Conjunction of Factors Triggering Waves of 1 Seasonal Influenza

12 Using several longitudinal datasets describing putative factors affecting influenza incidence and clinical data on the disease 13 and health status of over 150 million human subjects observed over a decade, we investigated the source and the mechanistic 14 triggers of influenza epidemics. We conclude that the initiation of a pan-continental influenza wave emerges from the simulta15 neous realization of a complex set of conditions. The strongest predictor groups are as follows, ranked by importance: (1) the 16 host population’s socioand ethno-demographic properties; (2) weather variables pertaining to specific humidity, temperature, 17 and solar radiation; (3) the virus’ antigenic drift over time; (4) the host population’s land-based travel habits, and; (5) recent 18 spatio-temporal dynamics, as reflected in the influenza wave auto-correlation. The models we infer are demonstrably predictive 19 (area under the Receiver Operating Characteristic curve 80%) when tested with out-of-sample data, opening the door to the 20 potential formulation of new population-level intervention and mitigation policies. 21