Abstract

BackgroundInfluenza 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.MethodsHere 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.ResultsWe 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., R0=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., R0=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 <R0 < 3.8 and the highest cumulative infections occur when 0 <R0 < 3.0 and is dependent on the frequency of pig-to-human infections for lower R0 values (0 <R0 < 1.9).ConclusionsOur 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.

Highlights

  • Influenza super-strains can emerge through recombination of strains from birds, pigs, and humans

  • An initial pre-epidemic period occurs before the super-strain emerges in humans, during which the avian and human strains can cocirculate in pigs for many years or even decades before a super-strain emerges in humans (Figs. 2A-D)

  • After a super-strain has emerged in humans, there are three possible epidemiological outcomes: periodic outbreaks (Figs. 2A-B for approx. gp > 0.15); a super-strain that sustains at low levels without causing a significant outbreak (Figs. 2A-B for approx. gp < 0.15); or a strong initial epidemic followed by weaker epidemics (Figs. 2C-D), where the super-strain replaces a previously circulating strain

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Summary

Introduction

Influenza super-strains can emerge through recombination of strains from birds, pigs, and humans. 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. Influenza pandemics occur when a transmissible strain emerges into the human population in which humans have little or no immunity. Two strains may interact and recombine to form a new reassortant strain Intermediate hosts, such as pigs and domestic poultry, play an important role in influenza infection between birds and human. It has been reported that pigs are capable of infecting humans [4,10,11] and are likely candidates as intermediate hosts for coinfection of interspecies strains [12]

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