Evolutionary repercussions of avian culling on host resistance and influenza virulence

Abstract

Background: Keeping pandemic influenza at bay is a global health priority. Of particular concern is the continued spread of the influenza subtype H5N1 in avian populations and the increasing frequency of transmission to humans. To decrease this threat, mass culling is the principal strategy for eradicating influenza in avian populations. Although culling has a crucial short-term epidemiological benefit, evolutionary repercussions on reservoir hosts and on the viral population have not been considered.

Methods and findings: To explore the epidemiological and evolutionary repercussions of mass avian culling, we combine population genetics and epidemiological influenza dynamics in a mathematical model parameterized by clinical, epidemiological, and poultry data. We model the virulence level of influenza and the selection on a dominant allele that confers resistance against influenza [1, 2] in a poultry population. Our findings indicate that culling impedes the evolution of avian host resistance against influenza. On the pathogen side of the coevolutionary race between pathogen and host, culling selects for heightened virulence and transmissibility of influenza.

Conclusions: Mass culling achieves a short-term benefit at the expense of long-term detriments: a more genetically susceptible host population, ultimately greater mortality, and elevated influenza virulence.

Figure 1. The effect of culling on disease incidence and on the evolution of genetic resistance for continuous culling policies (a–d) and for a policy that discontinues culling after 2 years (e).

Increases in the culling rate decrease the transient and influenza incidence () and the eventual level of genetic resistance of the population (). Moderate culling (b,c) may shorten the time for the evolution of genetic resistance compared to no culling (a), but fast culling rates (d) will lengthen the evolution time. Very fast culling rates (e) completely suppress an epidemic, but disease can return when culling is discontinued after 2 years. The simultaneous rebound in the susceptible population corresponds to the abrupt decline in overall mortality.

Figure 2. Comparison of outcomes after 10 years for a policy of continuous culling (solid) and a policy where culling is discontinued after 2 years (dashed).

(a) The total disease-dependent mortality decreases with the culling rate under continuous culling, suggesting a decrease in the risk of influenza emergence. Very high rates of culling can completely suppress an epidemic, but discontinuation of culling allows the epidemic to resurge. (b) The total mortality due to infection and culling is significantly greater under a continuous policy than under a 2-year policy. Because high rates of continuous culling will ultimately reduce the population size, less mortality will be attributable to culling than would otherwise be expected. (c) The proportion of the population resistant to infection after 10 years decreases with the culling rate under a continuous policy, but the discontinuation of culling allows resistance to eventually reach the same levels obtained in the absence of culling. (d) The time needed for resistance to reach threshold levels (lower as culling increases) is minimized for culling rates that are approximately equal to the background poultry mortality . For culling rates above , . Note that the resistance threshold is not reached within 10 years for culling rates between and .

Figure 3. Increase in ultimate allele frequency (top line) and disease incidence (bottom line) with declining degree of resistance conferred by the resistance allele.

Degree of resistance is defined as the reduction in the probability of infection compared with a genetically susceptible individual.

Figure 4. Effect of repeated influenza introductions from a wildfowl reservoir.

The effect of repeated emergence of H5N1 on the selection for greater host resistance is negligible until annual rates of emergence reach 10⁵ introductions. The impact of repeated emergence of H5N1 on the rate of influenza evolution towards higher virulence is also negligible for 10⁵ introductions annually. Note that the scale for virulence on the y-axis comprises a very small range.

Figure 5. Decline in resistance evolved as the spatial division increases (filled dot: all patches are connected; empty dot: only neighboring patches are connected).

Spatial structuring slows the rate of resistance evolution and also reduces the equilibrium level of resistance. Comparing spatial structures of different connectivity shows that the greater the connectivity, the greater the equilibrium level of host resistance. When the density of hosts is decreased, epidemic size is reduced, thus the selection for host resistance is lowered.

Figure 6. Decrease in the resistance allele evolved as the rate of selective culling increases.

Selective culling hinders the evolution of host resistance to a much lesser degree than mass culling.

Figure 7

(a) The increase in optimal virulence with culling rate. Virulence is the rate of infection-mediated host mortality. Optimal virulence is a function of culling rate that maximizes overall transmission, i.e. . (b) Optimal virulence coincides with the point where the virulence elasticity of the transmission rate is equal to the virulence elasticity of the rate of infectiousness loss. Increases in the culling rate do not affect the elasticity of transmission but always diminish the elasticity of infectiousness loss, so the optimal virulence increases as the culling rate increases. The virulence elasticity of infectiousness loss is plotted for culling rates , , and .