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Plague synchronously swept across separated regions in Europe throughout history. However, the spatio-temporal synchrony of plague and its driving mechanism have not been thoroughly investigated. In this study, we transformed the historical European plague database spanned 1347-1800 CE into country-level time-series that differentiated large-scale plague outbreak from counted data. We found that there are 74 years in which two or more countries in our study region (UK, France, Germany, Spain, and Italy) experienced large-scale plague outbreak in the same year. Our Multivariate Ripley's K-function results showed that the onset year and the cessation year of large-scale plague outbreak are synchronized at the 0-23-year and 0-20-year windows, respectively. The temporal association between such synchrony and climatic forcing was further investigated using the Superposed Epoch Analysis, and drought was found to be responsible for the synchrony. Integrating our results with a literature survey, we suggested that prior to the peak of plague, the occurrence of drought and the subsequent reintroduced rainfall dampened both the rodent community and human society and boosted the number of fleas that carried plague. Such a synthesis facilitated the outbreak of plague. At the same time, high temperature associated with such drought also confined the geographic diffusion of the plague. Hence, although continental mega-drought could initiate the synchrony of plague outbreak, the synchrony actually consisted of a number of localized plague outbreak events scattering across different regions in Europe. According to the projected rising trend of drought in terms of its magnitude, duration, and geographic extent, the risk of synchrony of rodent-borne diseases in Europe will be significantly elevated, especially in France, Italy, and Spain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although the linkage between climate change and plague transmission has been proposed in previous studies, the dominant approach has been to address the linkage with traditional statistical methods, while the possible non-linearity, non-stationarity and low frequency domain of the linkage has not been fully considered. We seek to address the above issue by investigating plague transmission in pre-industrial Europe (AD1347-1760) at both continental and country levels., Methods: We apply Granger Causality Analysis to identify the casual relationship between climatic variables and plague outbreaks. We then apply Wavelet Analysis to explore the non-linear and non-stationary association between climate change and plague outbreaks., Results: Our results show that 5-year lagged temperature and aridity index are the significant determinants of plague outbreaks in pre-industrial Europe. At the multi-decadal time scale, there are more frequent plague outbreaks in a cold and arid climate. The synergy of temperature and aridity index, rather than their individual effect, is more imperative in driving plague outbreaks, which is valid at both the continental and country levels., Conclusions: Plague outbreaks come after cold and dry spells. The multi-decadal climate variability is imperative in driving the cycles of plague outbreaks in pre-industrial Europe. The lagged and multi-decadal effect of climate change on plague outbreaks may be attributable to the complexity of ecological, social, or climate systems, through which climate exerts its influence on plague dynamics. These findings may contribute to improve our understanding of the epidemiology of plague and other rodent-borne or flea-borne infectious diseases in human history.

Numerous historical works have mentioned that trade routes were to blame for the spread of plague in European history, yet this relationship has never been tested by quantitative evidence. Here, we resolve the hypothetical role of trade routes through statistical analysis on the geo-referenced major trade routes in the early modern period and the 6,656 geo-referenced plague outbreak records in AD1347-1760. Ordinary Least Square (OLS) estimation results show that major trade routes played a dominant role in spreading plague in pre-industrial Europe. Furthermore, the negative correlation between plague outbreaks and their distance from major trade ports indicates the absence of a permanent plague focus in the inland areas of Europe. Major trade routes decided the major plague outbreak hotspots, while navigable rivers determined the geographic pattern of sporadic plague cases. A case study in Germany indicates that plague penetrated further into Europe through the local trade route network. Based on our findings, we propose the mechanism of plague transmission in historical Europe, which is imperative in demonstrating how pandemics were spread in recent human history.