Simulating the effect of public health interventions using dated virus sequences and geographical data
Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak
Perhaps because of its deadliness, the 2013-2016 Ebola Virus (EBOV) epidemics in West-Africa has led to unprecedented publication and sharing of full virus genome sequences. This was both rapid (90 full genomes were shared within weeks ) and important (more than 1500 full genomes have been released overall ). Furthermore, the availability of the metadata (especially GPS location) has led to depth analyses of the geographical spread of the epidemics .
In their work, Dellicour et al.  pursue earlier phylogeographical investigations in an original and yet simple approach to address questions of key public health importance. The originality of the approach is dual. First, from a technical standpoint, they capture the spread of infectious diseases in a continuous framework using a novel model that allows for rare long-distance dispersal events. Second, in a more classical discrete meta-population framework, they simulate the effect of public health interventions by pruning the phylogenetic tree and assessing how this affects key parameters. For instance, to simulate the effect of closing borders they remove subsets of the phylogeny that involved dispersal between countries and to simulate the effect of protecting a region by quarantine they remove all the leaves (i.e. the infections sampled) from this region. This phylogeny pruning is both original and simple. It is however limited because it currently assumes that policies are 100% effective and earlier modelling work on human influenza showed that long distance travel bans had to be implemented with >99% efficiency in order to slow epidemic growth from a time scale of days to weeks .
From a biological standpoint, Dellicour et al.  corroborate earlier findings that highly populated locations (>1,000,000 inhabitants) were crucial in explaining the magnitude of the epidemics but also show the importance of the transmission between the three capital cities. They also show that rare long-distance dispersing events of the virus are not key to explaining the magnitude of the epidemics (even though they assume 100% efficiency of suppressing long-distance event). Finally, thanks to their continuous model they estimate the speed of spread of the epidemics and are able to detect the effect of border closing on this speed.
Overall, this study , which involves state-of-the-art Bayesian inference methods of infection phylogenies using MCMC, stands out because of its effort to simulate public health interventions. It stands as an encouragement for the development of intervention models with increased realism and for even faster and larger virus sequence data sharing.
 Gire et al. 2014. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345: 1369–1372. doi: 10.1126/science.1259657.
 Holmes EC, Dudas G, Rambaut A and Andersen KG. 2016. The evolution of Ebola virus: insights from the 2013-2016 epidemic. Nature 538: 193–200. doi: 10.1038/nature19790.
 Dudas et al. 2017. Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature 544: 309–315 (2017). doi: 10.1038/nature22040.
 Dellicour S, Baele G, Dudas G, Faria NR, Pybus OG, Suchard MA, Rambaud A and Lemey P. 2018. Phylodynamic assessment of intervention strategies for the West African Ebola virus outbreak. bioRxiv, 163691, ver. 3 peer-reviewed by Peer Community In Evolutionary Biology. doi: 10.1101/163691.
 Hollingsworth TD, Ferguson NM and Anderson RM. 2006. Will travel restrictions control the international spread of pandemic influenza? Nature Medicine 12, 497–499. doi: 10.1038/nm0506-497.
Samuel Alizon (2018) Simulating the effect of public health interventions using dated virus sequences and geographical data. Peer Community in Evolutionary Biology, 100046. 10.24072/pci.evolbiol.100046
Revision round #22018-02-08
Decision round #2
The reviewers and I are very happy with this revised version.
I will be happy to write a recommendation.
In the meantime, one of the reviewers suggested some minor edits that could be worth adding.
Reviewed by Chris Wymant, 2018-01-18 14:58
Reviewed by Christian Althaus, 2018-01-18 15:01
Revision round #12018-01-18
Decision round #1
This work offer another very nice illustration of the power of recent advances in phylodynamics when applied to a dataset with dense sampling and rich meta-data (here the location of the infections). It focuses on the recent devastating ebola virus (EBOV) outbreak in West Africa and extends an earlier enormous analysis by Dudas et al. of the by adding a continuous phylogeography approach. It also refines the interpretation of the results by pinpointing the importance of the three capital cities in the magnitude of the outbreak.
Reviewer #1 made some very detailed suggestions and raised a general question about the interpretation of the tree prunning. He/she and Reviewer #2 also made suggestions to broaden the perspective of the article, for instance by discussing epidemiological studies that did not involve phylodynamics to estimate the spread of the epidemics.
In addition to the comments made by the reviewers, I have a couple of my own.
1) Would it be possible to provide confidence intervals for Figure 1 (there are some for panels E, F and G but only for the unprunned tree). The reason why I ask this is because it could help assess the magnitude of the effect. It could also explain why the curves in panels A and B increase at first (I was expecting a steady decrease).
2) Figure 1E is really beautiful! I was wondering if there is an explanation to the fact that recent case counts are below the inferred population size.
3) Figure 2 is also very nice but I expected to be able to find similarities because the sampled data should be the same. However, even the recent timepoints (in blue), which should all I guess be sampled, did not seem to be in the same place.
4) About the model choice (HKY+GAMMA and skygrid) the authors refer to Dudas et al. but it seems that the model choice is not really justified over there, e.g. testing for the most appropriate substitution model. If there is actual support, it would be worth mentionning it. Regarding the details about the priors, I guess the xml files will be made available?