Bayesian Inference Reveals Host-Specific Contributions to the Epidemic Expansion of Influenza A H5N1

Abstract

Since its first isolation in 1996 in Guangdong, China, the highly pathogenic avian influenza virus (HPAIV) H5N1 has circulated in avian hosts for almost two decades and spread to more than 60 countries worldwide. The role of different avian hosts and the domestic-wild bird interface has been critical in shaping the complex HPAIV H5N1 disease ecology, but remains difficult to ascertain. To shed light on the large-scale H5N1 transmission patterns and disentangle the contributions of different avian hosts on the tempo and mode of HPAIV H5N1 dispersal, we apply Bayesian evolutionary inference techniques to comprehensive sets of hemagglutinin and neuraminidase gene sequences sampled between 1996 and 2011 throughout Asia and Russia. Our analyses demonstrate that the large-scale H5N1 transmission dynamics are structured according to different avian flyways, and that the incursion of the Central Asian flyway specifically was driven by Anatidae hosts coinciding with rapid rate of spread and an epidemic wavefront acceleration. This also resulted in long-distance dispersal that is likely to be explained by wild bird migration. We identify a significant degree of asymmetry in the large-scale transmission dynamics between Anatidae and Phasianidae, with the latter largely representing poultry as an evolutionary sink. A joint analysis of host dynamics and continuous spatial diffusion demonstrates that the rate of viral dispersal and host diffusivity is significantly higher for Anatidae compared with Phasianidae. These findings complement risk modeling studies and satellite tracking of wild birds in demonstrating a continental-scale structuring into areas of H5N1 persistence that are connected through migratory waterfowl.

Keywords: Bayesian inference; H5N1; disease ecology; phylogeography; viral evolution.

Fig. 1.

BF support for nonzero rates in HPAIV H5N1 HA and NA. Rates are represented for a BF > 100 in either gene (dashed and dotted lines for HA and NA, respectively) or both genes (full lines). The line color (in the online color figures) represents the relative strength by which the rates are supported: green and red reflect relatively weak and strong support, respectively. When the rate is supported by both HA and NA, the color represents the lowest support for the rate. The thickness of the lines representing the rates is proportional to the number of Markov jumps (MJ): thin and thick reflect a relatively small and large number of MJ, respectively. When the rate is supported for both HA and NA, we set the thickness according to the smallest number of MJ. The representation of the East Asian–Australasian flyway and the Central Asian flyway is adapted from data from the East Asian–Australasian Flyway Partnership (www.eaaflyway.net/the-flyway, last accessed September 15, 2015). The well-supported rates for differently downsampled data sets are shown in supplementary figure S3, Supplementary Material online.

Fig. 2.

Spatiotemporal dispersal of HPAIV H5N1 in Eurasia reconstructed using continuous phylogeographic analysis of HA. Dispersal patterns are shown up to four different years: 2001, 2003, 2005, and 2011. The black lines project the part of the MCC tree up to each of those times, whereas the contours represent statistical uncertainty of the estimated locations at the internal nodes (95% credible contours based on kernel density estimates). The dispersal patterns for the differently downsampled data sets are shown in supplementary figure S4, Supplementary Material online.

Fig. 3.

Host-specific wavefront distance estimates for HA and NA (A). These estimates summarize for each host (Anatidae—Ana, Phasianidae—Pha, and Neoaves—Neo), the fraction of estimated amount of great circle distance from the phylogeographic origin to the wavefront that can be associated with that host according to the host ancestral reconstruction. Host-specific wavefront distance estimates for HAD and NAD are shown in supplementary figure S9, Supplementary Material online. Host-specific densities (B) and diffusion rates (C) summarized for the year 2004 from a joint spatial and host diffusion analysis for HA. The Ana and Pha samples in this analysis are separately represented in the rate (C) and density (B) plot for clarity. In the density plot (B), Ana and Pha densities are represented by a transparent blue and red color (in the online color figures), respectively. High and low dispersal rates are represented by a red-yellow color gradient in the rate plot (in the online color figures) (C).

Fig. 4.

Posterior dispersal rate (top) and diffusion coefficient (bottom) distributions for each host (from left to right: yellow—Neoaves, red—Phasianidae, greengeneral, and blue—Anatidae, in the online color figures) obtained by the joint host analysis of HA (left) and NA (right). Posterior dispersal rate and diffusion coefficient distributions for differently downsampled data sets are shown in supplementary figure S10, Supplementary Material online.