by the UK Research and Innovation Global effort on COVID-19 (MR/V035444/1), Wellcome (207569/Z/17/Z, 224520/Z/21/Z), the UK Medical Research Council New Investigator Research Grant (MR/X002047/1) and a University of Glasgow Lord Kelvin/Adam Smith Fellowship to KB.

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The custom codes used in analyses, and the XML files required for BEAST can be found at https://github.com/yaotli/endemic. The accession numbers of the Taiwan sequences analysed in our study are listed in Supplementary Table 2.