Extracting transmission networks from phylogeographic data for epidemic and endemic diseases: Ebola virus in Sierra Leone, 2009 H1N1 pandemic influenza and polio in Nigeria

Background: Phylogeography improves our understanding of spatial epidemiology. However, application to practical problems requires choices among computational tools to balance statistical rigor, computational complexity, sensitivity to sampling strategy and interpretability. Methods: We introduce a fast, heuristic algorithm to reconstruct partially-observed transmission networks (POTN) that combines features of phylogenetic and transmission tree approaches. We compare the transmission network generated by POTN with existing algorithms (BEAST and SeqTrack), and discuss the benefits and challenges of phylogeographic analysis on examples of epidemic and endemic diseases: Ebola virus, H1N1 pandemic influenza and polio. Results: For the 2014 Sierra Leone Ebola virus outbreak and the 2009 H1N1 outbreak, all three methods provide similarly plausible transmission histories but differ in detail. For polio in northern Nigeria, we discuss performance trade-offs between the POTN and discrete phylogeography in BEAST and conclude that spatial history reconstruction is limited by under-sampling. Conclusions: POTN is complementary to available tools on densely-sampled data, fails gracefully on under-sampled data and is scalable to accommodate larger datasets. We provide further evidence for the utility of phylogeography for understanding transmission networks of rapidly evolving epidemics. We propose simple heuristic criteria to identify how sampling rates and disease dynamics interact to determine fundamental limitations of phylogeographic inference.