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Abstract
Influenza pandemics can emerge unexpectedly and wreak global devastation. However, each of the six pandemics since 1889 emerged in the Northern Hemisphere just after the flu season, suggesting that pandemic timing may be predictable. Using a stochastic model fit to seasonal flu surveillance data from the United States, we find that seasonal flu leaves a transient wake of heterosubtypic immunity that impedes the emergence of novel flu viruses. This refractory period provides a simple explanation for not only the spring-summer timing of historical pandemics, but also early increases in pandemic severity and multiple waves of transmission. Thus, pandemic risk may be seasonal and predictable, with the accuracy of pre-pandemic and real-time risk assessments hinging on reliable seasonal influenza surveillance and precise estimates of the breadth and duration of heterosubtypic immunity.
Author summary
Influenza pandemics emerge via genomic reassortment between circulating human and animal strains. The risk of pandemic emergence should therefore be high during the flu season, when viruses are abundant and conditions favor transmission. However, the six pandemics on record since 1889 all emerged in the Northern Hemisphere following the flu season, suggesting that other forces may predictably constrain pandemic risk. We find that seasonal influenza epidemics leave a wake of immunity that impedes pandemic emergence. This transient refractory period is consistent with the spring-summer emergence, multiple wave dynamics of recent pandemics, and may cause initial underestimation of the viral transmission rate. These findings may improve pre-pandemic risk assessments and real-time situational awareness, particularly as we gain greater insight into the extent of immunity.
full article
Influenza pandemics can emerge unexpectedly and wreak global devastation. However, each of the six pandemics since 1889 emerged in the Northern Hemisphere just after the flu season, suggesting that pandemic timing may be predictable. Using a stochastic model fit to seasonal flu surveillance data from the United States, we find that seasonal flu leaves a transient wake of heterosubtypic immunity that impedes the emergence of novel flu viruses. This refractory period provides a simple explanation for not only the spring-summer timing of historical pandemics, but also early increases in pandemic severity and multiple waves of transmission. Thus, pandemic risk may be seasonal and predictable, with the accuracy of pre-pandemic and real-time risk assessments hinging on reliable seasonal influenza surveillance and precise estimates of the breadth and duration of heterosubtypic immunity.
Author summary
Influenza pandemics emerge via genomic reassortment between circulating human and animal strains. The risk of pandemic emergence should therefore be high during the flu season, when viruses are abundant and conditions favor transmission. However, the six pandemics on record since 1889 all emerged in the Northern Hemisphere following the flu season, suggesting that other forces may predictably constrain pandemic risk. We find that seasonal influenza epidemics leave a wake of immunity that impedes pandemic emergence. This transient refractory period is consistent with the spring-summer emergence, multiple wave dynamics of recent pandemics, and may cause initial underestimation of the viral transmission rate. These findings may improve pre-pandemic risk assessments and real-time situational awareness, particularly as we gain greater insight into the extent of immunity.
full article