Quantifying Time-Dependent Predictors for the International Spatial Spread of Highly Pathogenic Avian Influenza H5NX: Focus on Trade and Surveillance Efforts.

The multiple waves of intercontinental transmission of the highly pathogenic avian influenza (HPAI) H5Nx Gs/GD lineage since its identification in 1996 are testament to its resistance to control and prevention efforts. Knowledge of the predictors of HPAI international spread can help identify strengths as well as areas for improvement in surveillance and controlling HPAI. We used 10 years of data with quarterly granularity from the World Organization for Animal Health (WOAH), United Nations (UN), International Union for Conservation of Nature (IUCN), and genetic databases for 2.3.2.1c and 2.3.4.4b H5Nx clades, to determine the impact on international viral spread of (1) six categories of poultry commodities of legal international trade, (2) wild birds' migration, (3) five types of preventive measures, (4) resources allocated to veterinary services, and (5) geographic distance between countries. Two analytical approaches were used: a generalized linear mixed model (GLMM) for all targeted countries, based on epidemiological, trade, and bird migration data. Then, phylogeography-informed generalized linear models (GLMs) with time-dependent predictors were specified for analyzing the HPAI spread between countries with available genetic data. The main conclusions of this study are that results suggested (1) a role of poultry trade in disease spread; (2) a role of migratory birds in disease spread; (3) a strong role of proximity between countries in disease spread; (4) a protective effect for resources allocated to veterinary services; and (5) a protective effect for precautions at borders in exposed countries (protective against informal trade). Our findings show the importance of proper implementation of preventive measures, as advocated in WOAH standards. In addition, our results show the complementarity of epidemiological, trade, biological, and genetic data to trace back international H5NX spread.