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© 2021 BioMed Central Ltd unless otherwise stated. Part of Springer Nature.

Influenza super-strains can emerge through recombination of strains from birds, pigs, and humans. However, once a new recombinant strain emerges, it is not clear whether the strain is capable of sustaining an outbreak. In certain cases, such strains have caused major influenza pandemics. Here we develop a multi-host (i.e., birds, pigs, and humans) and multi-strain model of influenza to analyze the outcome of emergent strains. In the model, pigs act as “mixing vessels” for avian and human strains and can produce super-strains from genetic recombination. We find that epidemiological outcomes are predicted by three factors: (i) contact between pigs and humans, (ii) transmissibility of the super-strain in humans, and (iii) transmissibility from pigs to humans. Specifically, outbreaks will reoccur when the super-strain infections are less frequent between humans (e.g., R 0 =1.4) but frequent from pigs to humans, and a large-scale outbreak followed by successive dampening outbreaks will occur when super-strain infections are frequent between humans (e.g., R 0 =2.3). The average time between the initial outbreak and the first resurgence varies from 41 to 82 years. We determine the largest outbreak will occur when 2.3 <R 0 < 3.8 and the highest cumulative infections occur when 0 <R 0 < 3.0 and is dependent on the frequency of pig-to-human infections for lower R0 values (0 <R 0 < 1.9). Our results provide insights on the effect of species interactions on the dynamics of influenza super-strains. Counter intuitively, epidemics may occur in humans even if the transmissibility of a super-strain is low. Surprisingly, our modeling shows strains that have generated past epidemics (e.g., H1N1) could resurge decades after they have apparently disappeared.