Reconstructing the initial global spread of a human influenza pandemic: A Bayesian spatial-temporal model for the global spread of H1N1pdm

Abstract

Here, we present an analysis of the H1N1pdm genetic data sampled over the initial stages in the epidemic. To infer phylodynamic spread in time and space we employ a recently developed Bayesian statistical inference framework (Lemey et al., in press). We model spatial diffusion as a continuous-time Markov chain process along time-measured genealogies. In this analysis, we consider 40 locations for which sequence data were available on 06-Aug-2009. The sampling time interval of the 242 sequences spans from 30-Mar-2009 to 12-Jul-2009. The Bayesian inference typically results in a posterior distribution of phylogenetic trees, each having an estimate of the epidemic locations at the ancestral nodes in the tree. We summarize these trees using the most representative clustering pattern and annotate these clusters with the most probable location states. We can visualize this information as tree that grows over time, seeding locations each time an ancestral node is inferred to exist at a different location. A Bayes factor test provides statistical support for epidemiological linkage throughout the evolutionary history. We demonstrate how our full probabilistic approach efficiently tracks an epidemic based on viral genetic data as it unfolds across the globe.

Figure 1. The maximum clade credibility (MCC) tree of H1N1pdm with CTMC spatial reconstruction. Lineages are coloured according to the highest posterior probability for location (these probabilities are shown when > 0.5). The blue band represents the 95% credible interval for the time of the most recent common ancestor.

Figure 2. Temporal H1N1pdm dynamics represented by MCC projections over time. Branches which start and finish at different locations are shown at their temporal midpoint. To show the sequence of migrations, branches earlier in the epidemic are in blue, later in purple.

Video 1

Temporal H1N1pdm dynamics visualized using Google Earth. Branches are shown traversing arcs between reconstructed locations over the time they span.

Figure 3. Significant global rates of movement identified by BSSVS. The color of the connections represent the relative strength by which the rates among these two locations are supported: white = weak, magenta = strong.

Figure 4. A more detailed view of significant linkage in North America.