Flying Over an HPAI H5N1 Infected Landscape 449 (Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl. Keywords: avian inﬂuenza, epidemiology, disease ecology, migration INTRODUCTION Since 2003, highly pathogenic avian inﬂuenza (HPAI) H5N1 has caused outbreaks in poultry and wild birds across Asia, Europe, and Africa, and persisted over several years in many countries (Liu et al., 2005; Alexander, 2007). Compared to epizootics caused by other subtypes, HPAI H5N1 showed a capacity to spread on continental and subcontinental scales. The success of the HPAI H5N1 virus, when compared to other HPAI subtypes, may result from its capacity to persist and evolve in localized areas (Li et al., 2004) and to be transmitted over long distances. Several conditions that promote long-term, local per- sistence have been identiﬁed. First, controlling HPAI H5N1 virus is difﬁcult in the presence of millions of domestic ducks in rural landscapes. Domestic ducks show fewer clinical signs of disease than chickens, and can shed virus up to 17 days (Hulse-Post et al., 2005). Vaccination-based control strate- gies are difﬁcult to implement in ducks because they have longer production cycles and lower vaccine efﬁciency (compared to chickens), requiring repeated injections throughout the animal’s life (Tian et al., 2005). Second, poor veterinary services and low bio-security measures in farms, wet markets, and along market chains are other important factors contributing to HPAI H5N1 virus persistence in South Asia (Sims, 2007). Third, even in the absence of those conditions, new introduction from endemically infected countries through regular poultry trade (Gauthier-Clerc et al., 2007), smuggling (Van Borm et al., 2005), contami- nated fomites (Yamamoto et al., 2008), or migratory birds contributes to HPAI H5N1 reintroduction and persistence (Ducatez et al., 2006; Starick et al., 2008; Globig et al., 2009). Another unique feature of HPAI H5N1 virus is the spill-over from domestic poultry to wild birds. HPAI H5N1 can be highly pathogenic to many wild bird species, for example, wild bird outbreaks in Qinghai Lake, China in May 2005 (Chen et al., 2005; Liu et al., 2005), and it can also cause subclinical infections in others (Keawcharoen et al., 2008). Several ﬁeld studies have looked at detailed migration patterns (Gaidet et al., 2008; Yamaguchi et al., 2008; Prosser et al., 2009; Takekawa et al., 2010), and experimental infection studies have examined the clinical impact and asymptomatic shedding of HPAI H5N1 for a range of species (Brown et al., 2008; Keawcharoen et al., 2008; Kwon and Swayne, 2008), which supported the hypothesis that wild waterfowl may be involved in long- distance transmission of the virus (Kalthoff et al., 2008). A hypothesis is that the global persistence of HPAI H5N1 results from the interplay between the high capacity to persist in domestic poultry in localized areas and spo- radic long-distance introduction events through migratory birds. To date, this hypothesis has never been presented with supporting and integrated empirical data. Here, we studied those two processes, i.e., persistence and long-dis- tance spread, using two approaches: (1) quantifying and mapping HPAI H5N1 risks in South Asia (India, Bangla- desh, and Myanmar) and Southeast Asia (Thailand, Cam- bodia, Laos, and Vietnam); and (2) tracking wild bird migration from regions identiﬁed at risk in South Asia through western China to Mongolia and Russia (Central Asia ﬂyway) by satellite telemetry. MATERIALS AND METHODS Ethics Statement Bird capture and marking was conducted under the U.S. Geological Survey (USGS) Western Ecological and Patux- ent Wildlife Research Center’s Animal Care and Use Committee Review. Epidemiological Data All data on HPAI H5N1 outbreaks were extracted from the EMPRES-I database maintained by the Food and Agricul- ture Organization of the United Nations, except data on HPAI H5N1 outbreaks prior to December 2005 in Thailand and Vietnam that originated from the Thailand Department of Livestock Development (DLD, Bangkok, Thailand) and the Vietnam Department of Animal Health (DAH, Hanoi, Vietnam), respectively. Table S1 presents the sources of poultry data used in the region to derive the layers of chicken