#Ancient #Yersinia pestis #genomes from across Western #Europe reveal early diversification during the First #Pandemic (541–750) (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541–750)

Marcel Keller, Maria A. Spyrou, Christiana L. Scheib, Gunnar U. Neumann, Andreas Kröpelin, Brigitte Haas-Gebhard, Bernd Päffgen, Jochen Haberstroh, Albert Ribera i Lacomba, Claude Raynaud, Craig Cessford, Raphaël Durand, Peter Stadler, Kathrin Nägele, Jessica S. Bates, Bernd Trautmann, Sarah A. Inskip, Joris Peters, John E. Robb, Toomas Kivisild, Dominique Castex, Michael McCormick, Kirsten I. Bos, Michaela Harbeck, Alexander Herbig, and Johannes Krause

PNAS first published June 4, 2019 / DOI: https://doi.org/10.1073/pnas.1820447116

Edited by Nils Chr. Stenseth, University of Oslo, Oslo, Norway, and approved May 9, 2019 (received for review November 30, 2018)



The first historically reported pandemic attributed to Yersinia pestis started with the Justinianic Plague (541–544) and continued for around 200 y as the so-called First Pandemic. To date, only one Y. pestis strain from this pandemic has been reconstructed using ancient DNA. In this study, we present eight genomes from Britain, France, Germany, and Spain, demonstrating the geographic range of plague during the First Pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemics (14th to 18th century) that includes the same two virulence factors, thus providing an example of potential convergent evolution of Y. pestis during large-scale epidemics.



The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium’s spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

Justinianic Plague – ancient DNA – bacterial evolution – Anglo-Saxons – Merovingians

Keywords: Yersinia pestis; Plague.


#Historical and #genomic data reveal the influencing factors on global #transmission #velocity of #plague during the Third #Pandemic (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Historical and genomic data reveal the influencing factors on global transmission velocity of plague during the Third Pandemic

Lei Xu, Leif C. Stige, Herwig Leirs, Simon Neerinckx, Kenneth L. Gage, Ruifu Yang, Qiyong Liu, Barbara Bramanti, Katharine R. Dean, Hui Tang, Zhe Sun, Nils Chr. Stenseth, and Zhibin Zhang

PNAS first published May 28, 2019 / DOI: https://doi.org/10.1073/pnas.1901366116

Contributed by Nils Chr. Stenseth, April 9, 2019 (sent for review January 28, 2019; reviewed by Javier Pizarro-Cerda and Qiwei Yao)



Plague is a devastating infectious disease that has caused three pandemics during the last millennia. Today, plague still causes sporadic cases every year and even some outbreaks. In this paper, we analyze how factors associated with climate change and globalization affect the spread of plague worldwide. Such information is important with respect to global disease prevention and control. For this purpose, we first constructed a global plague database of the Third Pandemic, and then analyzed the association of spatiotemporal environmental factors with spreading velocity. Our results provide insight into the global transmission and suggest strategies for preventing plague transmission under accelerated global change.



Quantitative knowledge about which natural and anthropogenic factors influence the global spread of plague remains sparse. We estimated the worldwide spreading velocity of plague during the Third Pandemic, using more than 200 years of extensive human plague case records and genomic data, and analyzed the association of spatiotemporal environmental factors with spreading velocity. Here, we show that two lineages, 2.MED and 1.ORI3, spread significantly faster than others, possibly reflecting differences among strains in transmission mechanisms and virulence. Plague spread fastest in regions with low population density and high proportion of pasture- or forestland, findings that should be taken into account for effective plague monitoring and control. Temperature exhibited a nonlinear, U-shaped association with spread speed, with a minimum around 20 °C, while precipitation showed a positive association. Our results suggest that global warming may accelerate plague spread in warm, tropical regions and that the projected increased precipitation in the Northern Hemisphere may increase plague spread in relevant regions.

Yersinia pestis – Third Pandemic – climate change – global transmission velocity – historical and genomic data

Keywords: Yersinia pestis; Plague.


Shift from primary #pneumonic to secondary #septicemic #plague by decreasing the volume of intranasal challenge with #Yersinia pestis in the murine model (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]


Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestis in the murine model

Rachel M. Olson , Deborah M. Anderson

Published: May 23, 2019 / DOI: https://doi.org/10.1371/journal.pone.0217440



Yersinia pestis is the causative agent of pneumonic plague, a disease involving uncontrolled bacterial growth and host immunopathology. Secondary septicemic plague commonly occurs as a consequence of the host inflammatory response that causes vasodilation and vascular leakage, which facilitates systemic spread of the bacteria and the colonization of secondary tissues. The mortality rates of pneumonic and septicemic plague are high even when antibiotics are administered. In this work, we show that primary pneumonic or secondary septicemic plague can be preferentially modeled in mice by varying the volume used for intranasal delivery of Y. pestis. Low volume intranasal challenge (10μL) of wild type Y. pestis resulted in a high frequency of lethal secondary septicemic plague, with a low degree of primary lung infection and rapid development of sepsis. In contrast, high volume intranasal challenge (30μL) yielded uniform early lung infection and primary disease and a significant increase in lethality. In a commonly used BSL2 model, high volume challenge with Y. pestis lacking the pigmentation locus (pgm-) gave 105-fold greater deposition compared to low volume challenge, yet moribund mice did not develop severe lung disease and there was no detectable difference in lethality. These data indicate the primary cause of death of mice in the BSL2 model is sepsis regardless of intranasal dosing method. Overall, these findings allow for the preferential modeling of pneumonic or septicemic plague by intranasal dosing of mice with Y. pestis.


Citation: Olson RM, Anderson DM (2019) Shift from primary pneumonic to secondary septicemic plague by decreasing the volume of intranasal challenge with Yersinia pestisin the murine model. PLoS ONE 14(5): e0217440. https://doi.org/10.1371/journal.pone.0217440

Editor: Matthew B. Lawrenz, University of Louisville School of Medicine, UNITED STATES

Received: February 24, 2019; Accepted: May 10, 2019; Published: May 23, 2019

Copyright: © 2019 Olson, Anderson. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: Financial support for this work came from the National Institutes of Health/ National Institute of Allergy and Infectious Disease, public health service award #R01A129996 (DA). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yersinia pestis; Pneumonic plague; Septicemic plague; Sepsis; Animal models.


#Plague in #SanFrancisco: #rats, #racism and #reform (Nature, summary)

[Source: Nature, full page: (LINK). Summary, edited.]

Plague in San Francisco: rats, racism and reform

Tilli Tansey


An urban outbreak of a deadly infectious disease with no known cause is a disaster planner’s worst nightmare. In his rousing book Black Death at the Golden Gate, journalist David Randall describes just that: the bubonic-plague epidemic that struck San Francisco, California, in 1900. The race to identify, isolate and halt the disease is set against a rich background of official complacency, financial malfeasance, political intrigues and scientific disputes.



Nature 568, 454-455 (2019) / doi: 10.1038/d41586-019-01239-x

Keywords: Plague; USA; California; History.


#Plague-Positive #Mouse #Fleas on Mice Before Plague Induced Die-Offs in Black-Tailed and White-Tailed Prairie Dogs (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Plague-Positive Mouse Fleas on Mice Before Plague Induced Die-Offs in Black-Tailed and White-Tailed Prairie Dogs

Gebbiena M. Bron, Carly M. Malavé, Jesse T. Boulerice, Jorge E. Osorio, and Tonie E. Rocke

Published Online: 17 Apr 2019 / DOI: https://doi.org/10.1089/vbz.2018.2322



Plague is a lethal zoonotic disease associated with rodents worldwide. In the western United States, plague outbreaks can decimate prairie dog (Cynomys spp.) colonies. However, it is unclear where the causative agent, Yersinia pestis, of this flea-borne disease is maintained between outbreaks, and what triggers plague-induced prairie dog die-offs. Less susceptible rodent hosts, such as mice, could serve to maintain the bacterium, transport infectious fleas across a colony, or introduce the pathogen to other colonies, possibly facilitating an outbreak. Here, we assess the potential role of two short-lived rodent species, North American deer mice (Peromyscus maniculatus) and Northern grasshopper mice (Onychomys leucogaster) in plague dynamics on prairie dog colonies. We live-trapped short-lived rodents and collected their fleas on black-tailed (Cynomys ludovicianus, Montana and South Dakota), white-tailed (Cynomys leucurus, Utah and Wyoming), and Utah prairie dog colonies (Cynomys parvidens, Utah) annually, from 2013 to 2016. Plague outbreaks occurred on colonies of all three species. In all study areas, deer mouse abundance was high the year before plague-induced prairie dog die-offs, but mouse abundance per colony was not predictive of plague die-offs in prairie dogs. We did not detect Y. pestis DNA in mouse fleas during prairie dog die-offs, but in three cases we found it beforehand. On one white-tailed prairie dog colony, we detected Y. pestis positive fleas on one grasshopper mouse and several prairie dogs live-trapped 10 days later, months before visible declines and plague-confirmed mortality of prairie dogs. On one black-tailed prairie dog colony, we detected Y. pestispositive fleas on two deer mice 3 months before evidence of plague was detected in prairie dogs or their fleas and also well before a plague-induced die-off. These observations of plague positive fleas on mice could represent early spillover events of Y. pestis from prairie dogs or an unknown reservoir, or possible movement of infectious fleas by mice.

Keywords: Yersinia pestis; Plague; Fleas; USA.


#Epidemiological characteristics of an #urban #plague #epidemic in #Madagascar, August–November, 2017: an outbreak #report (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Epidemiological characteristics of an urban plague epidemic in Madagascar, August–November, 2017: an outbreak report

Rindra Randremanana, PhD, Voahangy Andrianaivoarimanana, PhD, Birgit Nikolay, PhD, Beza Ramasindrazana, PhD, Juliette Paireau, PhD, Quirine Astrid ten Bosch, PhD, Jean Marius Rakotondramanga, MSc, Soloandry Rahajandraibe, MSc, Soanandrasana Rahelinirina, PhD, Fanjasoa Rakotomanana, PhD, Feno M Rakotoarimanana, MD, Léa Bricette Randriamampionona, MD, Vaoary Razafimbia, MD, Prof Mamy Jean De Dieu Randria, MD, Mihaja Raberahona, MD, Guillain Mikaty, PhD, Anne-Sophie Le Guern, PharmD, Lamina Arthur Rakotonjanabelo, MSc, Prof Charlotte Faty Ndiaye, MD, Voahangy Rasolofo, PhD, Eric Bertherat, MD, Maherisoa Ratsitorahina, MD, Simon Cauchemez, PhD, Laurence Baril, MD, André Spiegel, MD, Minoarisoa Rajerison, PhD

Open Access / Published: March 28, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30730-8




Madagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200–700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings.


Clinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations.


2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (<1%) septicaemic case, and 140 (6%) cases with unspecified clinical form. 386 (21%) of 1878 notified pneumonic plague cases were probable and 32 (2%) were confirmed. 73 (18%) of 395 notified bubonic plague cases were probable and 66 (17%) were confirmed. The case fatality ratio was higher among confirmed cases (eight [25%] of 32 cases) than probable (27 [8%] of 360 cases) or suspected pneumonic plague cases (74 [5%] of 1358 cases) and a similar trend was seen for bubonic plague cases (16 [24%] of 66 confirmed cases, four [6%] of 68 probable cases, and six [2%] of 243 suspected cases). 351 (84%) of 418 confirmed or probable pneumonic plague cases were concentrated in Antananarivo, the capital city, and Toamasina, the main seaport. All 50 isolated Yersinia pestis strains were susceptible to the tested antibiotics.


This predominantly urban plague epidemic was characterised by a large number of notifications in two major urban areas and an unusually high proportion of pneumonic forms, with only 23% having one or more positive laboratory tests. Lessons about clinical and biological diagnosis, case definition, surveillance, and the logistical management of the response identified in this epidemic are crucial to improve the response to future plague outbreaks.


US Agency for International Development, WHO, Institut Pasteur, US Department of Health and Human Services, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, AXA Research Fund, and the INCEPTION programme.

Keywords: Yersinia pestis; Plague; Bubonic plague; Pneumonic plague; Madagascar.


#Pneumonic #Plague in a #Dog and Widespread Potential #Human #Exposure in a #Veterinary Hospital, #USA (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 4—April 2019 / Dispatch

Pneumonic Plague in a Dog and Widespread Potential Human Exposure in a Veterinary Hospital, United States

Paula A. Schaffer1, Stephanie A. Brault1, Connor Hershkowitz1, Lauren Harris, Kristy Dowers, Jennifer House, Tawfik A. Aboellail, Paul S. Morley, and Joshua B. Daniels

Author affiliations: Colorado State University, Fort Collins, Colorado, USA (P.A. Schaffer, S.A. Brault, C. Hershkowitz, L. Harris, K. Dowers, T.A. Aboellail, P.S. Morley, J.B. Daniels); Colorado Department of Public Health and Environment, Denver, Colorado, USA (J. House)



In December 2017, a dog that had pneumonic plague was brought to a veterinary teaching hospital in northern Colorado, USA. Several factors, including signalment, season, imaging, and laboratory findings, contributed to delayed diagnosis and resulted in potential exposure of >116 persons and 46 concurrently hospitalized animals to Yersinia pestis.

Keywords: Yersinia pestis; Plague; Pneumonic plague; Dogs; USA; Colorado.