The impact of seasonal and year-round transmission regimes on the evolution of influenza A virus.

Punctuated antigenic change is believed to be a key element in the evolution of influenza A; clusters of antigenically similar strains predominate worldwide for several years until an antigenically distant mutant emerges and instigates a selective sweep. It is thought that a region of East-Southeast Asia with year-round transmission acts as a source of antigenic diversity for influenza A and seasonal epidemics in temperate regions make little contribution to antigenic evolution. We use a mathematical model to examine how different transmission regimes affect the evolutionary dynamics of influenza over the lifespan of an antigenic cluster. Our model indicates that, in non-seasonal regions, mutants that cause significant outbreaks appear before the peak of the wild-type epidemic. A relatively large proportion of these mutants spread globally. In seasonal regions, mutants that cause significant local outbreaks appear each year before the seasonal peak of the wild-type epidemic, but only a small proportion spread globally. The potential for global spread is strongly influenced by the intensity of non-seasonal circulation and coupling between non-seasonal and seasonal regions. Results are similar if mutations are neutral, or confer a weak to moderate antigenic advantage. However, there is a threshold antigenic advantage, depending on the non-seasonal transmission intensity, beyond which mutants can escape herd immunity in the non-seasonal region and there is a global explosion in diversity. We conclude that non-seasonal transmission regions are fundamental to the generation and maintenance of influenza diversity owing to their epidemiology. More extensive sampling of viral diversity in such regions could facilitate earlier identification of antigenically novel strains and extend the critical window for vaccine development.