#Climatic and #evolutionary #drivers of phase shifts in the #plague #epidemics of #colonial #India (Proc Natl Acad Sci USA, abstract)

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

Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India

Joseph A. Lewnard a and Jeffrey P. Townsend b,c,d,1

Author Affiliations: a Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520; b Department of Biostatistics, Yale School of Public Health, New Haven, CT 06510; c Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511; d Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520

Edited by Alan Hastings, University of California, Davis, CA, and approved September 23, 2016 (received for review April 29, 2016)



Whereas pathogens are a well-known selective pressure on host immunity, few empirical examples illustrate the coupled dynamics of transmission and evolution. After the arrival of plague in colonial India, a plague-resistant rat phenotype was reported to have become prevalent in the subcontinent’s hardest hit cities. Capitalizing on archival data from these investigations, we identify the evolution of resistance in rats as a driver of observed shifts of seasonal outbreaks in concert with the flea lifecycle and its climatic determinants. Disentangling climatic and evolutionary forcing, our findings—based on century-old observations and experiments by the Indian Plague Commission—substantiate the rapid emergence of host heterogeneity and show how evolutionary responses can buffer host populations against environmentally forced disease dynamics.



Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission exerts intense selective pressure driving the local persistence of disease resistance among its wildlife hosts in endemic areas. Investigations undertaken in colonial India after the introduction of plague in 1896 suggest that, only a decade after plague arrived, a heritable, plague-resistant phenotype had become prevalent among commensal rats of cities undergoing severe plague epidemics. To understand the possible evolutionary basis of these observations, we developed a mathematical model coupling environmentally forced plague dynamics with evolutionary selection of rats, capitalizing on extensive archival data from Indian Plague Commission investigations. Incorporating increased plague resistance among rats as a consequence of intense natural selection permits the model to reproduce observed changes in seasonal epidemic patterns in several cities and capture experimentally observed associations between climate and flea population dynamics in India. Our model results substantiate Victorian era claims of host evolution based on experimental observations of plague resistance and reveal the buffering effect of such evolution against environmental drivers of transmission. Our analysis shows that historical datasets can yield powerful insights into the transmission dynamics of reemerging disease agents with which we have limited contemporary experience to guide quantitative modeling and inference.


1 To whom correspondence should be addressed. Email: Jeffrey.Townsend@Yale.edu.

Author contributions: J.A.L. and J.P.T. designed research; J.A.L. performed research; J.A.L. and J.P.T. contributed new reagents/analytic tools; J.A.L. analyzed data; and J.A.L. and J.P.T. wrote the paper.

The authors declare no conflict of interest.

This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14–15, 2016, at the National Academies of Sciences in Washington, DC. The complete program and video recordings of most presentations are available on the NAS website at http://www.nasonline.org/Coupled_Human_and_Environmental_Systems.

This article is a PNAS Direct Submission.

This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1604985113/-/DCSupplemental.

Keywords: Plague; India.



#Zoonoses As #Ecological #Entities: A Case #Review of #Plague (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]


Zoonoses As Ecological Entities: A Case Review of Plague

Caio Graco Zeppelini , Alzira Maria Paiva de Almeida, Pedro Cordeiro-Estrela

Published: October 6, 2016 / http://dx.doi.org/10.1371/journal.pntd.0004949



As a zoonosis, Plague is also an ecological entity, a complex system of ecological interactions between the pathogen, the hosts, and the spatiotemporal variations of its ecosystems. Five reservoir system models have been proposed: (i) assemblages of small mammals with different levels of susceptibility and roles in the maintenance and amplification of the cycle; (ii) species-specific chronic infection models; (ii) flea vectors as the true reservoirs; (iii) Telluric Plague, and (iv) a metapopulation arrangement for species with a discrete spatial organization, following a source-sink dynamic of extinction and recolonization with naïve potential hosts. The diversity of the community that harbors the reservoir system affects the transmission cycle by predation, competition, and dilution effect. Plague has notable environmental constraints, depending on altitude (500+ meters), warm and dry climates, and conditions for high productivity events for expansion of the transmission cycle. Human impacts are altering Plague dynamics by altering landscape and the faunal composition of the foci and adjacent areas, usually increasing the presence and number of human cases and outbreaks. Climatic change is also affecting the range of its occurrence. In the current transitional state of zoonosis as a whole, Plague is at risk of becoming a public health problem in poor countries where ecosystem erosion, anthropic invasion of new areas, and climate change increase the contact of the population with reservoir systems, giving new urgency for ecologic research that further details its maintenance in the wild, the spillover events, and how it links to human cases.


Citation: Zeppelini CG, de Almeida AMP, Cordeiro-Estrela P (2016) Zoonoses As Ecological Entities: A Case Review of Plague. PLoS Negl Trop Dis 10(10): e0004949. doi:10.1371/journal.pntd.0004949

Editor: Juan Olano, UTMB, UNITED STATES

Published: October 6, 2016

Copyright: © 2016 Zeppelini et al. 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.

Funding: The authors received no specific funding for this work.

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

Keywords: Research; Abstracts; Zoonoses; Plague.


#Xenopsylla brasiliensis #Fleas in #Plague Focus #Areas, #Madagascar (@CDC_EIDjournal, extract)

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

Volume 22, Number 12—December 2016 / Letter

Xenopsylla brasiliensis Fleas in Plague Focus Areas, Madagascar


To the Editor:

Plague is a life-threatening infectious disease caused by the gram-negative bacterium Yersinia pestis (1). Y. pestis primarily infects rodents but can also cause outbreaks of plague in humans. The infection is usually transmitted within murine populations and then to humans by bites from infected fleas. The oriental rat flea, Xenopsylla cheopis, is considered the most efficient plague vector (1). Plague remains a major public health threat, causing annual epidemics, especially in Madagascar.



Adélaïde Miarinjara, Christophe Rogier, Mireille Harimalala, Tojo R. Ramihangihajason, and Sébastien Boyer

Author affiliations: Université d’Antananarivo, Antananarivo, Madagascar (A. Miarinjara); Institut Pasteur, Antananarivo (A. Miarinjara, C. Rogier, M. Harimalala, T.R. Ramihangihajason, S. Boyer)

Suggested citation for this article: Miarinjara A, Rogier C, Harimalala M, Ramihangihajason TR, Boyer S. Xenopsylla brasiliensis fleas in plague focus areas, Madagascar. Emerg Infect Dis. 2016 Dec [date cited]. http://dx.doi.org/10.3201/eid2212.160318

DOI: 10.3201/eid2212.160318

Keywords: Research; Plague; Madagascar; Xenopsylla choepis.


Adjunctive #Corticosteroid #Treatment Against #Yersinia pestis Improves Bacterial Clearance, #Immunopathology and Survival in the Mouse Model of Bubonic #Plague (J Infect Dis., abstract)

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

Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology and Survival in the Mouse Model of Bubonic Plague

Y. Levy, Y. Vagima, A. Tidhar, A. Zauberman, M. Aftalion, D. Gur, I. Fogel1, T. Chitlaru, Y Flashner and E. Mamroud

Author Affiliations: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel  – 1Surgeon General Headquarters, IDF Medical Corps, Tel Hashomer, Israel

Correspondence: Emanuelle Mamroud, Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, Israel, Tel: +972-8-9381523, Fax: +972-8-9381544, E-mail: emmym@iibr.gov.il




Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of anti-plague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague.


Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-plague antibodies alone or in combination with the corticosteroid methylprednisolone.


The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase-9 in the tissues and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs.


Corticosteroids induce an unexpectedly effective anti-bacterial response apart from their anti-inflammatory properties, thereby improving treatment efficacy.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Research; Abstracts; Yersinia Pestis; Corticosteroids; Bubonic Plague; Plague.


Historical Y. pestis #Genomes Reveal the European #BlackDeath as the #Source of Ancient and Modern #Plague #Pandemics (Cell Host Microbe, abstract)

[Source: Cell Host & Microbe, full page: (LINK). Abstract, edited.]

Short Article

Historical Y. pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics

Maria A. Spyrou, Rezeda I. Tukhbatova, Michal Feldman, Joanna Drath, Sacha Kacki, Julia Beltrán de Heredia, Susanne Arnold, Airat G. Sitdikov, Dominique Castex, Joachim Wahl, Ilgizar R. Gazimzyanov, Danis K. Nurgaliev, Alexander Herbigc, Kirsten I. Bos, Johannes Krause

DOI: http://dx.doi.org/10.1016/j.chom.2016.05.012

Publication History: Published: June 8, 2016Accepted: May 13, 2016Received in revised form: April 23, 2016Received: March 4, 2016



  • Three historical Yersinia pestis genomes from the second plague pandemic in Europe
  • Low genetic diversity of the pathogen during the Black Death
  • Indication for link between the Black Death and 19th century plague pandemic lineages
  • Connection between post-Black Death outbreaks in Europe supports a local plague focus



Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14th century Black Death until the mid-18th century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300–1420 cal AD), Bolgar City, Russia (1362–1400 AD), and Ellwangen, Germany (1485–1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct.

Received: March 4, 2016; Received in revised form: April 23, 2016; Accepted: May 13, 2016; Published: June 8, 2016

© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

Keywords: Research; Abstracts; Yersinia Pestis; Bubonic Plague; Plague; Black Death.


#Epidemiological #analysis of the #Eyam #plague #outbreak of 1665–1666 (Proc R Soc B., abstract)

[Source: Proceedings of the Royal Society B, full page: (LINK). Abtsract, edited.]

Epidemiological analysis of the Eyam plague outbreak of 1665–1666

Lilith K. Whittles, Xavier Didelot

Published 11 May 2016. DOI: 10.1098/rspb.2016.0618



Plague, caused by the bacterium Yersinia pestis, is one of the deadliest infectious diseases in human history, and still causes worrying outbreaks in Africa and South America. Despite the historical and current importance of plague, several questions remain unanswered concerning its transmission routes and infection risk factors. The plague outbreak that started in September 1665 in the Derbyshire village of Eyam claimed 257 lives over 14 months, wiping out entire families. Since previous attempts at modelling the Eyam plague, new data have been unearthed from parish records revealing a much more complete record of the disease. Using a stochastic compartmental model and Bayesian analytical methods, we found that both rodent-to-human and human-to-human transmission played an important role in spreading the infection, and that they accounted, respectively, for a quarter and three-quarters of all infections, with a statistically significant seasonality effect. We also found that the force of infection was stronger for infectious individuals living in the same household compared with the rest of the village. Poverty significantly increased the risk of disease, whereas adulthood decreased the risk. These results on the Eyam outbreak contribute to the current debate on the relative importance of plague transmission routes.

Keywords: Research; Abstracts; Plague; Yersinia Pestis.


Detections of #Yersinia pestis East of the Known Distribution of Active #Plague in the #US (Vector Borne Zoo Dis., abstract)

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

Vector-Borne and Zoonotic Diseases

Detections of Yersinia pestis East of the Known Distribution of Active Plague in the United States  [      ][      ]

To cite this article: Mize Erica L. and Britten Hugh B.. Vector-Borne and Zoonotic Diseases. January 2016, ahead of print. doi:10.1089/vbz.2015.1825.

Online Ahead of Print: January 15, 2016

Author information: Erica L. Mize and Hugh B. Britten, Department of Biology, University of South Dakota, Vermillion, South Dakota.

Address correspondence to: Erica L. Mize, U.S. Fish and Wildlife Service Midwest Fisheries Center, Whitney Genetics Laboratory, 555 Lester Avenue, Onalaska, WI 54650, E-mail: ericamize@gmail.com



We examined fleas collected from black-tailed prairie dog (Cynomys ludovicianus) burrows from 2009 through 2011 in five national park units east of the known distribution of active plague across the northern Great Plains for the presence of Yersinia pestis. Across all national park units, Oropsylla tuberculata and Oropsylla hirsuta were the most common fleas collected from prairie dog burrows, 42.4% and 56.9%, respectively, of the 3964 fleas collected from burrow swabbing. Using a nested PCR assay we detected 200 Y. pestis–positive fleas from 3117 assays. In total, 6.4% of assayed fleas were Y. pestis positive and 13.9% of prairie dog burrows swabbed contained Y. pestis–positive fleas. Evidence of the presence of Y. pestis was observed at all national park units except Devils Tower National Monument in Wyoming. We detected the presence of Y. pestis without large die-offs, i.e., enzootic sylvatic plague, east of the known distribution of active plague and near the eastern edge of the present distribution of black-tailed prairie dogs. This study, in combination with previous work suggests that sylvatic plague likely occurs across the range of black-tailed prairie dogs and should now be treated as endemic across this range.

Keywords: Research; Abstracts; Plague; Yersinia Pestis; Wildlife; USA; Wyoming.