Final Report Summary - PLAGUEECO2GENO (Reconstructing the imprint of ecology on the genetic phylogeography of the Plague in Central Asia and China.) The main goal of PlagueEco2Geno was to “improve our limited understanding of the underlying cause of plague outbreaks in human populations”. Significant progress towards this goal has been achieved. The approach taken has deviated from proposed methods, in part to take advantage of the new developments in the microbiological knowledge on plague since the date that the proposal was drafted (June 2011).The original approach was to compare the phylogeography of plague to a simulated phylogeography, initially for a desert system, and later on to be extended to multiple ecosystems in Asia, with the intent to study the conditions under which when large-scale plague outbreaks would occur in wildlife rodents that might affect humans. However, during the starting phase of the project we realized that we could use medieval datasets of plague outbreaks, such as the historical record compiled by Jean-Noël Biraben in 1975 of the second plague pandemic in Europe, to approach our problem from the human perspective. It allowed us to work from a position where we knew beforehand that the conditions in the rodent populations caused a plague outbreak in humans. After a considerable period of exploring the complex dataset of 7710 documented plague outbreaks in Europe, and linking it to socioeconomic, paleoclimatic, epidemiological, historical and geographical factors, we successfully identified (first purely on a statistical basis, and secondly under a more mechanical description) an unexpected climate-based driver of plague outbreaks in medieval and early modern Europe. Namely, that the climate-sensitive Asian plague reservoirs, from which the Black Death is supposed to have originated, continued to contribute significantly to the plague outbreaks in Medieval Europe. This finding is in contrast to the prevailing view that the Black Death in 1354 was a singular event, in which the plague was introduced and established in Europe. We find no support in our analysis for the idea of a European wildlife rodent reservoir of plague existed, although we do not exclude that both wildlife and urban rodents in Europe might have formed transient reservoirs of the disease. These results have now been disseminated through international workshops and conferences, and are in the process of publication. The socio-economical impact of our results is an increased understanding of the role of regional reservoirs of disease during prolonged pandemic events, and is in that regard important for the animal-borne infectious disease sectors of public health institutes worldwide. In addition to this main line of research, the researcher funded by the project is collaborating with two Chinese research groups, sharing knowledge, expertise and data on human plague epidemiology, plague genetic diversity, and plague rodent reservoir ecology (notably on ground squirrels and gerbils, two plague reservoir species in northern and northwestern China). As China is host to numerous plague systems, involving many different host species, the potential for groundbreaking science on the role of climate in the ecology and epidemiology of plague is high.