Contribution of volcanism to the initiation of plague pandemics

The Yersinia pestis bacterium is responsible for the three major plague pandemics of the Common Era, cumulatively responsible for hundreds of millions of deaths and huge societal impacts. Factors influencing the initiation of plague pandemics are still controversial amongst scientists and historians. However recent advances in DNA sequencing and recovery, and ecological and epidemiological modelling, have provided new information regarding the evolution of Y. pestis and the potential influence of climate upon pandemic episodes respectively. Rapid bursts in genetic fixation rates and evolutionary divergences were identified preceding the initiation of the Black Death and Third Pandemic, and climatic factors are now accepted as a key influence upon plague prevalence over an annual to centennial timescale. By reassessing climatic perturbations prior to major pandemics and utilising recent satellite data this thesis suggests a mechanistic pathway linking explosive high sulphur and halogen eruptions within periods of sustained elevated global volcanic forcing, to evolutionary and epidemiological progression of Y. pestis. The periods of global volcanic forcing coincident with pandemic episodes are shown to do the following: (1) increase levels of a known mutagenic element in an area proposed as a source of diversity within the Y. pestis genome through a novel and previously unexplored mechanism and, (2) contribute to regional climatic shifts fully coincident with the timing and distribution of plague immediately preceding pandemic initiation. The volcanic influence suggested not only represents an alternate hypothesis for the genetic expansion and subsequent pandemic impact of plague but also illustrates a previously unexplored risk following large explosive volcanic eruptions

Testing the climatic controls on plague (Yersinia pestis) using palaeobiogeographical modelling and experimental microbiology

Yersinia pestis is the bacterial agent of plague, a disease which has caused three trans-continental pandemics through the Common Era. Y. pestis is currently present in reservoir populations in Asia, Africa, North and South America and has recently been identified as a re-emergent disease primarily due to increasing recorded cases across Africa. Plague is a zoonotic disease, the bacterial agent of which (Y. pestis) is transmitted and maintained primarily through rodent reservoir species and the ectoparasites which feed on them. The Y. pestis zoonotic disease system is therefore highly complex as the dynamics of the bacterium, vector and reservoir species can all impact transmission and dissemination. In this thesis I focus on the niche of Y. pestis at two opposing spatial scales, macroecological and microbiological, and address three gaps in the literature across these scales. Firstly the degree to which reservoir (mammalian host) species locations dictate the distribution of Y. pestis compared to the environmental niche of Y. pestis per se is debated and the transferability of such niches between regions is rarely tested. I assess the niche differences between the Y. pestis at a continental scale across native and invaded ranges, finding that biotic factors, in this case reservoir species distribution, drive such differences. Secondly Y. pestis has commonly been demonstrated to be a highly climatically dynamic disease and subsequently correlations are regularly observed between climatic variables and plague infection among human populations. The mediating factor between these elements of the plague system is often assumed to be a response of reservoir species to climate however the exact mechanisms driving this correlation are poorly resolved. I therefore assess the role that reservoir species play in mediating changes in human plague cases driven by climate perturbations, as has regularly been hypothesised. I find that the response of reservoir species to climatic conditions is highly variable and that even within a similar climatic regime the response of reservoir species to climatic variation should not be assumed to be homogeneous. At the opposing end of the spatial scale much of the literature assumes that unlike it’s most recent ancestors Y. pestis is incapable of persisting independently of host and vector species within the environment. Selected recent works have challenged this assumption by suggesting that Y. pestis may be capable of surviving in soils. However, little work has experimentally tested the survival of Y. pestis in “real world” unsterilised soils or attempted to determine the impact of variables within the soil such as moisture and temperature on Y. pestis survival. Through experimental microbiology, I test the niche of Y. pestis within soil environments independent of reservoir and vector species. Survival of Y. pestis within soils is an often suggested mechanism to explain prolonged periods of quiescence but has yet to be fully integrated into models of the complex plague transmission and maintenance system. My work suggests that soil moisture is a key variable in enabling the persistence of Y. pestis in soil environments. Integrating findings from such disparate scales into a cohesive model of a complex zoonotic disease system is a significant challenge which my work only begins to address. This work is however necessary to avoid the erroneous transfer of assumptions between scales and contexts, which is particularly relevant for plague given the global breadth of distribution in varying environments. My work will hopefully aid in contributing to a more holistic multiscale view of the Y. pestis disease system

Testing the climatic controls on plague (Yersinia pestis) using palaeobiogeographical modelling and experimental microbiology

Yersinia pestis is the bacterial agent of plague, a disease which has caused three trans-continental pandemics through the Common Era. Y. pestis is currently present in reservoir populations in Asia, Africa, North and South America and has recently been identified as a re-emergent disease primarily due to increasing recorded cases across Africa. Plague is a zoonotic disease, the bacterial agent of which (Y. pestis) is transmitted and maintained primarily through rodent reservoir species and the ectoparasites which feed on them. The Y. pestis zoonotic disease system is therefore highly complex as the dynamics of the bacterium, vector and reservoir species can all impact transmission and dissemination. In this thesis I focus on the niche of Y. pestis at two opposing spatial scales, macroecological and microbiological, and address three gaps in the literature across these scales. Firstly the degree to which reservoir (mammalian host) species locations dictate the distribution of Y. pestis compared to the environmental niche of Y. pestis per se is debated and the transferability of such niches between regions is rarely tested. I assess the niche differences between the Y. pestis at a continental scale across native and invaded ranges, finding that biotic factors, in this case reservoir species distribution, drive such differences. Secondly Y. pestis has commonly been demonstrated to be a highly climatically dynamic disease and subsequently correlations are regularly observed between climatic variables and plague infection among human populations. The mediating factor between these elements of the plague system is often assumed to be a response of reservoir species to climate however the exact mechanisms driving this correlation are poorly resolved. I therefore assess the role that reservoir species play in mediating changes in human plague cases driven by climate perturbations, as has regularly been hypothesised. I find that the response of reservoir species to climatic conditions is highly variable and that even within a similar climatic regime the response of reservoir species to climatic variation should not be assumed to be homogeneous. At the opposing end of the spatial scale much of the literature assumes that unlike it’s most recent ancestors Y. pestis is incapable of persisting independently of host and vector species within the environment. Selected recent works have challenged this assumption by suggesting that Y. pestis may be capable of surviving in soils. However, little work has experimentally tested the survival of Y. pestis in “real world” unsterilised soils or attempted to determine the impact of variables within the soil such as moisture and temperature on Y. pestis survival. Through experimental microbiology, I test the niche of Y. pestis within soil environments independent of reservoir and vector species. Survival of Y. pestis within soils is an often suggested mechanism to explain prolonged periods of quiescence but has yet to be fully integrated into models of the complex plague transmission and maintenance system. My work suggests that soil moisture is a key variable in enabling the persistence of Y. pestis in soil environments. Integrating findings from such disparate scales into a cohesive model of a complex zoonotic disease system is a significant challenge which my work only begins to address. This work is however necessary to avoid the erroneous transfer of assumptions between scales and contexts, which is particularly relevant for plague given the global breadth of distribution in varying environments. My work will hopefully aid in contributing to a more holistic multiscale view of the Y. pestis disease system

The role of reservoir species in mediating plague's dynamic response to climate

The distribution and transmission of Yersinia pestis, the bacterial agent of plague, responds dynamically to climate, both within wildlife reservoirs and human populations. The exact mechanisms mediating plague's response to climate are still poorly understood, particularly across large environmentally heterogeneous regions encompassing several reservoir species. A heterogeneous response to precipitation was observed in plague intensity across northern and southern China during the Third Pandemic. This has been attributed to the response of reservoir species in each region. We use environmental niche modelling and hindcasting methods to test the response of a broad range of reservoir species to precipitation. We find little support for the hypothesis that the response of reservoir species to precipitation mediated the impact of precipitation on plague intensity. We instead observed that precipitation variables were of limited importance in defining species niches and rarely showed the expected response to precipitation across northern and southern China. These findings do not suggest that precipitation–reservoir species dynamics never influence plague intensity but that instead, the response of reservoir species to precipitation across a single biome cannot be assumed and that limited numbers of reservoir species may have a disproportional impact upon plague intensity

Multiomic features associated with mucosal healing and inflammation in paediatric Crohn's disease

Background The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD). Aim To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD. Methods Twenty‐five participants aged 3‐18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin 100 μg/g, “mucosal inflammation,” n = 11). 16S gene‐based metataxonomics, 1H‐NMR spectroscopy‐based metabolic profiling and protease activity assays were performed on stool samples. Results Relative abundance of Dialister species was six times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine‐learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35‐times greater in the low calprotectin group (95% CI 1.03‐1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54‐times greater in the high calprotectin group (95% CI 1.05‐2.03, P = 0.028). Conclusions This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with “mucosal healing.” It supports further investigation of these as potential novel therapeutic targets in CD

Thermal sensitivity of feeding and burrowing activity of an invasive crayfish in UK waters

Climate change and invasive species are among the biggest threats to global biodiversity and ecosystem function. Although the individual impacts of climate change and invasive species are commonly assessed, we know far less about how a changing climate may impact invading species. Increases in water temperature due to climate change are likely to alter the thermal regime of UK rivers, and this in turn may influence the performance of invasive species such as signal crayfish (Pacifastacus leniusculus), which are known to have deleterious impacts on native ecosystems. We evaluate the relationship between water temperature and two key performance traits in signal crayfish—feeding and burrowing rate—using thermal experiments on wild‐caught individuals in a laboratory environment. Although water temperature was found to have no significant influence on burrowing rate, it did have a strong effect on feeding rate. Using the thermal performance curve for feeding rate, we evaluate how the thermal suitability of three UK rivers for signal crayfish may change as a result of future warming. We find that warming rivers may increase the amount of time that signal crayfish can achieve high feeding rate levels. These results suggest that elevated river water temperatures as a result of climate change may promote higher signal crayfish performance in the future, further exacerbating the ecological impact of this invasive species

Biotic factors limit the invasion of the plague pathogen ( <i>Yersinia pestis</i> ) in novel geographical settings

Aim: The distribution of Yersinia pestis, the pathogen that causes plague in humans, is reliant upon transmission between host species; however, the degree to which host species distributions dictate the distribution of Y. pestis, compared with limitations imposed by the environmental niche of Y. pestis per se, is debated. We test whether the present-day environmental niche of Y. pestis differs between its native range and an invaded range and whether biotic factors (host distributions) can explain observed discrepancies. Location: North America and Central Asia. Major taxa studied: Yersinia pestis. Methods: We use environmental niche models to determine whether the current climatic niche of Y. pestis differs between its native range in Asia and its invaded range in North America. We then test whether the inclusion of information on the distribution of host species improves the ability of models to capture the North American niche. We use geographical null models to guard against spurious correlations arising from spatially autocorrelated occurrence points. Results: The current climatic niche of Y. pestis differs between its native and invaded regions. The Asian niche overpredicted the distribution of Y. pestis across North America. Including biotic factors along with the native climatic niche increased niche overlap between the native and invaded models, and models containing only biotic factors performed better than the native climatic niche alone. Geographical null models confirmed that the increased niche overlap through inclusion of biotic factors did not, with a couple of exceptions, arise solely from spatially autocorrelated occurrences. Main conclusions: The current climatic niche in Central Asia differs from the current climatic niche in North America. Inclusion of biotic factors improved the fit of models to the Y. pestis distribution data in its invaded region better than climate variables alone. This highlights the importance of host species when investigating zoonotic disease introductions and suggests that climatic variables alone are insufficient to predict disease distribution in novel environments

No evidence for persistent natural plague reservoirs in historical and modern Europe

Caused by Yersinia pestis, plague ravaged the world through three known pandemics: the First or the Justinianic (6th–8th century); the Second (beginning with the Black Death during c.1338–1353 and lasting until the 19th century); and the Third (which became global in 1894). It is debatable whether Y. pestis persisted in European wildlife reservoirs or was repeatedly introduced from outside Europe (as covered by European Union and the British Isles). Here, we analyze environmental data (soil characteristics and climate) from active Chinese plague reservoirs to assess whether such environmental conditions in Europe had ever supported “natural plague reservoirs”. We have used new statistical methods which are validated through predicting the presence of modern plague reservoirs in the western United States. We find no support for persistent natural plague reservoirs in either historical or modern Europe. Two factors make Europe unfavorable for long-term plague reservoirs: 1) Soil texture and biochemistry and 2) low rodent diversity. By comparing rodent communities in Europe with those in China and the United States, we conclude that a lack of suitable host species might be the main reason for the absence of plague reservoirs in Europe today. These findings support the hypothesis that long-term plague reservoirs did not exist in Europe and therefore question the importance of wildlife rodent species as the primary plague hosts in Europe

Reply to Alfani: reconstructing past plague ecology to understand human history

No abstract available

Fauxcurrence: simulating multi-species occurrences for null models in species distribution modelling and biogeography

The work was funded by Newton Fund (UK)/NERC (UK)/RISTEKDIKTI (Indonesia) grants awarded to JT, BJ, ACA, ASTP, CG-R, GB and LTL (grant no.: NE/S006923/1, NE/S006893/1, 2488/IT3.L1/PN/2020 and 3982/IT3.L1/PN/2020). GB and CG-R are funded by Royal Society Univ. Research Fellowships (UF160614 and UF150571 respectively).Peer reviewedPublisher PD