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Sample records for bubonic plague model

  1. Kinetics of disease progression and host response in a rat model of bubonic plague.

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    Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B; Hinnebusch, B Joseph

    2005-05-01

    Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.

  2. Recent results on the spatiotemporal modelling and comparative analysis of Black Death and bubonic plague epidemics

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    Christakos, G.; Olea, R.A.; Yu, H.-L.

    2007-01-01

    Background: This work demonstrates the importance of spatiotemporal stochastic modelling in constructing maps of major epidemics from fragmentary information, assessing population impacts, searching for possible etiologies, and performing comparative analysis of epidemics. Methods: Based on the theory previously published by the authors and incorporating new knowledge bases, informative maps of the composite space-time distributions were generated for important characteristics of two major epidemics: Black Death (14th century Western Europe) and bubonic plague (19th-20th century Indian subcontinent). Results: The comparative spatiotemporal analysis of the epidemics led to a number of interesting findings: (1) the two epidemics exhibited certain differences in their spatiotemporal characteristics (correlation structures, trends, occurrence patterns and propagation speeds) that need to be explained by means of an interdisciplinary effort; (2) geographical epidemic indicators confirmed in a rigorous quantitative manner the partial findings of isolated reports and time series that Black Death mortality was two orders of magnitude higher than that of bubonic plague; (3) modern bubonic plague is a rural disease hitting harder the small villages in the countryside whereas Black Death was a devastating epidemic that indiscriminately attacked large urban centres and the countryside, and while the epidemic in India lasted uninterruptedly for five decades, in Western Europe it lasted three and a half years; (4) the epidemics had reverse areal extension features in response to annual seasonal variations. Temperature increase at the end of winter led to an expansion of infected geographical area for Black Death and a reduction for bubonic plague, reaching a climax at the end of spring when the infected area in Western Europe was always larger than in India. Conversely, without exception, the infected area during winter was larger for the Indian bubonic plague; (5) during the

  3. Recent results on the spatiotemporal modelling and comparative analysis of Black Death and bubonic plague epidemics.

    Science.gov (United States)

    Christakos, G; Olea, R A; Yu, H-L

    2007-09-01

    This work demonstrates the importance of spatiotemporal stochastic modelling in constructing maps of major epidemics from fragmentary information, assessing population impacts, searching for possible etiologies, and performing comparative analysis of epidemics. Based on the theory previously published by the authors and incorporating new knowledge bases, informative maps of the composite space-time distributions were generated for important characteristics of two major epidemics: Black Death (14th century Western Europe) and bubonic plague (19th-20th century Indian subcontinent). The comparative spatiotemporal analysis of the epidemics led to a number of interesting findings: (1) the two epidemics exhibited certain differences in their spatiotemporal characteristics (correlation structures, trends, occurrence patterns and propagation speeds) that need to be explained by means of an interdisciplinary effort; (2) geographical epidemic indicators confirmed in a rigorous quantitative manner the partial findings of isolated reports and time series that Black Death mortality was two orders of magnitude higher than that of bubonic plague; (3) modern bubonic plague is a rural disease hitting harder the small villages in the countryside whereas Black Death was a devastating epidemic that indiscriminately attacked large urban centres and the countryside, and while the epidemic in India lasted uninterruptedly for five decades, in Western Europe it lasted three and a half years; (4) the epidemics had reverse areal extension features in response to annual seasonal variations. Temperature increase at the end of winter led to an expansion of infected geographical area for Black Death and a reduction for bubonic plague, reaching a climax at the end of spring when the infected area in Western Europe was always larger than in India. Conversely, without exception, the infected area during winter was larger for the Indian bubonic plague; (5) during the Indian epidemic, the disease

  4. Spatiotemporal modelling and mapping of the bubonic plague epidemic in India

    Directory of Open Access Journals (Sweden)

    Christakos George

    2006-03-01

    Full Text Available Abstract Background This work studies the spatiotemporal evolution of bubonic plague in India during 1896–1906 using stochastic concepts and geographical information science techniques. In the past, most investigations focused on selected cities to conduct different kinds of studies, such as the ecology of rats. No detailed maps existed incorporating the space-time dependence structure and uncertainty sources of the epidemic system and providing a composite space-time picture of the disease propagation characteristics. Results Informative spatiotemporal maps were generated that represented mortality rates and geographical spread of the disease, and epidemic indicator plots were derived that offered meaningful characterizations of the spatiotemporal disease distribution. The bubonic plague in India exhibited strong seasonal and geographical features. During its entire duration, the plague continued to invade new geographical areas, while it followed a re-emergence pattern at many localities; its rate changed significantly during each year and the mortality distribution exhibited space-time heterogeneous patterns; prevalence usually occurred in the autumn and spring, whereas the plague stopped moving towards new locations during the summers. Conclusion Modern stochastic modelling and geographical information science provide powerful means to study the spatiotemporal distribution of the bubonic plague epidemic under conditions of uncertainty and multi-sourced databases; to account for various forms of interdisciplinary knowledge; and to generate informative space-time maps of mortality rates and propagation patterns. To the best of our knowledge, this kind of plague maps and plots become available for the first time, thus providing novel perspectives concerning the distribution and space-time propagation of the deadly epidemic. Furthermore, systematic maps and indicator plots make possible the comparison of the spatial-temporal propagation

  5. Spatiotemporal modelling and mapping of the bubonic plague epidemic in India.

    Science.gov (United States)

    Yu, Hwa-Lung; Christakos, George

    2006-03-17

    This work studies the spatiotemporal evolution of bubonic plague in India during 1896-1906 using stochastic concepts and geographical information science techniques. In the past, most investigations focused on selected cities to conduct different kinds of studies, such as the ecology of rats. No detailed maps existed incorporating the space-time dependence structure and uncertainty sources of the epidemic system and providing a composite space-time picture of the disease propagation characteristics. Informative spatiotemporal maps were generated that represented mortality rates and geographical spread of the disease, and epidemic indicator plots were derived that offered meaningful characterizations of the spatiotemporal disease distribution. The bubonic plague in India exhibited strong seasonal and geographical features. During its entire duration, the plague continued to invade new geographical areas, while it followed a re-emergence pattern at many localities; its rate changed significantly during each year and the mortality distribution exhibited space-time heterogeneous patterns; prevalence usually occurred in the autumn and spring, whereas the plague stopped moving towards new locations during the summers. Modern stochastic modelling and geographical information science provide powerful means to study the spatiotemporal distribution of the bubonic plague epidemic under conditions of uncertainty and multi-sourced databases; to account for various forms of interdisciplinary knowledge; and to generate informative space-time maps of mortality rates and propagation patterns. To the best of our knowledge, this kind of plague maps and plots become available for the first time, thus providing novel perspectives concerning the distribution and space-time propagation of the deadly epidemic. Furthermore, systematic maps and indicator plots make possible the comparison of the spatial-temporal propagation patterns of different diseases.

  6. Vaccination against bubonic and pneumonic plague.

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    Titball, R W; Williamson, E D

    2001-07-20

    Yersinia pestis is the etiological agent of bubonic and pneumonic plague, diseases which have caused over 200 milllion human deaths in the past. Plague still occurs throughout the world today, though for reasons that are not fully understood pandemics of disease do not develop from these outbreaks. Antibiotic treatment of bubonic plague is usually effective, but pneumonic plague is difficult to treat and even with antibiotic therapy death often results. A killed whole cell plague vaccine has been used in the past, but recent studies in animals have shown that this vaccine offers poor protection against pneumonic disease. A live attenuated vaccine is also available. Whilst this vaccine is effective, it retains some virulence and in most countries it is not considered to be suitable for use in humans. We review here work to develop improved sub-unit and live attenuated vaccines against plague. A sub-unit vaccine based on the F1- and V-antigens is highly effective against both bubonic and pneumonic plague, when tested in animal models of disease. This vaccine has been used to explore the utility of different intranasal and oral delivery systems, based on the microencapsulation or Salmonella delivery of sub-units.

  7. Model-based analysis of an outbreak of bubonic plague in Cairo in 1801.

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    Didelot, Xavier; Whittles, Lilith K; Hall, Ian

    2017-06-01

    Bubonic plague has caused three deadly pandemics in human history: from the mid-sixth to mid-eighth century, from the mid-fourteenth to the mid-eighteenth century and from the end of the nineteenth until the mid-twentieth century. Between the second and the third pandemics, plague was causing sporadic outbreaks in only a few countries in the Middle East, including Egypt. Little is known about this historical phase of plague, even though it represents the temporal, geographical and phylogenetic transition between the second and third pandemics. Here we analysed in detail an outbreak of plague that took place in Cairo in 1801, and for which epidemiological data are uniquely available thanks to the presence of medical officers accompanying the Napoleonic expedition into Egypt at that time. We propose a new stochastic model describing how bubonic plague outbreaks unfold in both rat and human populations, and perform Bayesian inference under this model using a particle Markov chain Monte Carlo. Rat carcasses were estimated to be infectious for approximately 4 days after death, which is in good agreement with local observations on the survival of infectious rat fleas. The estimated transmission rate between rats implies a basic reproduction number R0 of approximately 3, causing the collapse of the rat population in approximately 100 days. Simultaneously, the force of infection exerted by each infected rat carcass onto the human population increases progressively by more than an order of magnitude. We also considered human-to-human transmission via pneumonic plague or human specific vectors, but found this route to account for only a small fraction of cases and to be significantly below the threshold required to sustain an outbreak. © 2017 The Author(s).

  8. Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis.

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    Gonzalez, Rodrigo J; Weening, Eric H; Lane, M Chelsea; Miller, Virginia L

    2015-07-01

    Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including Yersinia pestis pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c. We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i.d. but not s.c. inoculation. Moreover, a deletion mutant of rovA, previously shown to be moderately attenuated in the s.c. model, was severely attenuated in the i.d. Lastly, based on previous observations where a population bottleneck from the skin to lymph nodes was observed after i.d., but not after s.c., inoculations, we used the latter model as a strategy to identify an additional bottleneck in bacterial dissemination from lymph nodes to the bloodstream. Our data indicate that the more biologically relevant i.d. model of bubonic plague differs significantly from the s.c. model in multiple aspects of infection. These findings reveal adaptations of Y. pestis to the dermis and how these adaptations can define the progression of disease. They also emphasize the importance of using a relevant route of infection when addressing host-pathogen interactions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Analysis of the sensitivity properties of a model of vector-borne bubonic plague.

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    Buzby, Megan; Neckels, David; Antolin, Michael F; Estep, Donald

    2008-09-06

    Model sensitivity is a key to evaluation of mathematical models in ecology and evolution, especially in complex models with numerous parameters. In this paper, we use some recently developed methods for sensitivity analysis to study the parameter sensitivity of a model of vector-borne bubonic plague in a rodent population proposed by Keeling & Gilligan. The new sensitivity tools are based on a variational analysis involving the adjoint equation. The new approach provides a relatively inexpensive way to obtain derivative information about model output with respect to parameters. We use this approach to determine the sensitivity of a quantity of interest (the force of infection from rats and their fleas to humans) to various model parameters, determine a region over which linearization at a specific parameter reference point is valid, develop a global picture of the output surface, and search for maxima and minima in a given region in the parameter space.

  10. Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague.

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    Jarrett, Clayton O; Sebbane, Florent; Adamovicz, Jeffrey J; Andrews, Gerard P; Hinnebusch, B Joseph

    2004-04-01

    A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 x 10(8) Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.

  11. Human anti-plague monoclonal antibodies protect mice from Yersinia pestis in a bubonic plague model.

    Directory of Open Access Journals (Sweden)

    Xiaodong Xiao

    2010-10-01

    Full Text Available Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252 and two anti-V-specific human mAb (m253, m254 by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.

  12. A Deadly Path: Bacterial Spread During Bubonic Plague.

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    Gonzalez, Rodrigo J; Miller, Virginia L

    2016-04-01

    Yersinia pestis causes bubonic plague, a fulminant disease where host immune responses are abrogated. Recently developed in vivo models of plague have resulted in new ideas regarding bacterial spread in the body. Deciphering bacterial spread is key to understanding Y. pestis and the immune responses it encounters during infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Bubonic and pneumonic plague - Uganda, 2006.

    Science.gov (United States)

    2009-07-24

    Plague is a life-threatening fleaborne disease caused by the bacterium Yersinia pestis. The most common clinical form is bubonic plague, which is characterized by high fever and regional lymphadenitis. Without treatment, infection can spread from lymph nodes to the lungs, resulting in pneumonic plague and the potential for person-to-person transmission through respiratory droplets. In November 2006, the Uganda Ministry of Health received reports of an increase in bubonic plague cases and a possible outbreak of pneumonic plague among residents in the Arua and Nebbi districts. In response, the Uganda Ministry of Health and CDC conducted a joint investigation in the two districts during November 28-December 30, 2006. Overall, 127 clinical plague cases were identified, along with evidence of a focal pneumonic outbreak in Nebbi District. Median age of the patients was 14 years (range: 2 weeks-65 years); 65 (51%) were female. Twenty-eight (22%) of the 127 patients died. Among the 102 patients with documented symptoms, 90 (88%) had bubonic plague, and 12 (12%) had pneumonic plague. The results of this investigation underscore the need to 1) continue efforts to educate residents of rural Uganda regarding the source, signs, and symptoms of plague and the life-saving importance of seeking treatment; 2) strengthen plague surveillance and diagnostic capabilities; and 3) improve emergency response and vector-control capacity, especially in remote regions of the country.

  14. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

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    Zauberman, Ayelet; Tidhar, Avital; Levy, Yinon; Bar-Haim, Erez; Halperin, Gideon; Flashner, Yehuda; Cohen, Sara; Shafferman, Avigdor; Mamroud, Emanuelle

    2009-06-16

    An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7)-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50) of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the

  15. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Ayelet Zauberman

    Full Text Available An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed

  16. Yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague.

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    Shannon, Jeffrey G; Hasenkrug, Aaron M; Dorward, David W; Nair, Vinod; Carmody, Aaron B; Hinnebusch, B Joseph

    2013-08-27

    The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host's innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d. Y. pestis infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. Yersinia pestis remains a public health concern today because of sporadic plague outbreaks that occur throughout the world and the potential for its illegitimate use as a bioterrorism weapon. Since bubonic plague pathogenesis is initiated by the introduction of Y. pestis into the skin, we sought to characterize the response of the host's innate immune cells to bacteria early after

  17. The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

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    Flashner, Yehuda; Fisher, Morly; Tidhar, Avital; Mechaly, Adva; Gur, David; Halperin, Gideon; Zahavy, Eran; Mamroud, Emanuelle; Cohen, Sara

    2010-07-01

    Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease. In a mouse model of pneumonic plague, LcrV can be determined in the bronchoalveolar lavage fluid somewhat later than F1, but before dissemination of Y. pestis to the blood. Thus, determination of soluble LcrV is suggested as a potential useful tool for monitoring disease progression in both bubonic and pneumonic plague. Moreover, it may be of particular advantage in cases of infections with F1 nonproducing strains.

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

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    Levy, Yinon; Vagima, Yaron; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Gur, David; Fogel, Itay; Chitlaru, Theodor; Flashner, Yehuda; Mamroud, Emanuelle

    2016-09-15

    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 antiplague 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-Y. pestis 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 antibacterial response apart from their antiinflammatory 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.

  19. Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus

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    Gascuel, Fanny; Choisy, Marc; Duplantier, Jean-Marc; Débarre, Florence; Brouat, Carine

    2013-01-01

    Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar. PMID:23675291

  20. Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus.

    Science.gov (United States)

    Gascuel, Fanny; Choisy, Marc; Duplantier, Jean-Marc; Débarre, Florence; Brouat, Carine

    2013-01-01

    Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

  1. Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus.

    Directory of Open Access Journals (Sweden)

    Fanny Gascuel

    Full Text Available Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i endemicity is favoured by intermediate host population sizes, (ii in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

  2. Modelling the black death. A historical case study and implications for the epidemiology of bubonic plague.

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    Monecke, Stefan; Monecke, Hannelore; Monecke, Jochen

    2009-12-01

    We analysed a plague outbreak in the mining town of Freiberg in Saxony which started in May 1613 and ended in February 1614. This epidemic was selected for study because of the high quality of contemporary sources. It was possible to identify 1400 individual victims meaning that more than 10% of the population of the city perished. The outbreak was modelled by 9 differential equations describing flea, rat, and human populations. This resulted in a close fit to the historical records of this outbreak. An interesting implication of the model is that the introduction of even a small number of immune rats into an otherwise unchanged setting results in an abortive outbreak with very few human victims. Hence, the percentage of immune rats directly influences the magnitude of a human epidemic by diverting search activities of the fleas. Thus, we conclude that the spread of Rattus norvegicus, which might acquire partial herd immunity by exposure to soil- or water-borne Yersinia species due to its preference for wet habitats, contributed to the disappearance of Black Death epidemics from Europe in the 18th century. In order to prove whether or not the parameter values obtained by fitting a given outbreak are also applicable to other cases, we modelled the plague outbreak in Bombay 1905/06 using the same parameter values except for the number of humans as well as of immune and susceptible rats.

  3. CpG oligodeoxynucleotides augment the murine immune response to the Yersinia pestis F1-V vaccine in bubonic and pneumonic models of plague.

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    Amemiya, Kei; Meyers, Jennifer L; Rogers, Taralyn E; Fast, Randy L; Bassett, Anthony D; Worsham, Patricia L; Powell, Bradford S; Norris, Sarah L; Krieg, Arthur M; Adamovicz, Jeffrey J

    2009-04-06

    The current U.S. Department of Defense candidate plague vaccine is a fusion between two Yersinia pestis proteins: the F1 capsular protein, and the low calcium response (Lcr) V-protein. We hypothesized that an immunomodulator, such as CpG oligodeoxynucleotide (ODN)s, could augment the immune response to the plague F1-V vaccine in a mouse model for plague. CpG ODNs significantly augmented the antibody response and efficacy of a single dose of the plague vaccine in murine bubonic and pneumonic models of plague. In the latter study, we also found an overall significant augmentation the immune response to the individual subunits of the plague vaccine by CpG ODN 2006. In a long-term, prime-boost study, CpG ODN induced a significant early augmentation of the IgG response to the vaccine. The presence of CpG ODN induced a significant increase in the IgG2a subclass response to the vaccine up to 5 months after the boost. Our studies showed that CpG ODNs significantly augmented the IgG antibody response to the plague vaccine, which increased the probability of survival in murine models of plague (P<0.0001).

  4. Urban epidemic of bubonic plague in Majunga, Madagascar: epidemiological aspects.

    Science.gov (United States)

    Boisier, P; Rasolomaharo, M; Ranaivoson, G; Rasoamanana, B; Rakoto, L; Andrianirina, Z; Andriamahefazafy, B; Chanteau, S

    1997-05-01

    After an absence of 62 years, an epidemic of plague occurred in the harbour city of Majunga (Madagascar) from July 1995 to March 1996, following sporadic cases in March and May 1995. By 15 March 1996, 617 clinically suspected cases of bubonic plague had been notified. Laboratory testing was carried out for 394 individuals: 60 (15.2%) were confirmed to have bubonic plague and 48 (12.2%) were considered as presumptive cases. The incidence was significantly higher in males in all age groups and in both sexes in the 5-19 age group. Twenty-four deaths were related to plague, but early treatment with streptomycin has confirmed its effectiveness insofar as the case-farality ratio was only 8.7% among confirmed and presumptive cases admitted to hospital. The difficulty of clinically diagnosing bubonic plague was affirmed. The disease met favourable conditions through the poverty and low level of hygiene prevalent in most parts of Majunga.

  5. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.

    Science.gov (United States)

    van Lier, Christina J; Sha, Jian; Kirtley, Michelle L; Cao, Anthony; Tiner, Bethany L; Erova, Tatiana E; Cong, Yingzi; Kozlova, Elena V; Popov, Vsevolod L; Baze, Wallace B; Chopra, Ashok K

    2014-06-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4(+) and CD8(+) T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.

  6. Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague

    Science.gov (United States)

    van Lier, Christina J.; Sha, Jian; Kirtley, Michelle L.; Cao, Anthony; Tiner, Bethany L.; Erova, Tatiana E.; Cong, Yingzi; Kozlova, Elena V.; Popov, Vsevolod L.; Baze, Wallace B.

    2014-01-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4+ and CD8+ T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection. PMID:24686064

  7. Paleoclimate and bubonic plague: a forewarning of future risk?

    Science.gov (United States)

    McMichael, Anthony J

    2010-08-27

    Pandemics of bubonic plague have occurred in Eurasia since the sixth century AD. Climatic variations in Central Asia affect the population size and activity of the plague bacterium's reservoir rodent species, influencing the probability of human infection. Using innovative time-series analysis of surrogate climate records spanning 1,500 years, a study in BMC Biology concludes that climatic fluctuations may have influenced these pandemics. This has potential implications for health risks from future climate change.

  8. Neutralization of Yersinia pestis-mediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plague.

    Science.gov (United States)

    Zauberman, Ayelet; Cohen, Sara; Levy, Yinon; Halperin, Gideon; Lazar, Shirley; Velan, Baruch; Shafferman, Avigdor; Flashner, Yehuda; Mamroud, Emanuelle

    2008-03-20

    Plague is a life-threatening disease caused by Yersinia pestis, for which effective-licensed vaccines and reliable predictors of in vivo immunity are lacking. V antigen (LcrV) is a major Y. pestis virulence factor that mediates translocation of the cytotoxic Yersinia protein effectors (Yops). It is a well-established protective antigen and a part of currently tested plague subunit vaccines. We have developed a highly sensitive in vitro macrophage cytotoxicity neutralization assay which is mediated by anti-LcrV antibodies; and studied the potential use of these neutralizing antibodies as an in vitro correlate of plague immunity in mice. The assay is based on a Y. pestis strain with enhanced cytotoxicity to macrophages in which endogenous yopJ was replaced by the more effectively translocated yopP of Y. enterocolitica O:8. Mice passively immunized with rabbit anti-LcrV IgG or actively immunized with recombinant LcrV were protected against lethal doses of a virulent Y. pestis strain, in a mouse model of bubonic plague. This protection significantly correlated with the in vitro neutralizing activity of the antisera but not with their corresponding ELISA titers. In actively immunized mice, a cutoff value for serum neutralizing activity, above which survival was assured with high degree of confidence, could be established for different vaccination regimes. The impact of overall findings on the potential use of serum neutralizing activity as a correlate of protective immunity is discussed.

  9. Prevention of bubonic and pneumonic plague using plant-derived vaccines.

    Science.gov (United States)

    Alvarez, M Lucrecia; Cardineau, Guy A

    2010-01-01

    Yersinia pestis, the causative agent of bubonic and pneumonic plague, is an extremely virulent bacterium but there are currently no approved vaccines for protection against this organism. Plants represent an economical and safer alternative to fermentation-based expression systems for the production of therapeutic proteins. The recombinant plague vaccine candidates produced in plants are based on the two most immunogenic antigens of Y. pestis: the fraction-1 capsular antigen (F1) and the low calcium response virulent antigen (V) either in combination or as a fusion protein (F1-V). These antigens have been expressed in plants using all three known possible strategies: nuclear transformation, chloroplast transformation and plant-virus-based expression vectors. These plant-derived plague vaccine candidates were successfully tested in animal models using parenteral, oral, or prime/boost immunization regimens. This review focuses on the recent research accomplishments towards the development of safe and effective pneumonic and bubonic plague vaccines using plants as bioreactors.

  10. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague

    National Research Council Canada - National Science Library

    Lemaître, Nadine; Ricard, Isabelle; Pradel, Elizabeth; Foligné, Benoît; Courcol, René; Simonet, Michel; Sebbane, Florent

    2012-01-01

    ... (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN...

  11. Paleoclimate and bubonic plague: a forewarning of future risk?

    Directory of Open Access Journals (Sweden)

    McMichael Anthony J

    2010-08-01

    Full Text Available Abstract Pandemics of bubonic plague have occurred in Eurasia since the sixth century ad. Climatic variations in Central Asia affect the population size and activity of the plague bacterium's reservoir rodent species, influencing the probability of human infection. Using innovative time-series analysis of surrogate climate records spanning 1,500 years, a study in BMC Biology concludes that climatic fluctuations may have influenced these pandemics. This has potential implications for health risks from future climate change. See research article http://www.biomedcentral.com/1741-7007/8/112

  12. Solar Variability and the Decline of the Bubonic Plague

    Science.gov (United States)

    2001-10-01

    The bubonic plague was responsible for the deaths of a very large percentage of the population of Europe in ancient times. Leaders of state made promises to “kill off” the plague, were all unsuccessful. It wasn’t the grand promise of a politician, or some new medicinal invention that was responsible for the final decline of the plague. It appears that a chain of events that began 93,000,000 miles away from Earth exerted an impact that lead to the end of the plague’s activity. Some simple changes in solar activity that began in the early 1300’s started the final to break the stranglehold that the plague had on most of Europe. This chain of events will be presented and discussed in this paper.

  13. The Yersinia pestis caf1M1A1 fimbrial capsule operon promotes transmission by flea bite in a mouse model of bubonic plague.

    Science.gov (United States)

    Sebbane, Florent; Jarrett, Clayton; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

    2009-03-01

    Plague is a zoonosis transmitted by fleas and caused by the gram-negative bacterium Yersinia pestis. During infection, the plasmidic caf1M1A1 operon that encodes the Y. pestis F1 protein capsule is highly expressed, and anti-F1 antibodies are protective. Surprisingly, the capsule is not required for virulence after injection of cultured bacteria, even though it is an antiphagocytic factor and capsule-deficient Y. pestis strains are rarely isolated. We found that a caf-negative Y. pestis mutant was not impaired in either flea colonization or virulence in mice after intradermal inoculation of cultured bacteria. In contrast, absence of the caf operon decreased bubonic plague incidence after a flea bite. Successful development of plague in mice infected by flea bite with the caf-negative mutant required a higher number of infective bites per challenge. In addition, the mutant displayed a highly autoaggregative phenotype in infected liver and spleen. The results suggest that acquisition of the caf locus via horizontal transfer by an ancestral Y. pestis strain increased transmissibility and the potential for epidemic spread. In addition, our data support a model in which atypical caf-negative strains could emerge during climatic conditions that favor a high flea burden. Human infection with such strains would not be diagnosed by the standard clinical tests that detect F1 antibody or antigen, suggesting that more comprehensive surveillance for atypical Y. pestis strains in plague foci may be necessary. The results also highlight the importance of studying Y. pestis pathogenesis in the natural context of arthropod-borne transmission.

  14. Transcriptomic and innate immune responses to Yersinia pestis in the lymph node during bubonic plague.

    Science.gov (United States)

    Comer, Jason E; Sturdevant, Daniel E; Carmody, Aaron B; Virtaneva, Kimmo; Gardner, Donald; Long, Dan; Rosenke, Rebecca; Porcella, Stephen F; Hinnebusch, B Joseph

    2010-12-01

    A delayed inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response to Y. pestis and how it is influenced by the Yersinia virulence plasmid (pYV). Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression or cytokine response by host lymph node cells in the developing bubo. Only after systemic spread had led to terminal septicemic plague was a transcriptomic response detected, which included upregulation of several cytokine, chemokine, and other immune response genes. Although an initial intracellular phase of Y. pestis infection has been postulated, a Th1-type cytokine response associated with classical activation of macrophages was not observed during the bubonic stage of disease. However, elevated levels of interleukin-17 (IL-17) were present in infected lymph nodes. In the absence of pYV, sustained recruitment to the lymph node of polymorphonuclear leukocytes (PMN, or neutrophils), the major IL-17 effector cells, correlated with clearance of infection. Thus, the ability to counteract a PMN response in the lymph node appears to be a major in vivo function of the Y. pestis virulence plasmid.

  15. Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague.

    Science.gov (United States)

    Guinet, Françoise; Avé, Patrick; Filali, Sofia; Huon, Christèle; Savin, Cyril; Huerre, Michel; Fiette, Laurence; Carniel, Elisabeth

    2015-10-01

    Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN) draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla is to protect

  16. Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague.

    Directory of Open Access Journals (Sweden)

    Françoise Guinet

    2015-10-01

    Full Text Available Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla

  17. A live attenuated strain of Yersinia pestis ΔyscB provides protection against bubonic and pneumonic plagues in mouse model.

    Science.gov (United States)

    Zhang, Xuecan; Qi, Zhizhen; Du, Zongmin; Bi, Yujing; Zhang, Qingwen; Tan, Yafang; Yang, Huiying; Xin, Youquan; Yang, Ruifu; Wang, Xiaoyi

    2013-05-24

    To develop a safe and effective live plague vaccine, the ΔyscB mutant was constructed based on Yersinia pestis biovar Microtus strain 201 that is avirulent to humans, but virulent to mice. The virulence, immunogenicity and protective efficacy of the ΔyscB mutant were evaluated in this study. The results showed that the ΔyscB mutant was severely attenuated, elicited a higher F1-specific antibody titer and provided protective efficacy against bubonic and pneumonic plague in mouse model. The ΔyscB mutant could induce the secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4 and IL-10). Taken together, the ΔyscB mutant represented a potential vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses and to provide good protection against both subcutaneous and intranasal Y. pestis challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. New insights into how Yersinia pestis adapts to its mammalian host during bubonic plague.

    Directory of Open Access Journals (Sweden)

    Elizabeth Pradel

    2014-03-01

    Full Text Available Bubonic plague (a fatal, flea-transmitted disease remains an international public health concern. Although our understanding of the pathogenesis of bubonic plague has improved significantly over the last few decades, researchers have still not been able to define the complete set of Y. pestis genes needed for disease or to characterize the mechanisms that enable infection. Here, we generated a library of Y. pestis mutants, each lacking one or more of the genes previously identified as being up-regulated in vivo. We then screened the library for attenuated virulence in rodent models of bubonic plague. Importantly, we tested mutants both individually and using a novel, "per-pool" screening method that we have developed. Our data showed that in addition to genes involved in physiological adaptation and resistance to the stress generated by the host, several previously uncharacterized genes are required for virulence. One of these genes (ympt1.66c, which encodes a putative helicase has been acquired by horizontal gene transfer. Deletion of ympt1.66c reduced Y. pestis' ability to spread to the lymph nodes draining the dermal inoculation site--probably because loss of this gene decreased the bacteria's ability to survive inside macrophages. Our results suggest that (i intracellular survival during the early stage of infection is important for plague and (ii horizontal gene transfer was crucial in the acquisition of this ability.

  19. New insights into how Yersinia pestis adapts to its mammalian host during bubonic plague.

    Science.gov (United States)

    Pradel, Elizabeth; Lemaître, Nadine; Merchez, Maud; Ricard, Isabelle; Reboul, Angéline; Dewitte, Amélie; Sebbane, Florent

    2014-03-01

    Bubonic plague (a fatal, flea-transmitted disease) remains an international public health concern. Although our understanding of the pathogenesis of bubonic plague has improved significantly over the last few decades, researchers have still not been able to define the complete set of Y. pestis genes needed for disease or to characterize the mechanisms that enable infection. Here, we generated a library of Y. pestis mutants, each lacking one or more of the genes previously identified as being up-regulated in vivo. We then screened the library for attenuated virulence in rodent models of bubonic plague. Importantly, we tested mutants both individually and using a novel, "per-pool" screening method that we have developed. Our data showed that in addition to genes involved in physiological adaptation and resistance to the stress generated by the host, several previously uncharacterized genes are required for virulence. One of these genes (ympt1.66c, which encodes a putative helicase) has been acquired by horizontal gene transfer. Deletion of ympt1.66c reduced Y. pestis' ability to spread to the lymph nodes draining the dermal inoculation site--probably because loss of this gene decreased the bacteria's ability to survive inside macrophages. Our results suggest that (i) intracellular survival during the early stage of infection is important for plague and (ii) horizontal gene transfer was crucial in the acquisition of this ability.

  20. Yersinia pestis YopJ suppresses tumor necrosis factor alpha induction and contributes to apoptosis of immune cells in the lymph node but is not required for virulence in a rat model of bubonic plague.

    Science.gov (United States)

    Lemaître, Nadine; Sebbane, Florent; Long, Daniel; Hinnebusch, B Joseph

    2006-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system that transfers six Yop effector proteins into host cells. One of these proteins, YopJ, has been shown to disrupt host cell signaling pathways involved in proinflammatory cytokine production and to induce macrophage apoptosis in vitro. YopJ-dependent apoptosis in mesenteric lymph nodes has also been demonstrated in a mouse model of Yersinia pseudotuberculosis infection. These results suggest that YopJ attenuates the host innate and adaptive immune response during infection, but the role of YopJ during bubonic plague has not been completely established. We evaluated the role of Yersinia pestis YopJ in a rat model of bubonic plague following intradermal infection with a fully virulent Y. pestis strain and an isogenic yopJ mutant. Deletion of yopJ resulted in a twofold decrease in the number of apoptotic immune cells in the bubo and a threefold increase in serum tumor necrosis factor alpha levels but did not result in decreased virulence, systemic spread, or colonization levels in the spleen and blood. Our results indicate that YopJ is not essential for bubonic plague pathogenesis, even after peripheral inoculation of low doses of Y. pestis. Instead, the effects of YopJ appear to overlap and augment the immunomodulatory effects of other Y. pestis virulence factors.

  1. Shutt up: bubonic plague and quarantine in early modern England.

    Science.gov (United States)

    Newman, Kira L S

    2012-01-01

    The outbreak of bubonic plague that struck London and Westminster in 1636 provoked the usual frenzied response to epidemics, including popular flight and government-mandated quarantine. The government asserted that plague control measures were acts of public health for the benefit of all. However, contrary to this government narrative of disease prevention there was a popular account that portrayed quarantine and isolation as personal punishment rather than prudent policy. In examining the 1636 outbreak on the parish as well as the individual level, reasons for this inconsistency between official and unofficial perspectives emerge. Quarantine and its effects were not classless, and its implementation was not always strictly in the name of public health. Government application of quarantine was remarkably effective, but it could never be uncontroversial both because of circumstances and because of misuse. The flight of the wealthiest from London and Westminster left only the more socially vulnerable to be quarantined. Though plague policy was financially sensitive to the poorest, it was costly to the middling sort. Another cause of controversy was the government's use of quarantine as a punishment to control individuals found breaking other laws. Though not widely publicized, popular narratives continually included grievances about the cruelty and inequity of quarantine and the militaristic nature of its implementation. Despite these objections, quarantine remained a staple of the government response to plague outbreaks throughout the seventeenth century.

  2. The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague.

    Science.gov (United States)

    Fetherston, Jacqueline D; Kirillina, Olga; Bobrov, Alexander G; Paulley, James T; Perry, Robert D

    2010-05-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an approximately 24-fold-higher 50% lethal dose (LD(50)) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.

  3. Epidemiologic Features of Four Successive Annual Outbreaks of Bubonic Plague in Mahajanga, Madagascar

    OpenAIRE

    Boisier, Pascal; Rahalison, Lila; Rasolomaharo, Monique; Ratsitorahina, Maherisoa; Mahafaly, Mahafaly; Razafimahefa, Maminirana; Duplantier, Jean-Marc; Ratsifasoamanana, Lala; Chanteau, Suzanne

    2002-01-01

    From 1995 to 1998, outbreaks of bubonic plague occurred annually in the coastal city of Mahajanga, Madagascar. A total of 1,702 clinically suspected cases of bubonic plague were reported, including 515 laboratory confirmed by Yersinia pestis isolation (297), enzyme-linked immunosorbent assay, or both. Incidence was higher in males and young persons. Most buboes were inguinal, but children had a higher frequency of cervical or axillary buboes. Among laboratory-confirmed hospitalized patients, ...

  4. Quick control of bubonic plague outbreak in Uttar Kashi, India.

    Science.gov (United States)

    Mittal, Veena; Rana, U V S; Jain, S K; Kumar, Kaushal; Pal, I S; Arya, R C; Ichhpujani, R L; Lal, Shiv; Agarwal, S P

    2004-12-01

    A localized outbreak of bubonic plague occurred in village Dangud (population 332), district Uttar Kashi, Uttaranchal, India in the second week of October 2004. 8 cases were considered outbreak associated based on their clinical and epidemiological characteristics; 3 (27.3%) of them died within 48 hours of developing illness. All the 3 fatal cases and five surviving cases had enlargement of inguinal lymph nodes. None of them had pneumonia. The age of the cases ranged from 23-70 years and both sexes were affected. No such illness was reported from adjoining villages. The outbreak was fully contained within two weeks of its onset by supervised comprehensive chemoprophylaxis using tetracycline. A total of approximately 1250 persons were given chemoprophylaxis in three villages. There was no clear history of rat fall in the village. No flea was found on rodents or animals. 16 animal serum samples were found to be negative for antibodies against F-1 antigen of Y. pestis. However, Y. pestis was isolated from two rodents (Rattus rattus and Mus musculus) trapped in the village. One case and three animal sera showed borderline sero-positivity against rickettsial infection. The diagnosis of plague was confirmed by detection of four fold rise of antibody titre against F-1 antigen of Yersinia pestis in paired sera of three cases (one of the WHO approved criteria of diagnosis of confirmed plague). This outbreak and the occurrence of earlier outbreaks of plague in Surat (Gujarat) and Beed (Maharashtra) in 1994 and in district Shimla (Himachal Pradesh) in 2002 confirm that plague infection continue to exist in sylvatic foci in many parts of India which is transmitted to humans occasionally. Thus, there is a strong need for the States to monitor the plague activity in known sylvatic foci regularly and have a system of surveillance to facilitate prompt diagnosis and treatment of cases to control the disease. This investigation highlights that with high index of suspicion the

  5. Role of the Yersinia pestis Ail protein in preventing a protective polymorphonuclear leukocyte response during bubonic plague.

    Science.gov (United States)

    Hinnebusch, B Joseph; Jarrett, Clayton O; Callison, Julie A; Gardner, Donald; Buchanan, Susan K; Plano, Gregory V

    2011-12-01

    The ability of Yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The Y. pestis ail mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in vitro. Intradermal infection with the ail mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive adaptive immune response was generated after high-dose challenge, as evidenced by high serum antibody levels against Y. pestis F1 antigen. The Y. pestis Ail protein is an important bubonic plague virulence factor that inhibits the innate immune response, in particular the recruitment of a protective PMN response to the infected lymph node.

  6. A Yersinia pestis YscN ATPase mutant functions as a live attenuated vaccine against bubonic plague in mice.

    Science.gov (United States)

    Bozue, Joel; Cote, Christopher K; Webster, Wendy; Bassett, Anthony; Tobery, Steven; Little, Stephen; Swietnicki, Wieslaw

    2012-07-01

    Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. The bacterium uses the pLcr plasmid-encoded type III secretion system to deliver virulence factors into host cells. Delivery requires ATP hydrolysis by the YscN ATPase encoded by the yscN gene also on pLcr. A yscN mutant was constructed in the fully virulent CO92 strain containing a nonpolar, in-frame internal deletion within the gene. We demonstrate that CO92 with a yscN mutation was not able to secrete the LcrV protein (V-Antigen) and attenuated in a subcutaneous model of plague demonstrating that the YscN ATPase was essential for virulence. However, if the yscN mutant was complemented with a functional yscN gene in trans, virulence was restored. To evaluate the mutant as a live vaccine, Swiss-Webster mice were vaccinated twice with the ΔyscN mutant at varying doses and were protected against bubonic plague in a dose-dependent manner. Antibodies to F1 capsule but not to LcrV were detected in sera from the vaccinated mice. These preliminary results suggest a proof-of-concept for an attenuated, genetically engineered, live vaccine effective against bubonic plague. Published 2012. This article is a US Government work and is in the public domain in the USA.

  7. Epidemiologic features of four successive annual outbreaks of bubonic plague in Mahajanga, Madagascar.

    Science.gov (United States)

    Boisier, Pascal; Rahalison, Lila; Rasolomaharo, Monique; Ratsitorahina, Maherisoa; Mahafaly, Mahafaly; Razafimahefa, Maminirana; Duplantier, Jean-Marc; Ratsifasoamanana, Lala; Chanteau, Suzanne

    2002-03-01

    From 1995 to 1998, outbreaks of bubonic plague occurred annually in the coastal city of Mahajanga, Madagascar. A total of 1,702 clinically suspected cases of bubonic plague were reported, including 515 laboratory confirmed by Yersinia pestis isolation (297), enzyme-linked immunosorbent assay, or both. Incidence was higher in males and young persons. Most buboes were inguinal, but children had a higher frequency of cervical or axillary buboes. Among laboratory-confirmed hospitalized patients, the case-fatality rate was 7.9%, although all Y. pestis isolates were sensitive to streptomycin, the recommended antibiotic. In this tropical city, plague outbreaks occur during the dry and cool season. Most cases are concentrated in the same crowded and unsanitary districts, a result of close contact among humans, rats, and shrews. Plague remains an important public health problem in Madagascar, and the potential is substantial for spread to other coastal cities and abroad.

  8. Epidemiologic Features of Four Successive Annual Outbreaks of Bubonic Plague in Mahajanga, Madagascar

    Science.gov (United States)

    Rahalison, Lila; Rasolomaharo, Monique; Ratsitorahina, Maherisoa; Mahafaly, Mahafaly; Razafimahefa, Maminirana; Duplantier, Jean-Marc; Ratsifasoamanana, Lala; Chanteau, Suzanne

    2002-01-01

    From 1995 to 1998, outbreaks of bubonic plague occurred annually in the coastal city of Mahajanga, Madagascar. A total of 1,702 clinically suspected cases of bubonic plague were reported, including 515 laboratory confirmed by Yersinia pestis isolation (297), enzyme-linked immunosorbent assay, or both. Incidence was higher in males and young persons. Most buboes were inguinal, but children had a higher frequency of cervical or axillary buboes. Among laboratory-confirmed hospitalized patients, the case-fatality rate was 7.9%, although all Y. pestis isolates were sensitive to streptomycin, the recommended antibiotic. In this tropical city, plague outbreaks occur during the dry and cool season. Most cases are concentrated in the same crowded and insanitary districts, a result of close contact among humans, rats, and shrews. Plague remains an important public health problem in Madagascar, and the potential is substantial for spread to other coastal cities and abroad. PMID:11927030

  9. The Thermoprecipitin Method in the Diagnosis of Bubonic Plague in Cadavers

    OpenAIRE

    Warner, Charlotte E.

    2017-01-01

    The diagnosis of bubonic plague in rat cadavers, the examination of which is a recognised method of prophylaxis for ships or other communities, which may have been in contact with endemic centres, is attended by especial difficulties, and, on the other hand, calls for especial speed and finality in technique

  10. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Directory of Open Access Journals (Sweden)

    Anne Derbise

    Full Text Available No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50 caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50. Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1- Y. pestis.VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single

  11. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

    Science.gov (United States)

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E

    2015-01-01

    No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral

  12. The Yfe and Feo transporters are involved in microaerobic growth and virulence of Yersinia pestis in bubonic plague.

    Science.gov (United States)

    Fetherston, Jacqueline D; Mier, Ildefonso; Truszczynska, Helena; Perry, Robert D

    2012-11-01

    The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, iron-limiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD(50)) relative to the Yfe(+) Feo(+) parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.

  13. Travel history key to picking up on signs of bubonic plague.

    Science.gov (United States)

    2015-11-01

    Health officials note an uptick in cases of bubonic plague in the United States this year, with at least 12 reported human cases reported since April 1. The CDC notes that healthcare providers should consider plague in patients who have traveled to plague-endemic areas and exhibit fever, headache, chills, weakness, and one or more swollen or tender and painful lymph nodes, referred to as buboes. Officials note that the disease rarely passes from person to person, but that this is a concern with patients who have developed the pneumonic form of the disease. Health officials note that in recent years there has been an average of seven cases of human plague each year in the United States, and that most of these cases are the bubonic form of the illness. Four patients confirmed to have plague this year have died, including the most recent case, a Utah man in his 70s. Most cases of plague in the United States occur in two regions. The first includes northern New Mexico, northern Arizona, and southern Colorado, and the second includes California, southern Oregon, and far western Nevada. When plague is suspected, treatment with antibiotics should begin immediately.

  14. Immunogenicity and protective immunity against bubonic plague and pneumonic plague by immunization of mice with the recombinant V10 antigen, a variant of LcrV.

    Science.gov (United States)

    DeBord, Kristin L; Anderson, Deborah M; Marketon, Melanie M; Overheim, Katie A; DePaolo, R William; Ciletti, Nancy A; Jabri, Bana; Schneewind, Olaf

    2006-08-01

    In contrast to Yersinia pestis LcrV, the recombinant V10 (rV10) variant (lacking residues 271 to 300) does not suppress the release of proinflammatory cytokines by immune cells. Immunization with rV10 generates robust antibody responses that protect mice against bubonic plague and pneumonic plague, suggesting that rV10 may serve as an improved plague vaccine.

  15. [Francisco Gavaldá, ahead of his time in the social statistics study of bubonic plague (1679)].

    Science.gov (United States)

    López Piñero, José María

    2006-01-01

    In 1651, Francisco Gavaldá (1618-1686) authored the first social statistics study on the bubonic plague which scourged western Europe in the mid-seventeenth century. specifically the plague having racked Valencia in 1647. Gavaldá was, in fact the first to study the plague not only statistically, but also from a social standpoint, denouncing the fact that it especially affected the poor, totally independently of the interests of the powerful.

  16. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

    Full Text Available Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN and gentamicin (GEN combination therapy with that of each antibiotic administered alone (i against Yersinia pestis in vitro and (ii in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h. In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen in surviving mice in each of the three groups. The median lymph node log(10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04 or CIN+GEN (5.8 vs. 2.8, p = 0.01. Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  17. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Science.gov (United States)

    Lemaître, Nadine; Ricard, Isabelle; Pradel, Elizabeth; Foligné, Benoît; Courcol, René; Simonet, Michel; Sebbane, Florent

    2012-01-01

    Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN) and gentamicin (GEN) combination therapy with that of each antibiotic administered alone (i) against Yersinia pestis in vitro and (ii) in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h). In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen) in surviving mice in each of the three groups. The median lymph node log(10) CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04) or CIN+GEN (5.8 vs. 2.8, p = 0.01). Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  18. RovA, a global regulator of Yersinia pestis, specifically required for bubonic plague.

    Science.gov (United States)

    Cathelyn, Jason S; Crosby, Seth D; Lathem, Wyndham W; Goldman, William E; Miller, Virginia L

    2006-09-05

    The pathogenic species of Yersinia contain the transcriptional regulator RovA. In Yersinia pseudotuberculosis and Yersinia enterocolitica, RovA regulates expression of the invasion factor invasin (inv), which mediates translocation across the intestinal epithelium. A Y. enterocolitica rovA mutant has a significant decrease in virulence by LD(50) analysis and an altered rate of dissemination compared with either wild type or an inv mutant, suggesting that RovA regulates multiple virulence factors. Here, we show the involvement of RovA in the virulence of Yersinia pestis, which naturally lacks a functional inv gene. A Y. pestis DeltarovA mutant is attenuated approximately 80-fold by LD(50) and is defective in dissemination/colonization of spleens and lungs after s.c. inoculation. However, the DeltarovA mutant is only slightly attenuated when given via an intranasal or i.p. route, indicating a more important role for RovA in bubonic plague than pneumonic plague or systemic infection. Microarray analysis was used to define the RovA regulon. The psa locus was among the most highly down-regulated loci in the DeltarovA mutant. A DeltapsaA mutant had a significant dissemination defect after s.c. infection but only slight attenuation by the pneumonic-disease model, closely mimicking the virulence defect seen with the DeltarovA mutant. DNA-binding studies revealed that RovA specifically interacts with the psaE and psaA promoter regions, indicating a direct role for RovA in regulating this locus. Thus, RovA appears to be a global transcription factor in Y. pestis and, through its regulatory influence on genes such as psaEFABC, contributes to the virulence of Y. pestis.

  19. THE BUBONIC PLAGUE OF 1349, THE WAGE-TO-RENT RATIO, AND THE ENGLISH PEASANT FAMILY

    Directory of Open Access Journals (Sweden)

    Stephanie O. Crofton

    2005-01-01

    Full Text Available The bubonic plague that swept England in 1349 provides an example of how changes in economic conditions can change norms of social behavior. The death of almost 50 percent of the population altered the returns to labor and land. As the demand for land and the supply of labor declined, rents fell and wages rose. This increased wage-to-rent ratio shifted the structure of the economy from household production to market production. In turn, these changes affected migration, family and community ties, women s labor force participation, family size, inheritance customs, the status of landowning widows, and care for the elderly.

  20. yadBC of Yersinia pestis, a new virulence determinant for bubonic plague.

    Science.gov (United States)

    Forman, Stanislav; Wulff, Christine R; Myers-Morales, Tanya; Cowan, Clarissa; Perry, Robert D; Straley, Susan C

    2008-02-01

    In all Yersinia pestis strains examined, the adhesin/invasin yadA gene is a pseudogene, yet Y. pestis is invasive for epithelial cells. To identify potential surface proteins that are structurally and functionally similar to YadA, we searched the Y. pestis genome for open reading frames with homology to yadA and found three: the bicistronic operon yadBC (YPO1387 and YPO1388 of Y. pestis CO92; y2786 and y2785 of Y. pestis KIM5), which encodes two putative surface proteins, and YPO0902, which lacks a signal sequence and likely is nonfunctional. In this study we characterized yadBC regulation and tested the importance of this operon for Y. pestis adherence, invasion, and virulence. We found that loss of yadBC caused a modest loss of invasiveness for epithelioid cells and a large decrease in virulence for bubonic plague but not for pneumonic plague in mice.

  1. Development and testing of a rapid diagnostic test for bubonic and pneumonic plague.

    Science.gov (United States)

    Chanteau, Suzanne; Rahalison, Lila; Ralafiarisoa, Lalao; Foulon, Jeanine; Ratsitorahina, Mahery; Ratsifasoamanana, Lala; Carniel, Elisabeth; Nato, Farida

    2003-01-18

    Plague is often fatal without prompt and appropriate treatment. It affects mainly poor and remote populations. Late diagnosis is one of the major causes of human death and spread of the disease, since it limits the effectiveness of control measures. We aimed to develop and assess a rapid diagnostic test (RDT) for plague. We developed a test that used monoclonal antibodies to the F1 antigen of Yersinia pestis. Sensitivity and specificity were assessed with a range of bacterial cultures and clinical samples, and compared with findings from available ELISA and bacteriological tests for plague. Samples from patients thought to have plague were tested with the RDT in the laboratory and by health workers in 26 pilot sites in Madagascar. The RDT detected concentrations of F1 antigen as low as 0.5 ng/mL in up to 15 min, and had a shelf life of 21 days at 60 degrees C. Its sensitivity and specificity were both 100%. RDT detected 41.6% and 31% more positive clinical specimens than did bacteriological methods and ELISA, respectively. The agreement rate between tests done at remote centres and in the laboratory was 89.8%. With the combination of bacteriological methods and F1 ELISA as reference standard, the positive and negative predictive values of the RDT were 90.6% and 86.7%, respectively. Our RDT is a specific, sensitive, and reliable test that can easily be done by health workers at the patient's bedside, for the rapid diagnosis of pneumonic and bubonic plague. This test will be of key importance for the control of plague in endemic countries.

  2. T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.

    Science.gov (United States)

    Levy, Yinon; Flashner, Yehuda; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Lazar, Shirley; Gur, David; Shafferman, Avigdor; Mamroud, Emanuelle

    2011-09-16

    Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague.

    Science.gov (United States)

    Sebbane, Florent; Jarrett, Clayton O; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

    2006-04-04

    Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.

  4. Oral Vaccination against Bubonic Plague Using a Live Avirulent Yersinia pseudotuberculosis Strain ▿

    Science.gov (United States)

    Blisnick, Thierry; Ave, Patrick; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

    2008-01-01

    We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague. PMID:18505804

  5. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain.

    Science.gov (United States)

    Blisnick, Thierry; Ave, Patrick; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2008-08-01

    We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague.

  6. Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague.

    Science.gov (United States)

    Sebbane, Florent; Lemaître, Nadine; Sturdevant, Daniel E; Rebeil, Roberto; Virtaneva, Kimmo; Porcella, Stephen F; Hinnebusch, B Joseph

    2006-08-01

    Yersinia pestis causes bubonic plague, characterized by an enlarged, painful lymph node, termed a bubo, that develops after bacterial dissemination from a fleabite site. In susceptible animals, the bacteria rapidly escape containment in the lymph node, spread systemically through the blood, and produce fatal sepsis. The fulminant progression of disease has been largely ascribed to the ability of Y. pestis to avoid phagocytosis and exposure to antimicrobial effectors of innate immunity. In vivo microarray analysis of Y. pestis gene expression, however, revealed an adaptive response to nitric oxide (NO)-derived reactive nitrogen species and to iron limitation in the extracellular environment of the bubo. Polymorphonuclear neutrophils recruited to the infected lymph node expressed abundant inducible NO synthase, and several Y. pestis homologs of genes involved in the protective response to reactive nitrogen species were up-regulated in the bubo. Mutation of one of these genes, which encodes the Hmp flavohemoglobin that detoxifies NO, attenuated virulence. Thus, the ability of Y. pestis to destroy immune cells and remain extracellular in the bubo appears to limit exposure to some but not all innate immune effectors. High NO levels induced during plague may also influence the developing adaptive immune response and contribute to septic shock.

  7. Braun lipoprotein (Lpp) contributes to virulence of yersiniae: potential role of Lpp in inducing bubonic and pneumonic plague.

    Science.gov (United States)

    Sha, Jian; Agar, Stacy L; Baze, Wallace B; Olano, Juan P; Fadl, Amin A; Erova, Tatiana E; Wang, Shaofei; Foltz, Sheri M; Suarez, Giovanni; Motin, Vladimir L; Chauhan, Sadhana; Klimpel, Gary R; Peterson, Johnny W; Chopra, Ashok K

    2008-04-01

    Yersinia pestis evolved from Y. pseudotuberculosis to become the causative agent of bubonic and pneumonic plague. We identified a homolog of the Salmonella enterica serovar Typhimurium lipoprotein (lpp) gene in Yersinia species and prepared lpp gene deletion mutants of Y. pseudotuberculosis YPIII, Y. pestis KIM/D27 (pigmentation locus minus), and Y. pestis CO92 with reduced virulence. Mice injected via the intraperitoneal route with 5 x 10(7) CFU of the Deltalpp KIM/D27 mutant survived a month, even though this would have constituted a lethal dose for the parental KIM/D27 strain. Subsequently, these Deltalpp KIM/D27-injected mice were solidly protected against an intranasally administered, highly virulent Y. pestis CO92 strain when it was given as five 50% lethal doses (LD(50)). In a parallel study with the pneumonic plague mouse model, after 72 h postinfection, the lungs of animals infected with wild-type (WT) Y. pestis CO92 and given a subinhibitory dose of levofloxacin had acute inflammation, edema, and masses of bacteria, while the lung tissue appeared essentially normal in mice inoculated with the Deltalpp mutant of CO92 and given the same dose of levofloxacin. Importantly, while WT Y. pestis CO92 could be detected in the bloodstreams and spleens of infected mice at 72 h postinfection, the Deltalpp mutant of CO92 could not be detected in those organs. Furthermore, the levels of cytokines/chemokines detected in the sera were significantly lower in animals infected with the Deltalpp mutant than in those infected with WT CO92. Additionally, the Deltalpp mutant was more rapidly killed by macrophages than was the WT CO92 strain. These data provided evidence that the Deltalpp mutants of yersiniae were significantly attenuated and could be useful tools in the development of new vaccines.

  8. Detection of Yersinia pestis using real-time PCR in patients with suspected bubonic plague.

    Science.gov (United States)

    Riehm, Julia M; Rahalison, Lila; Scholz, Holger C; Thoma, Bryan; Pfeffer, Martin; Razanakoto, Léa Mamiharisoa; Al Dahouk, Sascha; Neubauer, Heinrich; Tomaso, Herbert

    2011-02-01

    Yersinia (Y.) pestis, the causative agent of plague, is endemic in natural foci of Asia, Africa, and America. Real-time PCR assays have been described as rapid diagnostic tools, but so far none has been validated for its clinical use. In a retrospective clinical study we evaluated three real-time PCR assays in two different assay formats, 5'-nuclease and hybridization probes assays. Lymph node aspirates from 149 patients from Madagascar with the clinical diagnosis of bubonic plague were investigated for the detection of Y. pestis DNA. Results of real-time PCR assays targeting the virulence plasmids pPCP1 (pla gene), and pMT1 (caf1, Ymt genes) were compared with an F1-antigen immunochromatographic test (ICT) and cultivation of the organism. Out of the 149 samples an infection with Y. pestis was confirmed by culture in 47 patients while ICT was positive in 88 including all culture proven cases. The best real-time PCR assay was the 5'-nuclease assay targeting pla which was positive in 120 cases. In conclusion, the 5'-nuclease assay targeting pla can be recommended as diagnostic tool for establishing a presumptive diagnosis when bubonic plague is clinically suspected. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Characterization of an F1 Deletion Mutant of Yersinia pestis CO92, Pathogenic Role of F1 Antigen in Bubonic and Pneumonic Plague, and Evaluation of Sensitivity and Specificity of F1 Antigen Capture-Based Dipsticks▿

    Science.gov (United States)

    Sha, Jian; Endsley, Janice J.; Kirtley, Michelle L.; Foltz, Sheri M.; Huante, Matthew B.; Erova, Tatiana E.; Kozlova, Elena V.; Popov, Vsevolod L.; Yeager, Linsey A.; Zudina, Irina V.; Motin, Vladimir L.; Peterson, Johnny W.; DeBord, Kristin L.; Chopra, Ashok K.

    2011-01-01

    We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with Yersinia pestis CO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Δcaf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Δcaf mutant was devoid of a capsule. The growth rate of the Δcaf mutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37°C, although the mutant's growth dropped slightly during the late phase at 37°C. The Δcaf mutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 μg/ml of purified F1 antigen or 1 × 105 to 5 × 105 CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 × 108 CFU/ml of the Δcaf mutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains of Y. pestis in bubonic and pneumonic plague. PMID:21367990

  10. Imaging of bubonic plague dynamics by in vivo tracking of bioluminescent Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Toan Nham

    Full Text Available Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba, followed by a colonization of the draining inguinal lymph node(s, and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response.

  11. Imaging of bubonic plague dynamics by in vivo tracking of bioluminescent Yersinia pestis.

    Science.gov (United States)

    Nham, Toan; Filali, Sofia; Danne, Camille; Derbise, Anne; Carniel, Elisabeth

    2012-01-01

    Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI) to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba), followed by a colonization of the draining inguinal lymph node(s), and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response.

  12. Zinc transporters YbtX and ZnuABC are required for the virulence of Yersinia pestis in bubonic and pneumonic plague in mice.

    Science.gov (United States)

    Bobrov, Alexander G; Kirillina, Olga; Fosso, Marina Y; Fetherston, Jacqueline D; Miller, M Clarke; VanCleave, Tiva T; Burlison, Joseph A; Arnold, William K; Lawrenz, Matthew B; Garneau-Tsodikova, Sylvie; Perry, Robert D

    2017-06-21

    A number of bacterial pathogens require the ZnuABC Zinc (Zn2+) transporter and/or a second Zn2+ transport system to overcome Zn2+ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn2+ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn2+ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic plague while a ybtX mutant retains high virulence in both plague models. While sequestration of host Zn is a key nutritional immunity factor, excess Zn appears to have a significant antimicrobial role in controlling intracellular bacterial survival. Here, we demonstrate that ZntA, a Zn2+ exporter, plays a role in resistance to Zn toxicity in vitro, but that a zntA zur double mutant retains high virulence in both pneumonic and bubonic plague models and survival in macrophages. We also confirm that Ybt does not directly bind Zn2+in vitro under the conditions tested. However, we detect a significant increase in Zn2+-binding ability of filtered supernatants from a Ybt+ strain compared to those from a strain unable to produce the siderophore, supporting our previously published data that Ybt biosynthetic genes are involved in the production of a secreted Zn-binding molecule (zincophore). Our data suggest that Ybt or a modified Ybt participate in or promote Zn-binding activity in culture supernatants and is involved in Zn acquisition in Y. pestis.

  13. A Toll/interleukin (IL)-1 receptor domain protein from Yersinia pestis interacts with mammalian IL-1/Toll-like receptor pathways but does not play a central role in the virulence of Y. pestis in a mouse model of bubonic plague.

    Science.gov (United States)

    Spear, Abigail M; Rana, Rohini R; Jenner, Dominic C; Flick-Smith, Helen C; Oyston, Petra C F; Simpson, Peter; Matthews, Stephen J; Byrne, Bernadette; Atkins, Helen S

    2012-06-01

    The Toll/interleukin (IL)-1 receptor (TIR) domain is an essential component of eukaryotic innate immune signalling pathways. Interaction between TIR domains present in Toll-like receptors and associated adaptors initiates and propagates an immune signalling cascade. Proteins containing TIR domains have also been discovered in bacteria. Studies have subsequently shown that these proteins are able to modulate mammalian immune signalling pathways dependent on TIR interactions and that this may represent an evasion strategy for bacterial pathogens. Here, we investigate a TIR domain protein from the highly virulent bacterium Yersinia pestis, the causative agent of plague. When overexpressed in vitro this protein is able to downregulate IL-1β- and LPS-dependent signalling to NFκB and to interact with the TIR adaptor protein MyD88. This interaction is dependent on a single proline residue. However, a Y. pestis knockout mutant lacking the TIR domain protein was not attenuated in virulence in a mouse model of bubonic plague. Minor alterations in the host cytokine response to the mutant were indicated, suggesting a potential subtle role in pathogenesis. The Y. pestis mutant also showed increased auto-aggregation and reduced survival in high-salinity conditions, phenotypes which may contribute to pathogenesis or survival.

  14. Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques.

    Science.gov (United States)

    Zhang, Qingwen; Wang, Qiong; Tian, Guang; Qi, Zhizhen; Zhang, Xuecan; Wu, Xiaohong; Qiu, Yefeng; Bi, Yujing; Yang, Xiaoyan; Xin, Youquan; He, Jian; Zhou, Jiyuan; Zeng, Lin; Yang, Ruifu; Wang, Xiaoyi

    2014-01-01

    Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain's protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge.

  15. Characterization of the rat pneumonic plague model: infection kinetics following aerosolization of Yersinia pestis CO92.

    Science.gov (United States)

    Agar, Stacy L; Sha, Jian; Foltz, Sheri M; Erova, Tatiana E; Walberg, Kristin G; Baze, Wallace B; Suarez, Giovanni; Peterson, Johnny W; Chopra, Ashok K

    2009-02-01

    Yersinia pestis, the causative agent of human bubonic and pneumonic plague, is spread during natural infection by the fleas of rodents. Historically associated with infected rat fleas, studies on the kinetics of infection in rats are surprisingly few, and these reports have focused mainly on bubonic plague. Although the natural route of primary infection results in bubonic plague in humans, it is commonly thought that aerosolized Y. pestis will be utilized during a biowarfare attack. Accordingly, based on our previous characterization of the mouse model of pneumonic plague, we sought to examine the progression of infection in rats exposed in a whole-body Madison chamber to aerosolized Y. pestis CO92. Following an 8.6 LD(50) dose of Y. pestis, injury was apparent in the rat tissues based on histopathology, and chemokines and cytokines rose above control levels (1h post infection [p.i.]) in the sera and organ homogenates over a 72-h infection period. Bacteria disseminated from the lungs to peripheral organs, with the largest increases in the spleen, followed by the liver and blood at 72h p.i. compared to the 1h controls. Importantly, rats were as sensitive to pneumonic plague as mice, having a similar LD(50) dose by the intranasal and aerosolized routes. Further, we showed direct transmission of plague bacteria from infected to uninfected rats. Taken together, the data allowed us to characterize for the first time a rat pneumonic plague model following aerosolization of Y. pestis.

  16. Yersinia pestis Yop secretion protein F: purification, characterization, and protective efficacy against bubonic plague.

    Science.gov (United States)

    Swietnicki, Wieslaw; Powell, Bradford S; Goodin, Jeremy

    2005-07-01

    Yersinia pestis is a gram-negative human pathogen that uses a type III secretion system to deliver virulence factors into human hosts. The delivery is contact-dependent and it has been proposed that polymerization of Yop secretion protein F (YscF) is used to puncture mammalian cell membranes to facilitate delivery of Yersinia outer protein effectors into host cells. To evaluate the potential immunogenicity and protective efficacy of YscF against Y. pestis, we used a purified recombinant YscF protein as a potential vaccine candidate in a mouse subcutaneous infection model. YscF was expressed and purified from Escherichia coli by immobilized metal-ion affinity chromatography and protein identity was confirmed by ion trap mass spectrometry. The recombinant protein was highly alpha-helical and formed relatively stable aggregates under physiological conditions. The properties were consistent with behavior expected for the native YscF, suggesting that the antigen was properly folded. Ten mice were inoculated subcutaneously, administered booster injections after one month, and challenged with 130 LD(50) of wild type Y. pestis CO92. Six animals in the vaccinated group but none in the control group survived the challenge. The vaccinated animals produced high levels of specific antibodies against YscF as determined by Western blot. The data were statistically significant (P = 0.053 by two-tailed Fisher's test), suggesting that the YscF protein can provide a protective immune response against lethal plague challenge during subcutaneous plague infection.

  17. Characterization of an F1 deletion mutant of Yersinia pestis CO92, pathogenic role of F1 antigen in bubonic and pneumonic plague, and evaluation of sensitivity and specificity of F1 antigen capture-based dipsticks.

    Science.gov (United States)

    Sha, Jian; Endsley, Janice J; Kirtley, Michelle L; Foltz, Sheri M; Huante, Matthew B; Erova, Tatiana E; Kozlova, Elena V; Popov, Vsevolod L; Yeager, Linsey A; Zudina, Irina V; Motin, Vladimir L; Peterson, Johnny W; DeBord, Kristin L; Chopra, Ashok K

    2011-05-01

    We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with Yersinia pestis CO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Δcaf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Δcaf mutant was devoid of a capsule. The growth rate of the Δcaf mutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37 °C, although the mutant's growth dropped slightly during the late phase at 37 °C. The Δcaf mutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 μg/ml of purified F1 antigen or 1 × 10(5) to 5 × 10(5) CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 × 10(8) CFU/ml of the Δcaf mutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains of Y. pestis in bubonic and pneumonic plague.

  18. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice.

    Science.gov (United States)

    Alvarez, M Lucrecia; Pinyerd, Heidi L; Crisantes, Jason D; Rigano, M Manuela; Pinkhasov, Julia; Walmsley, Amanda M; Mason, Hugh S; Cardineau, Guy A

    2006-03-24

    Yersinia pestis, the causative agent of plague, is an extremely virulent bacterium but there are no approved vaccines for protection against it. Our goal was to produce a vaccine that would address: ease of delivery, mucosal efficacy, safety, rapid scalability, and cost. We developed a novel production and delivery system for a plague vaccine of a Y. pestis F1-V antigen fusion protein expressed in tomato. Immunogenicity of the F1-V transgenic tomatoes was confirmed in mice that were primed subcutaneously with bacterially-produced F1-V and boosted orally with transgenic tomato fruit. Expression of the plague antigens in fruit allowed producing an oral vaccine candidate without protein purification and with minimal processing technology.

  19. A novel autotransporter adhesin is required for efficient colonization during bubonic plague.

    Science.gov (United States)

    Lawrenz, Matthew B; Lenz, Jonathan D; Miller, Virginia L

    2009-01-01

    Many proteins secreted by the type V secretion system (autotransporters) have been linked to virulence in gram-negative bacteria. Several putative conventional autotransporters are present in the Yersinia pestis genome, but only one, YapE, is conserved in the other pathogenic Yersinia species. Here, we introduce YapE and demonstrate that it is secreted via a type V mechanism. Inactivation of yapE in Y. pestis results in decreased efficiency in colonization of tissues during bubonic infection. Coinfection with wild-type bacteria only partially compensates for this defect. Analysis of the host immune response suggests that YapE is required for either efficient colonization at the inoculation site or dissemination to draining lymph nodes. YapE also demonstrates adhesive properties capable of mediating interactions with bacteria and eukaryotic cells. These findings support a role for YapE in modulating host-pathogen interactions that are important for colonization of the mammalian host.

  20. Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague.

    Science.gov (United States)

    Yang, Xinghong; Hinnebusch, B Joseph; Trunkle, Theresa; Bosio, Catharine M; Suo, Zhiyong; Tighe, Mike; Harmsen, Ann; Becker, Todd; Crist, Kathryn; Walters, Nancy; Avci, Recep; Pascual, David W

    2007-01-15

    The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.

  1. A three-variable chaotic system for the epidemic of bubonic plague in Bombay by the end of the 19th century and its coupling to the epizootics of the two main species of rats

    Science.gov (United States)

    Mangiarotti, Sylvain

    2016-04-01

    A plague epidemic broke out in Bombay by the end of the 19th century. A committee was first appointed by the Bombay City [1] in order to stop the epidemic before the rain season started. Unfortunately, the disease could not be stopped and the epidemic became endemic. After several years, another Advisory Committee [2] was appointed that tried to investigate the causes of plague in all possible directions. An impressing quantity of information was gathered during the period 1907-1911 and published. In particular, it was noticed that the epidemic was systematically preceded by epizootics of rats. For this reason, the populations of the main species of rodents were systematically monitored. This data set is revisited here by using a multivariate version of the global modeling technique [3]. The aim of this technique is to obtain a set of Ordinary Differential Equations directly from time series. Three observational time series are considered: the number of person died of bubonic plague per half month (1), and the number of captured infected black rats Mus rattus (2) and brown rats Mus decumanus (3). Several models are obtained, all based on the same algebraic basic structure. These models are, either directly chaotic, or close to chaos (chaos could easily be obtained by tuning one model parameter). The algebraic structure of the simplest model obtained is analyzed in more details. Surprisingly, it is found that the interpretation of the coupling between the three variables can be done term by term. This interpretation is in quite good coherence with the conclusions of the Advisory Committee published one hundred years ago. This structure also shows that the human action to slow down the disease during this period was obviously effective, although insufficient to stop the epidemic drastically. This result suggests that the global modeling technique can be a powerful tool to detect causal couplings in epidemiology, and, more generally, among observational variables from

  2. Diagnosis of bubonic plague by PCR in Madagascar under field conditions.

    Science.gov (United States)

    Rahalison, L; Vololonirina, E; Ratsitorahina, M; Chanteau, S

    2000-01-01

    The diagnostic value of a PCR assay that amplifies a 501-bp fragment of the Yersinia pestis caf1 gene has been determined in a reference laboratory with 218 bubo aspirates collected from patients with clinically suspected plague managed in a regional hospital in Madagascar. The culture of Y. pestis and the detection of the F1 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) were used as reference diagnostic methods. The sensitivity of PCR was 89% (57 of 64) for the Y. pestis-positive patients, and 80.7% (63 of 78) for the F1 Ag-positive patients. The specificity of PCR for the culture-, F1 Ag-, and antibody-negative patients (n = 105) was 100%. Because in Madagascar most patients with plague are managed and their clinical samples are collected in remote villages, the usefulness of PCR was evaluated for routine diagnostic use in the operational conditions of the control program. The sensitivity of PCR was 50% (25 of 50) relative to the results of culture and 35.2% (19 of 54) relative to the results of the F1 Ag immunocapture ELISA. The specificity of PCR under these conditions was 96%. In conclusion, the PCR method was found to be very specific but not as sensitive as culture or the F1 Ag detection method. The limitation in sensitivity may have been due to suboptimal field conditions and the small volumes of samples used for DNA extraction. This technique is not recommended as a routine diagnostic test for plague in Madagascar.

  3. Diagnosis of Bubonic Plague by PCR in Madagascar under Field Conditions

    Science.gov (United States)

    Rahalison, L.; Vololonirina, E.; Ratsitorahina, M.; Chanteau, S.

    2000-01-01

    The diagnostic value of a PCR assay that amplifies a 501-bp fragment of the Yersinia pestis caf1 gene has been determined in a reference laboratory with 218 bubo aspirates collected from patients with clinically suspected plague managed in a regional hospital in Madagascar. The culture of Y. pestis and the detection of the F1 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) were used as reference diagnostic methods. The sensitivity of PCR was 89% (57 of 64) for the Y. pestis-positive patients, and 80.7% (63 of 78) for the F1 Ag-positive patients. The specificity of PCR for the culture-, F1 Ag-, and antibody-negative patients (n = 105) was 100%. Because in Madagascar most patients with plague are managed and their clinical samples are collected in remote villages, the usefulness of PCR was evaluated for routine diagnostic use in the operational conditions of the control program. The sensitivity of PCR was 50% (25 of 50) relative to the results of culture and 35.2% (19 of 54) relative to the results of the F1 Ag immunocapture ELISA. The specificity of PCR under these conditions was 96%. In conclusion, the PCR method was found to be very specific but not as sensitive as culture or the F1 Ag detection method. The limitation in sensitivity may have been due to suboptimal field conditions and the small volumes of samples used for DNA extraction. This technique is not recommended as a routine diagnostic test for plague in Madagascar. PMID:10618097

  4. Imaging early pathogenesis of bubonic plague: are neutrophils commandeered for lymphatic transport of bacteria?

    Science.gov (United States)

    Bland, David M; Anderson, Deborah M

    2013-11-05

    Vector-borne infections begin in the dermis when a pathogen is introduced by an arthropod during a blood meal. Several barriers separate an invading pathogen from its replicative niche, including phagocytic cells in the dermis that activate immunity by engulfing would-be pathogens and migrating to the lymph node. In addition, neutrophils circulating in the blood are rapidly recruited when the dermal barriers are penetrated. For flea-borne disease, no insect-encoded immune-suppressive molecules have yet been described that might influence the establishment of infection, leaving the bacteria on their own to defend against the mammalian immune system. Shortly after a flea transmits Yersinia pestis to a mammalian host, the bacteria are transported to the lymph node, where they grow logarithmically and later spread systemically. Even a single cell of Y. pestis can initiate a lethal case of plague. In their article, J. G. Shannon et al. [mBio 4(5):e00170-13, 2013, doi:10.1128/mBio.00170-13] used intravital microscopy to visualize trafficking of Y. pestis in transgenic mice in vivo, which allowed them to examine interactions between bacteria and specific immune cells. Bacteria appeared to preferentially interact with neutrophils but had no detectable interactions with dendritic cells. These findings suggest that Y. pestis infection of neutrophils not only prevents their activation but may even result in their return to circulation and migration to distal sites.

  5. Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine.

    Science.gov (United States)

    Elvin, Stephen J; Eyles, James E; Howard, Kenneth A; Ravichandran, Easwaran; Somavarappu, Satyanarayan; Alpar, H Oya; Williamson, E Diane

    2006-05-15

    Protection against virulent plague challenge by the parenteral and aerosol routes was afforded by a single administration of microencapsulated Caf1 and LcrV antigens from Yersinia pestis in BALB/c mice. Recombinant Caf1 and LcrV were individually encapsulated in polymeric microspheres, to the surface of which additional antigen was adsorbed. The microspheres containing either Caf1 or LcrV were blended and used to immunise mice on a single occasion, by either the intra-nasal or intra-muscular route. Both routes of immunisation induced systemic and local immune responses, with high levels of serum IgG being developed in response to both vaccine antigens. In Elispot assays, secretion of cytokines by spleen and draining lymph node cells was demonstrated, revealing activation of both Th1 and Th2 associated cytokines; and spleen cells from animals immunised by either route were found to proliferate in vitro in response to both vaccine antigens. Virulent challenge experiments demonstrated that non-invasive immunisation by intra-nasal instillation can provide strong systemic and local immune responses and protect against high level challenge. Microencapsulation of these vaccine antigens has the added advantage that controlled release of the antigens occurs in vivo, so that protective immunity can be induced after only a single immunising dose.

  6. Small todents fleas from the bubonic plague focus located in the Serra dos Órgãos Mountain Range, State of Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Raimundo Wilson de Carvalho

    2001-07-01

    Full Text Available Eleven species of fleas were collected from 601 small rodents, from November 1995 to October 1997, in areas of natural focus of bubonic plague, including the municipalities of Nova Friburgo, Sumidouro and Teresópolis, State of Rio de Janeiro, Brazil. Among 924 fleas collected, Polygenis (Polygenis rimatus (Rhopalopsyllidae was the predominant species regarding the frequency, representing 41.3% (N:382, followed by P. (Neopolygenis pradoi, representing 20% (N:185 and Craneopsylla minervaminerva (Stephanocircidae, representing 18.9% (N:175. The host Akodon cursor harbored 47.9% of these fleas. Other six host species were infested by 52.1% of the remaining fleas. Fleas were found on hosts and in places within the focus not previously reported by the literature.

  7. Human case of bubonic plague resulting from the bite of a wild Gunnison's prairie dog during translocation from a plague-endemic area.

    Science.gov (United States)

    Melman, S D; Ettestad, P E; VinHatton, E S; Ragsdale, J M; Takacs, N; Onischuk, L M; Leonard, P M; Master, S S; Lucero, V S; Kingry, L C; Petersen, J M

    2018-02-01

    Plague is a zoonotic disease (transmitted mainly by fleas and maintained in nature by rodents) that causes severe acute illness in humans. We present a human plague case who became infected by the bite of a wild Gunnison's prairie dog, and a good practical example of the One Health approach that resulted in a rapid public health response. The exposure occurred while the animal was being transported for relocation to a wildlife refuge after being trapped in a plague enzootic area. This is the first report of a human plague case resulting from the bite of a Gunnison's prairie dog. Additionally, we present an observation of a longer incubation period for plague in captive prairie dogs, leading to a recommendation for a longer quarantine period for prairie dogs during translocation efforts. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  8. SUCCESSFUL PLAGUE CONTROL IN NAMIBIA

    African Journals Online (AJOL)

    The number of plague cases in the early years of the disease in. Namibia has not been properly documented. Hospital records show that the overwhelming clinical form of plague is the bubonic plague, although cases of septicaemic plague have also been recorded. 0 cases of pneumonic plague have been confirmed.

  9. Human Plague Risk: Spatial-Temporal Models

    Science.gov (United States)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  10. Waldemar Mordecai Haffkine, CIE (1860-1930): prophylactic vaccination against cholera and bubonic plague in British India.

    Science.gov (United States)

    Hawgood, Barbara J

    2007-02-01

    Waldemar Mordecai Haffkine developed an anticholera vaccine at the Pasteur Institute, Paris, in 1892. From the results of field trials in India from 1893 to 1896, he has been credited as having carried out the first effective prophylactic vaccination for a bacterial disease in man. When the plague pandemic reached Bombay, Haffkine became bacteriologist to the Government of (British) India (1896-1915). He soon produced an effective antiplague vaccine and large inoculation schemes were commenced. In 1902 19 people in Mulkowal (Punjab) died from tetanus poisoning as a consequence of antiplague vaccination. Haffkine was blamed unjustly and exonerated only in 1907, following a campaign spear-headed by Ronald Ross. In India the stigma remained. In 1925 in tribute to the great bacteriologist, the Bombay Government renamed the laboratory as the Haffkine Institute. The Haffkine Biopharmaceutical Corporation Ltd and the Haffkine Institute for Training, Research and Testing in Mumbai continue to be important centres for public health.

  11. Role of the Yersinia pestis yersiniabactin iron acquisition system in the incidence of flea-borne plague.

    Directory of Open Access Journals (Sweden)

    Florent Sebbane

    2010-12-01

    Full Text Available Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.

  12. Role of the Yersinia pestis yersiniabactin iron acquisition system in the incidence of flea-borne plague.

    Science.gov (United States)

    Sebbane, Florent; Jarrett, Clayton; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

    2010-12-17

    Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.

  13. Empirical assessment of a threshold model for sylvatic plague

    DEFF Research Database (Denmark)

    Davis, Stephen; Leirs, Herwig; Viljugrein, H.

    2007-01-01

    Plague surveillance programmes established in Kazakhstan, Central Asia, during the previous century, have generated large plague archives that have been used to parameterize an abundance threshold model for sylvatic plague in great gerbil (Rhombomys opimus) populations. Here, we assess the model ...

  14. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

    Science.gov (United States)

    Mellado-Sanchez, Gabriela; Ramirez, Karina; Drachenberg, Cinthia B; Diaz-McNair, Jovita; Rodriguez, Ana L; Galen, James E; Nataro, James P; Pasetti, Marcela F

    2013-03-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Transcriptomic and Innate Immune Responses to Yersinia pestis in the Lymph Node during Bubonic Plague▿ †

    Science.gov (United States)

    Comer, Jason E.; Sturdevant, Daniel E.; Carmody, Aaron B.; Virtaneva, Kimmo; Gardner, Donald; Long, Dan; Rosenke, Rebecca; Porcella, Stephen F.; Hinnebusch, B. Joseph

    2010-01-01

    A delayed inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response to Y. pestis and how it is influenced by the Yersinia virulence plasmid (pYV). Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression or cytokine response by host lymph node cells in the developing bubo. Only after systemic spread had led to terminal septicemic plague was a transcriptomic response detected, which included upregulation of several cytokine, chemokine, and other immune response genes. Although an initial intracellular phase of Y. pestis infection has been postulated, a Th1-type cytokine response associated with classical activation of macrophages was not observed during the bubonic stage of disease. However, elevated levels of interleukin-17 (IL-17) were present in infected lymph nodes. In the absence of pYV, sustained recruitment to the lymph node of polymorphonuclear leukocytes (PMN, or neutrophils), the major IL-17 effector cells, correlated with clearance of infection. Thus, the ability to counteract a PMN response in the lymph node appears to be a major in vivo function of the Y. pestis virulence plasmid. PMID:20876291

  16. Thinking extreme social violence: the model of the literary plague.

    Science.gov (United States)

    Priel, Beatriz

    2007-12-01

    The author uses literary plagues as a model for thinking psychoanalytically about the basic anxieties activated among perpetrators of sanctioned massacres. The model of the plague allows abstracting an underlying primitive psychological organization characterized by syncretism and a powerful anxiety of de-differentiation and confusion, leading characteristically to imitative behavior within the in-group as well as to the disavowal of the out-group members similarities to oneself, i.e. the disavowal of the other's humanity. Recognizing the historical and social foundations of discrimination and genocide, the author analyzes the interaction between group and individual processes that allow ordinary people to join daily acts of immoral violence. She dramatizes the model of the plague through a psychoanalytic reading of three literary plagues: Thebes' plague according to Sophocles, Camus's chronicle of the plague in Oran, and Saramago's meditation on the plague of white blindness.

  17. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Science.gov (United States)

    Bozue, Joel; Cote, Christopher K; Chance, Taylor; Kugelman, Jeffrey; Kern, Steven J; Kijek, Todd K; Jenkins, Amy; Mou, Sherry; Moody, Krishna; Fritz, David; Robinson, Camenzind G; Bell, Todd; Worsham, Patricia

    2014-01-01

    Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  18. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Directory of Open Access Journals (Sweden)

    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  19. Role of the Yersinia pestis Ail Protein in Preventing a Protective Polymorphonuclear Leukocyte Response during Bubonic Plague▿

    Science.gov (United States)

    Hinnebusch, B. Joseph; Jarrett, Clayton O.; Callison, Julie A.; Gardner, Donald; Buchanan, Susan K.; Plano, Gregory V.

    2011-01-01

    The ability of Yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The Y. pestis ail mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in vitro. Intradermal infection with the ail mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive adaptive immune response was generated after high-dose challenge, as evidenced by high serum antibody levels against Y. pestis F1 antigen. The Y. pestis Ail protein is an important bubonic plague virulence factor that inhibits the innate immune response, in particular the recruitment of a protective PMN response to the infected lymph node. PMID:21969002

  20. The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague▿

    Science.gov (United States)

    Fetherston, Jacqueline D.; Kirillina, Olga; Bobrov, Alexander G.; Paulley, James T.; Perry, Robert D.

    2010-01-01

    Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an ∼24-fold-higher 50% lethal dose (LD50) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Δpgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague. PMID:20160020

  1. Plague: Clinics, Diagnosis and Treatment.

    Science.gov (United States)

    Nikiforov, Vladimir V; Gao, He; Zhou, Lei; Anisimov, Andrey

    2016-01-01

    Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.

  2. Plague in China 2014?All sporadic case report of pneumonic plague

    OpenAIRE

    Li, Yun-fang; Li, De-biao; Shao, Hong-sheng; Li, Hong-jun; Han, Yue-dong

    2016-01-01

    Background Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. Case presentation All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient spe...

  3. Roles of chaperone/usher pathways of Yersinia pestis in a murine model of plague and adhesion to host cells.

    Science.gov (United States)

    Hatkoff, Matthew; Runco, Lisa M; Pujol, Celine; Jayatilaka, Indralatha; Furie, Martha B; Bliska, James B; Thanassi, David G

    2012-10-01

    Yersinia pestis and many other Gram-negative pathogenic bacteria use the chaperone/usher (CU) pathway to assemble virulence-associated surface fibers termed pili or fimbriae. Y. pestis has two well-characterized CU pathways: the caf genes coding for the F1 capsule and the psa genes coding for the pH 6 antigen. The Y. pestis genome contains additional CU pathways that are capable of assembling pilus fibers, but the roles of these pathways in the pathogenesis of plague are not understood. We constructed deletion mutations in the usher genes for six of the additional Y. pestis CU pathways. The wild-type (WT) and usher deletion strains were compared in the murine bubonic (subcutaneous) and pneumonic (intranasal) plague infection models. Y. pestis strains containing deletions in CU pathways y0348-0352, y1858-1862, and y1869-1873 were attenuated for virulence compared to the WT strain by the intranasal, but not subcutaneous, routes of infection, suggesting specific roles for these pathways during pneumonic plague. We examined binding of the Y. pestis WT and usher deletion strains to A549 human lung epithelial cells, HEp-2 human cervical epithelial cells, and primary human and murine macrophages. Y. pestis CU pathways y0348-0352 and y1858-1862 were found to contribute to adhesion to all host cells tested, whereas pathway y1869-1873 was specific for binding to macrophages. The correlation between the virulence attenuation and host cell binding phenotypes of the usher deletion mutants identifies three of the additional CU pathways of Y. pestis as mediating interactions with host cells that are important for the pathogenesis of plague.

  4. Climatically driven synchrony of gerbil populations allows large-scale plague outbreaks.

    Science.gov (United States)

    Kausrud, Kyrre Linné; Viljugrein, Hildegunn; Frigessi, Arnoldo; Begon, Mike; Davis, Stephen; Leirs, Herwig; Dubyanskiy, Vladimir; Stenseth, Nils Chr

    2007-08-22

    In central Asia, the great gerbil (Rhombomys opimus) is the main host for the bacterium Yersinia pestis, the cause of bubonic plague. In order to prevent plague outbreaks, monitoring of the great gerbil has been carried out in Kazakhstan since the late 1940s. We use the resulting data to demonstrate that climate forcing synchronizes the dynamics of gerbils over large geographical areas. As it is known that gerbil densities need to exceed a threshold level for plague to persist, synchrony in gerbil abundance across large geographical areas is likely to be a condition for plague outbreaks at similar large scales. Here, we substantiate this proposition through autoregressive modelling involving the normalized differentiated vegetation index as a forcing covariate. Based upon predicted climate changes, our study suggests that during the next century, plague epizootics may become more frequent in central Asia.

  5. Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

    Science.gov (United States)

    Quenee, Lauriane E.; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-01-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration–approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. PMID:21406168

  6. Plague in Guinea pigs and its prevention by subunit vaccines.

    Science.gov (United States)

    Quenee, Lauriane E; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-04-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Cethromycin-Mediated Protection against the Plague Pathogen Yersinia pestis in a Rat Model of Infection and Comparison with Levofloxacin ▿

    Science.gov (United States)

    Rosenzweig, Jason A.; Brackman, Sheri M.; Kirtley, Michelle L.; Sha, Jian; Erova, Tatiana E.; Yeager, Linsey A.; Peterson, Johnny W.; Xu, Ze-Qi; Chopra, Ashok K.

    2011-01-01

    The Gram-negative plague bacterium, Yersinia pestis, has historically been regarded as one of the deadliest pathogens known to mankind, having caused three major pandemics. After being transmitted by the bite of an infected flea arthropod vector, Y. pestis can cause three forms of human plague: bubonic, septicemic, and pneumonic, with the latter two having very high mortality rates. With increased threats of bioterrorism, it is likely that a multidrug-resistant Y. pestis strain would be employed, and, as such, conventional antibiotics typically used to treat Y. pestis (e.g., streptomycin, tetracycline, and gentamicin) would be ineffective. In this study, cethromycin (a ketolide antibiotic which inhibits bacterial protein synthesis and is currently in clinical trials for respiratory tract infections) was evaluated for antiplague activity in a rat model of pneumonic infection and compared with levofloxacin, which operates via inhibition of bacterial topoisomerase and DNA gyrase. Following a respiratory challenge of 24 to 30 times the 50% lethal dose of the highly virulent Y. pestis CO92 strain, 70 mg of cethromycin per kg of body weight (orally administered twice daily 24 h postinfection for a period of 7 days) provided complete protection to animals against mortality without any toxic effects. Further, no detectable plague bacilli were cultured from infected animals' blood and spleens following cethromycin treatment. The antibiotic was most effective when administered to rats 24 h postinfection, as the animals succumbed to infection if treatment was further delayed. All cethromycin-treated survivors tolerated 2 subsequent exposures to even higher lethal Y. pestis doses without further antibiotic treatment, which was related, in part, to the development of specific antibodies to the capsular and low-calcium-response V antigens of Y. pestis. These data demonstrate that cethromycin is a potent antiplague drug that can be used to treat pneumonic plague. PMID:21859946

  8. Testing the generality of a trophic-cascade model for plague

    Science.gov (United States)

    Collinge, S.K.; Johnson, W.C.; Ray, C.; Matchett, R.; Grensten, J.; Cully, J.F.; Gage, K.L.; Kosoy, M.Y.; Loye, J.E.; Martin, A.P.

    2005-01-01

    Climate may affect the dynamics of infectious diseases by shifting pathogen, vector, or host species abundance, population dynamics, or community interactions. Black-tailed prairie dogs (Cynomys ludovicianus) are highly susceptible to plague, yet little is known about factors that influence the dynamics of plague epizootics in prairie dogs. We investigated temporal patterns of plague occurrence in black-tailed prairie dogs to assess the generality of links between climate and plague occurrence found in previous analyses of human plague cases. We examined long-term data on climate and plague occurrence in prairie dog colonies within two study areas. Multiple regression analyses revealed that plague occurrence in prairie dogs was not associated with climatic variables in our Colorado study area. In contrast, plague occurrence was strongly associated with climatic variables in our Montana study area. The models with most support included a positive association with precipitation in April-July of the previous year, in addition to a positive association with the number of "warm" days and a negative association with the number of "hot" days in the same year as reported plague events. We conclude that the timing and magnitude of precipitation and temperature may affect plague occurrence in some geographic areas. The best climatic predictors of plague occurrence in prairie dogs within our Montana study area are quite similar to the best climatic predictors of human plague cases in the southwestern United States. This correspondence across regions and species suggests support for a (temperature-modulated) trophic-cascade model for plague, including climatic effects on rodent abundance, flea abundance, and pathogen transmission, at least in regions that experience strong climatic signals. ?? 2005 EcoHealth Journal Consortium.

  9. Evaluation of Protective Potential of Yersinia pestis Outer Membrane Protein Antigens as Possible Candidates for a New-Generation Recombinant Plague Vaccine

    Science.gov (United States)

    Erova, Tatiana E.; Rosenzweig, Jason A.; Sha, Jian; Suarez, Giovanni; Sierra, Johanna C.; Kirtley, Michelle L.; van Lier, Christina J.; Telepnev, Maxim V.; Motin, Vladimir L.

    2013-01-01

    Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1− strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1− mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1− CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains. PMID:23239803

  10. Evaluation of protective potential of Yersinia pestis outer membrane protein antigens as possible candidates for a new-generation recombinant plague vaccine.

    Science.gov (United States)

    Erova, Tatiana E; Rosenzweig, Jason A; Sha, Jian; Suarez, Giovanni; Sierra, Johanna C; Kirtley, Michelle L; van Lier, Christina J; Telepnev, Maxim V; Motin, Vladimir L; Chopra, Ashok K

    2013-02-01

    Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1(-) strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1(-) mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1(-) CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains.

  11. Kinetics of the immune response to the (F1+V) vaccine in models of bubonic and pneumonic plague.

    Science.gov (United States)

    Williamson, E D; Stagg, A J; Eley, S M; Taylor, R; Green, M; Jones, S M; Titball, R W

    2007-01-22

    Protection against aerosol challenge with > 300 MLD of Yersinia pestis was observed 7 days after a single immunisation of mice with the F1+V vaccine. At day 60, mice were protected against injected challenge (10(7)MLD) in a vaccine dose-related manner. Recall responses to rV in splenocytes ex vivo at day 98 correlated significantly (p<0.001) with the immunising dose-level of V antigen; no memory response or anti-V serum IgG was detected in killed whole cell vaccine (KWCV) recipients. This may explain the susceptibility of KWCV recipients to aerosol challenge and the enhanced protection conferred by the F1+V sub-unit vaccine, particularly since the anti-F1 responses induced by either vaccine were similarly IgG1-polarised.

  12. Modeling of spatio-temporal variation in plague incidence in Madagascar from 1980 to 2007.

    Science.gov (United States)

    Giorgi, Emanuele; Kreppel, Katharina; Diggle, Peter J; Caminade, Cyril; Ratsitorahina, Maherisoa; Rajerison, Minoarisoa; Baylis, Matthew

    2016-11-01

    Plague is an infectious disease caused by the bacterium Yersinia pestis, which, during the fourteenth century, caused the deaths of an estimated 75-200 million people in Europe. Plague epidemics still occur in Africa, Asia and South America. Madagascar is today one of the most endemic countries, reporting nearly one third of the human cases worldwide from 2004 to 2009. The persistence of plague in Madagascar is associated with environmental and climatic conditions. In this paper we present a case study of the spatio-temporal analysis of plague incidence in Madagascar from 1980 to 2007. We study the relationship of plague with temperature and precipitation anomalies, and with elevation. A joint spatio-temporal analysis of the data proves to be computationally intractable. We therefore develop a spatio-temporal log-Gaussian Cox process model, but then carry out marginal temporal and spatial analyses. We also introduce a spatially discrete approximation for Gaussian processes, whose parameters retain a spatially continuous interpretation. We find evidence of a cumulative effect, over time, of temperature anomalies on plague incidence, and of a very high relative risk of plague occurrence for locations above 800 m in elevation. Our approach provides a useful modeling framework to assess the relationship between exposures and plague risk, irrespective of the spatial resolution at which the latter has been recorded. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The Effect of Seasonal Weather Variation on the Dynamics of the Plague Disease

    Directory of Open Access Journals (Sweden)

    Rigobert C. Ngeleja

    2017-01-01

    Full Text Available Plague is a historic disease which is also known to be the most devastating disease that ever occurred in human history, caused by gram-negative bacteria known as Yersinia pestis. The disease is mostly affected by variations of weather conditions as it disturbs the normal behavior of main plague disease transmission agents, namely, human beings, rodents, fleas, and pathogens, in the environment. This in turn changes the way they interact with each other and ultimately leads to a periodic transmission of plague disease. In this paper, we formulate a periodic epidemic model system by incorporating seasonal transmission rate in order to study the effect of seasonal weather variation on the dynamics of plague disease. We compute the basic reproduction number of a proposed model. We then use numerical simulation to illustrate the effect of different weather dependent parameters on the basic reproduction number. We are able to deduce that infection rate, progression rates from primary forms of plague disease to more severe forms of plague disease, and the infectious flea abundance affect, to a large extent, the number of bubonic, septicemic, and pneumonic plague infective agents. We recommend that it is more reasonable to consider these factors that have been shown to have a significant effect on RT for effective control strategies.

  14. Plague Factsheet

    Science.gov (United States)

    ... death rate is over 50%. Geographic Distribution of Plague In the United States, most of the human ... southern Oregon, and far western Nevada. How Is Plague Transmitted? Plague is transmitted from animal to animal ...

  15. Plague dynamics are driven by climate variation.

    Science.gov (United States)

    Stenseth, Nils Chr; Samia, Noelle I; Viljugrein, Hildegunn; Kausrud, Kyrre Linné; Begon, Mike; Davis, Stephen; Leirs, Herwig; Dubyanskiy, V M; Esper, Jan; Ageyev, Vladimir S; Klassovskiy, Nikolay L; Pole, Sergey B; Chan, Kung-Sik

    2006-08-29

    The bacterium Yersinia pestis causes bubonic plague. In Central Asia, where human plague is still reported regularly, the bacterium is common in natural populations of great gerbils. By using field data from 1949-1995 and previously undescribed statistical techniques, we show that Y. pestis prevalence in gerbils increases with warmer springs and wetter summers: A 1 degrees C increase in spring is predicted to lead to a >50% increase in prevalence. Climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague pandemic arose in the same region, and they are expected to continue or become more favorable as a result of climate change. Threats of outbreaks may thus be increasing where humans live in close contact with rodents and fleas (or other wildlife) harboring endemic plague.

  16. Current epidemiology of human plague in Madagascar.

    Science.gov (United States)

    Chanteau, S; Ratsitorahina, M; Rahalison, L; Rasoamanana, B; Chan, F; Boisier, P; Rabeson, D; Roux, J

    2000-01-01

    From 1996 to 1998, 5,965 patients with suspected plague were identified in 38 districts of Madagascar (40% of the total population are exposed). Using standard bacteriology, 917 of them were confirmed or presumptive (C + P) cases. However, more than 2,000 plague cases could be estimated using F1 antigen assay. Two out of the 711 Yersinia pestis isolates tested were resistant to chloramphenicol and to ampicillin (both isolates found in the harbour of Mahajanga). Urban plague (Mahajanga harbour and Antananarivo city) accounted for 37.4% of the C + P cases. Bubonic plague represented 97.2% of the cases, and the lethality rate was still high (20%). In comparing the exposed population, plague was more prevalent in males (M:F sex ratio 1.3:1) and patients under 20 years (2.7% babies under two years). Buboes were mainly localised in the inguinal/femoral regions (55.8%). The epidemiological risk factors are discussed.

  17. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  18. Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

    Science.gov (United States)

    Tiner, Bethany L.; Kirtley, Michelle L.; Erova, Tatiana E.; Popov, Vsevolod L.; Baze, Wallace B.; van Lier, Christina J.; Ponnusamy, Duraisamy; Andersson, Jourdan A.; Motin, Vladimir L.; Chauhan, Sadhana

    2015-01-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  19. Spatial analysis of plague in California: niche modeling predictions of the current distribution and potential response to climate change

    Science.gov (United States)

    Holt, Ashley C; Salkeld, Daniel J; Fritz, Curtis L; Tucker, James R; Gong, Peng

    2009-01-01

    Background Plague, caused by the bacterium Yersinia pestis, is a public and wildlife health concern in California and the western United States. This study explores the spatial characteristics of positive plague samples in California and tests Maxent, a machine-learning method that can be used to develop niche-based models from presence-only data, for mapping the potential distribution of plague foci. Maxent models were constructed using geocoded seroprevalence data from surveillance of California ground squirrels (Spermophilus beecheyi) as case points and Worldclim bioclimatic data as predictor variables, and compared and validated using area under the receiver operating curve (AUC) statistics. Additionally, model results were compared to locations of positive and negative coyote (Canis latrans) samples, in order to determine the correlation between Maxent model predictions and areas of plague risk as determined via wild carnivore surveillance. Results Models of plague activity in California ground squirrels, based on recent climate conditions, accurately identified case locations (AUC of 0.913 to 0.948) and were significantly correlated with coyote samples. The final models were used to identify potential plague risk areas based on an ensemble of six future climate scenarios. These models suggest that by 2050, climate conditions may reduce plague risk in the southern parts of California and increase risk along the northern coast and Sierras. Conclusion Because different modeling approaches can yield substantially different results, care should be taken when interpreting future model predictions. Nonetheless, niche modeling can be a useful tool for exploring and mapping the potential response of plague activity to climate change. The final models in this study were used to identify potential plague risk areas based on an ensemble of six future climate scenarios, which can help public managers decide where to allocate surveillance resources. In addition, Maxent

  20. Spatial analysis of plague in California: niche modeling predictions of the current distribution and potential response to climate change

    Directory of Open Access Journals (Sweden)

    Tucker James R

    2009-06-01

    Full Text Available Abstract Background Plague, caused by the bacterium Yersinia pestis, is a public and wildlife health concern in California and the western United States. This study explores the spatial characteristics of positive plague samples in California and tests Maxent, a machine-learning method that can be used to develop niche-based models from presence-only data, for mapping the potential distribution of plague foci. Maxent models were constructed using geocoded seroprevalence data from surveillance of California ground squirrels (Spermophilus beecheyi as case points and Worldclim bioclimatic data as predictor variables, and compared and validated using area under the receiver operating curve (AUC statistics. Additionally, model results were compared to locations of positive and negative coyote (Canis latrans samples, in order to determine the correlation between Maxent model predictions and areas of plague risk as determined via wild carnivore surveillance. Results Models of plague activity in California ground squirrels, based on recent climate conditions, accurately identified case locations (AUC of 0.913 to 0.948 and were significantly correlated with coyote samples. The final models were used to identify potential plague risk areas based on an ensemble of six future climate scenarios. These models suggest that by 2050, climate conditions may reduce plague risk in the southern parts of California and increase risk along the northern coast and Sierras. Conclusion Because different modeling approaches can yield substantially different results, care should be taken when interpreting future model predictions. Nonetheless, niche modeling can be a useful tool for exploring and mapping the potential response of plague activity to climate change. The final models in this study were used to identify potential plague risk areas based on an ensemble of six future climate scenarios, which can help public managers decide where to allocate surveillance resources

  1. Modeling the epidemiological history of plague in Central Asia: Palaeoclimatic forcing on a disease system over the past millennium

    Science.gov (United States)

    2010-01-01

    Background Human cases of plague (Yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. The epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. Earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans. Results We find that high-resolution palaeoclimatic indices correlate with plague prevalence and population density in a major plague host species, the great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on these data predict independent data on human plague cases in early 20th-century Kazakhstan from 1904-1948, suggesting a consistent impact of climate on large-scale wildlife reservoir dynamics influencing human epidemics. Extending the models further back in time, we also find correspondence between their predictions and qualitative records of plague epidemics over the past 1500 years. Conclusions Central Asian climate fluctuations appear to have had significant influences on regional human plague frequency in the first part of the 20th century, and probably over the past 1500 years. This first attempt at ecoepidemiological reconstruction of historical disease activity may shed some light on how long-term plague epidemiology interacts with human activity. As plague activity in Central Asia seems to have followed climate fluctuations over the past centuries, we may expect global warming to have an impact upon future plague epidemiology, probably sustaining or increasing plague activity in the region, at least in the rodent reservoirs, in the coming decades. See commentary: http://www.biomedcentral.com/1741-7007/8/108 PMID:20799946

  2. Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis.

    Science.gov (United States)

    Mitchell, Anthony; Tam, Christina; Elli, Derek; Charlton, Thomas; Osei-Owusu, Patrick; Fazlollahi, Farbod; Faull, Kym F; Schneewind, Olaf

    2017-05-16

    Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that Yersinia pestis LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys273 and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys273Ala in lcrV Moreover, the lcrVC273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala substitution. Furthermore, macrophages infected by the lcrVC273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis, resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis ΔgshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.IMPORTANCEYersinia pestis, the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of Y. pestis in mouse and rat models for bubonic

  3. Residence-linked human plague in New Mexico: a habitat-suitability model.

    Science.gov (United States)

    Eisen, Rebecca J; Reynolds, Pamela J; Ettestad, Paul; Brown, Ted; Enscore, Russell E; Biggerstaff, Brad J; Cheek, James; Bueno, Rudy; Targhetta, Joseph; Montenieri, John A; Gage, Kenneth L

    2007-07-01

    Yersinia pestis, the causative agent of plague, has been detected in fleas and mammals throughout the western United States. This highly virulent infection is rare in humans, surveillance of the disease is expensive, and it often was assumed that risk of exposure to Y. pestis is high in most of the western United States. For these reasons, some local health departments in these plague-affected regions have hesitated to undertake surveillance and other prevention activities. To aid in targeting limited public health resources, we created a fine-resolution human plague risk map for New Mexico, the state reporting more than half the human cases in the United States. Our GIS-based model included three landscape features-a nonlinear relationship with elevation, distance to water, and distance to the ecotone between Rocky Mountain/Great Basin open and closed coniferous woodlands-and yielded an overall accuracy of approximately 80%. The model classified 17.25% of the state as posing significant risk of exposure to humans on privately or tribally owned land, which suggests that resource requirements for regular surveillance and control of plague could be effectively focused on < 20% of the state.

  4. Plague Prevention

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Plague Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics ...

  5. Plague Symptoms

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Plague Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics ...

  6. Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis

    Directory of Open Access Journals (Sweden)

    Anthony Mitchell

    2017-05-01

    Full Text Available Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that Yersinia pestis LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys273 and that this modification promotes association with host ribosomal protein S3 (RPS3, moderates Y. pestis type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys273Ala in lcrV. Moreover, the lcrVC273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala substitution. Furthermore, macrophages infected by the lcrVC273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis, resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis ΔgshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.

  7. [Update on plague in Madagascar].

    Science.gov (United States)

    Chanteau, S; Rahalison, L; Duplantier, J M; Rasoamanana, B; Ratsitorahina, M; Dromigny, J A; Laventure, S; Duchemin, J B; Boisier, P; Rabeson, D; Roux, J

    1998-01-01

    After a thirty year period of successful control, bubonic plague showed the first signs of return in Madagascar where a fatal outbreak occurred in Antananarivo in 1978. A second outbreak was observed in Mahajanga in 1991 after more than a half century. In 1997, 459 confirmed or presumptive cases were reported, as compared to 150 to 250 cases during the last years. However the actual extent of this recrudescence must be placed in the perspective of a more efficient control program that has led to better reporting of suspected cases and availability of more accurate diagnostic techniques. Recent research has led to the development of highly effective immunological diagnostic tools (detection of antibodies and F1 antigen) allowing not only better surveillance of the disease in man and animals but also renewed study of the epidemiological cycle in the current environment. In this regard the capacity of several endemic fleas as vectors and the role of the rat Rattus norvegicus and the musk shrew Suncus murinus are currently under investigation. Genetic study of strains collected from 1936 to 1996 has demonstrated the appearance of 3 new ribotypes of Yersinia pestis since 1982 in the zones of strongest plague activity in Madagascar. A strain showing multiresistance to standard therapeutic antibiotic agents was isolated in 1995. Bubonic plaque is a priority health problem in Madagascar but remains a major concern for the rest of the world.

  8. [The Justinian plague (part one)].

    Science.gov (United States)

    Sabbatani, Sergio; Manfredi, Roberto; Fiorino, Sirio

    2012-06-01

    In their medical-historical review, the authors assess the evolution of bubonic plague epidemics: after breaking out in the Egyptian port of Pelusium in October 541 AD, the epidemics hit several regions in the Mediterranean basin in a succession of waves. The so-called Justinian plague took its name from the Byzantine emperor of the period, and seriously conditioned the expansionary aims of the Eastern Roman empire towards Italy (which was occupied by Goths), and Northern Africa (where the Vandals had settled), during the first decades of its spread. In the Eastern Empire the plague played a considerable role in reducing the tensions between Persians and Byzantines, especially on the Syrian and Anatolian fronts. It had a major demographic impact, reducing the possibility of recruitment to the Roman legions and leading to a significant drop in tax revenues, which were essential to sustain the state and its military machine. Finally, the plague also took its toll on economic resources (especially agriculture), indirectly leading to a vicious inflationary circle. In the space of over two centuries, plague epidemics paralyzed most trade and commercial exchanges. Furthermore, the Justinian plague, halting the consolidation of the influence of the Eastern Roman empire over some Western regions (including Italy and Northern Africa, which were ruled by Barbarians), supported the development and rise of a number of Roman-Barbarian kingdoms. It may therefore be suggested that the Justinian plague occurred at a very critical historical moment, which represents the real watershed between the Ancient World and the upcoming Middle Ages.

  9. [Yersinia pestis and plague - an update].

    Science.gov (United States)

    Stock, Ingo

    2014-12-01

    The plague of man is a severe, systemic bacterial infectious disease. Without antibacterial therapy, the disease is associated with a high case fatality rate, ranging from 40% (bubonic plague) to nearly 100% (septicemic and pneumonic plague). The disease is caused by Yersinia pestis, a non-motile, gram-negative, facultative anaerobic bacterium belonging to the family of Enterobacteriaceae. In nature, Y. pestis has been found in several rodent species and some other small animals such as shrews. Within its reservoir host, Y. pestis circulates via flea bites. Transmission of Y. pestis to humans occurs by the bite of rat fleas, other flea vectors or by non vectorial routes, e. g., handling infected animals or consumption of contaminated food. Human-to-human transmission of the pathogen occurs primarily through aerosol droplets. Compared to the days when plague was a pandemic scourge, the disease is now relatively rare and limited to some rural areas of Africa. During the last ten years, however, plague outbreaks have been registered repea- tedly in some African regions. For treatment of plague, streptomycin is still considered the drug of choice. Chloramphenicol, doxycycline, gentamicin and ciprofloxacin are also promising drugs. Recombinant vaccines against plague are in clinical development.

  10. Prediction of Frost Risks and Plagues using WRF model: a Port Wine region case study

    Science.gov (United States)

    Rodrigues, M. A.; Rocha, A.; Monteiro, A.; Quénol, H.; de Freitas, J. R.

    2012-04-01

    In viticulture where the quality of the wine, the selection of the grapevines or even the characteristics of the farming soil, also depending from local soil features like topography, proximity of a river or water body, will act locally on the weather. Frosts are of significant concern to growers of many cultures crops such as winegrapes. Because of their high latitude and some altitude, the vineyards of the Demarcated Douro Region (DDR) are subjected to the frost, which cause serious damages. But the hazards of vineyard don't confine to the incidents of the fortuitous and meteorological character. The illnesses and plagues affect frequently the vineyards of Demarcated Douro Region due, namely to the weather, to the high power of the regional stocks, to the dense vegetation badly drained and favourable to the setting of numberless fungi, viruses and/or poisonous insects. In the case of DDR it is worth noticing the meteorological conditions due to the weather characteristics. Although there are several illnesses and plagues the most important enemies for the vine in the DDR are the mildew, oidium, grey rottenness, grape moth,. . . , if the climatic conditions favour their appearance and development. For this study, we selected some months for different periods, at the 16 weather stations of the Region of Douro. We use the Weather Research and Forecast Model (WRF) to study and possibly predict the occurrence of risk and plagues (mildew) episodes. The model is first validated with the meteorological data obtained at the weather stations. The knowledge of frost and plagues occurrence allows one to decrease its risks not only by selecting the cultural species and varieties but also the places of growth and the planting and sowing dates.

  11. [Clinical epidemiology of plague in Madagascar (current data)].

    Science.gov (United States)

    Blanchy, S; Ranaivoson, G; Rakotojanabelo, A

    1993-01-01

    After a recall of the epidemiological cycle of plague, the authors describe the course of this disease from 1989 to 1992. Out of 2676 pathological samples suspected of plague, 2105 biological examinations were carried out. 312 cases were confirmed and 335 considered as probable. 93% of those positive cases come from the plague triangle located in the Central Highlands and delimited by Ambatondrazaka, Miarinarivo and Fianarantsoa and they occur during the rainy season (November to March). However, an outbreak of urban epidemics is possible on the coast during the cold season. The most frequent clinical form had been bubonic plague (90%). Plague did not much concern young children and men are affected more often than women. Clinically, toxi-infectious syndrome, lymph node reaction and hemoptoïc spits can be noted. The 1989-1992 results are compared with those of the two previous studies.

  12. Plague: Frequently Asked Questions

    Science.gov (United States)

    ... a vaccine available to prevent plague? What is plague? Plague is an infectious disease that affects rodents, ... United States. How do people become infected with plague? People most commonly acquire plague when they are ...

  13. The biblical plague of the Philistines now has a name, tularemia

    OpenAIRE

    Trevisanato, Siro Igino

    2007-01-01

    Abstract An epidemic thought to have been the first instance of bubonic plague in the Mediterranean reveals to have been an episode of tularemia. The deadly epidemic took place in the aftermath of the removal of a wooden box from an isolated Hebrew sanctuary. Death, tumors, and rodents thereafter plagued Philistine country. Unlike earlier explanations proposed, tularemia caused by Francisella tularensis exhaustively explains the outbreak. Tularemia fits all the requirements indicated in th...

  14. [The plague in Madagascar: epidemiologic data from 1989 to 1995 and the national control program].

    Science.gov (United States)

    Champetier de Ribes, G; Rasoamanana, B; Randriambelosoa, J; Rakoto, L J; Rabescn, D; Chanteau, S

    1997-01-01

    After briefly reviewing the history and epidemiological cycle of the plague in Madagascar, we report a detailed analysis of 5,927 suspected cases of plague observed from 1989 to 1995 (average of 846 cases per year). Of those, 1,337 individuals (average of 191 cases per year) were confirmed (by isolation of Yersinia pestis) or indicated to be probable for plague (by positive smears). Since 1994, we observed an increasing number of confirmed and probable cases (252 cases in 1995). Most of the cases occurred between October and April in the central highlands, inside a geographical triangle limited by Alaotra lake, Itasy lake and the city of Fianarantsoa. Two exceptional epidemics occurred in the harbor of Majunga in 1991 and 1995. The bubonic plague was the most frequent clinical from (91.3%), with primarily an inguinal localization (67.8%). The mean case fatality rate was 19% of the confirmed or probable cases (14.8% for the bubonic form and 57.1% for the pneumonic form). The bubonic plague was significantly more frequent between the ages of 5 and 14 years, as compared to the general population, while the pneumonic plague was more frequent over 15 years of age. Males were more effected by the bubonic form, as the sex ratio (m:f) was 1.3. The national control program for plague is being strengthened to improve 1) the patient's early diagnosis and care system; 2) the measures for the prevention of epidemics; 3) the epidemiological surveillance; and 4) the studies on the biology of the plague vectors, rodents and fleas, and the agent, bacilli, in Madagascar.

  15. Improvement of Disease Prediction and Modeling through the Use of Meteorological Ensembles: Human Plague in Uganda

    Science.gov (United States)

    Moore, Sean M.; Monaghan, Andrew; Griffith, Kevin S.; Apangu, Titus; Mead, Paul S.; Eisen, Rebecca J.

    2012-01-01

    Climate and weather influence the occurrence, distribution, and incidence of infectious diseases, particularly those caused by vector-borne or zoonotic pathogens. Thus, models based on meteorological data have helped predict when and where human cases are most likely to occur. Such knowledge aids in targeting limited prevention and control resources and may ultimately reduce the burden of diseases. Paradoxically, localities where such models could yield the greatest benefits, such as tropical regions where morbidity and mortality caused by vector-borne diseases is greatest, often lack high-quality in situ local meteorological data. Satellite- and model-based gridded climate datasets can be used to approximate local meteorological conditions in data-sparse regions, however their accuracy varies. Here we investigate how the selection of a particular dataset can influence the outcomes of disease forecasting models. Our model system focuses on plague (Yersinia pestis infection) in the West Nile region of Uganda. The majority of recent human cases have been reported from East Africa and Madagascar, where meteorological observations are sparse and topography yields complex weather patterns. Using an ensemble of meteorological datasets and model-averaging techniques we find that the number of suspected cases in the West Nile region was negatively associated with dry season rainfall (December-February) and positively with rainfall prior to the plague season. We demonstrate that ensembles of available meteorological datasets can be used to quantify climatic uncertainty and minimize its impacts on infectious disease models. These methods are particularly valuable in regions with sparse observational networks and high morbidity and mortality from vector-borne diseases. PMID:23024750

  16. Improvement of disease prediction and modeling through the use of meteorological ensembles: human plague in Uganda.

    Directory of Open Access Journals (Sweden)

    Sean M Moore

    Full Text Available Climate and weather influence the occurrence, distribution, and incidence of infectious diseases, particularly those caused by vector-borne or zoonotic pathogens. Thus, models based on meteorological data have helped predict when and where human cases are most likely to occur. Such knowledge aids in targeting limited prevention and control resources and may ultimately reduce the burden of diseases. Paradoxically, localities where such models could yield the greatest benefits, such as tropical regions where morbidity and mortality caused by vector-borne diseases is greatest, often lack high-quality in situ local meteorological data. Satellite- and model-based gridded climate datasets can be used to approximate local meteorological conditions in data-sparse regions, however their accuracy varies. Here we investigate how the selection of a particular dataset can influence the outcomes of disease forecasting models. Our model system focuses on plague (Yersinia pestis infection in the West Nile region of Uganda. The majority of recent human cases have been reported from East Africa and Madagascar, where meteorological observations are sparse and topography yields complex weather patterns. Using an ensemble of meteorological datasets and model-averaging techniques we find that the number of suspected cases in the West Nile region was negatively associated with dry season rainfall (December-February and positively with rainfall prior to the plague season. We demonstrate that ensembles of available meteorological datasets can be used to quantify climatic uncertainty and minimize its impacts on infectious disease models. These methods are particularly valuable in regions with sparse observational networks and high morbidity and mortality from vector-borne diseases.

  17. Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Guang Tian

    Full Text Available In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270 and SV2 (200 µg F1 and 100 µg rV270 subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

  18. [The epidemiology and etiology research of Tibetan sheep plague in Qinghai plateau].

    Science.gov (United States)

    Wei, Baiqing; Xiong, Haoming; Yang, Xiaoyan; Yang, Yonghai; Qi, Meiying; Jin, Juan; Xin, Youquan; Li, Xiang; Yang, Hanqing; Han, Xiumin; Dai, Ruixia

    2015-03-01

    To identify the epidemiology and etiology characteristics of Tibetan sheep plague in Qinghai plateau. The background materials of Qinghai Tibetan sheep plague found during 1975 to 2009 were summarized, the regional, time and interpersonal distribution, infection routes, ecological factors for the spread were used to analyze; followed by choosing 14 Yersinia pestis strains isolated from such sheep for biochemical test, toxicity test, virulence factors identification, plasmid analysis, and DFR genotype. From 1975 to 2009, 14 Yersinia pestis strains were isolated from Tibetan sheep in Qinghai province. Tibetan sheep, as the infection source, had caused 10 cases of human plague, 25 plague patients, and 13 cases of death. All of the initial cases were infected due to eating Tibetan sheep died of plague; followed by cases due to contact of plague patients, while all the initial cases were bubonic plague. Cases of bubonic plague developed into secondary pneumonic plague and septicemia plague were most popular and with high mortality. Most of the Tibetan sheep plague and human plague occurred in Gannan ecological zone in southern Gansu province, which was closely related to its unique ecological and geographical landscape. Tibetan sheep plague coincided with human plague caused by Tibetan sheep, especially noteworthy was that November (a time for marmots to start their dormancy) witnesses the number of Yersinia pestis strains isolated from Tibetan sheep and human plague cases caused by Tibetan sheep. This constituted the underlying cause that the epidemic time of Tibetan sheep plague lags obviously behind that of the Marmot plague. It was confirmed in the study that all the 14 strains were of Qinghai-Tibet Plateau ecotype, with virulence factors evaluation and toxicity test demonstrating strains as velogenic. As found in the (Different Region) DFR genotyping, the strains isolated from Yushu county and Zhiduo county were genomovar 5, the two strain isolated from Nangqian

  19. Plague Maps and Statistics

    Science.gov (United States)

    ... and Statistics Recommend on Facebook Tweet Share Compartir Plague in the United States Plague was first introduced ... per year in the United States: 1900-2012. Plague Worldwide Plague epidemics have occurred in Africa, Asia, ...

  20. Plague in China 2014-All sporadic case report of pneumonic plague.

    Science.gov (United States)

    Li, Yun-Fang; Li, De-Biao; Shao, Hong-Sheng; Li, Hong-Jun; Han, Yue-Dong

    2016-02-19

    Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post-exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist.

  1. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The

  2. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  3. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  4. [The spread of the plague: A sciento-historiographic review].

    Science.gov (United States)

    Cuadrada, Coral

    2015-01-01

    There is still uncertainty about the diagnosis and nature of the plague; some scholars have been forced to abandon certainties and be filled with doubts: from believing that the mediaeval Black Plague was, in reality, the bubonic plague (although with unusual characteristics) to stating that there is very little evidence to support a retro-diagnosis. This article looks at this in depth, not only reviewing the historiography but also giving new interpretations which question previous hypotheses through research on images of the time, comparing them to the most recent investigative data. Two primary sources are analysed: Renaissance treaties written by four Italian doctors: Michele Savonarola, Marsilio Ficino, Leonardo Fioravanti and Gioseffo Daciano; and iconography: an illustrated manuscript of the Decameron by Giovanni Boccaccio and a Hebrew Haggadah from the XIVth century. The results are compared to the most recent research on DNA and in micropaleontology.

  5. Ecologic Features of Plague Outbreak Areas, Democratic Republic of the Congo, 2004–2014

    Science.gov (United States)

    Shako, Jean-Christophe; Gaudart, Jean; Sudre, Bertrand; Ilunga, Benoit Kebela; Shamamba, Stomy Karhemere Bi; Diatta, Georges; Davoust, Bernard; Tamfum, Jean-Jacques Muyembe; Piarroux, Renaud; Piarroux, Martine

    2018-01-01

    During 2004–2014, the Democratic Republic of the Congo (DRC) declared 54% of plague cases worldwide. Using national data, we characterized the epidemiology of human plague in DRC for this period. All 4,630 suspected human plague cases and 349 deaths recorded in DRC came from Orientale Province. Pneumonic plague cases (8.8% of total) occurred during 2 major outbreaks in mining camps in the equatorial forest, and some limited outbreaks occurred in the Ituri highlands. Epidemics originated in 5 health zones clustered in Ituri, where sporadic bubonic cases were recorded throughout every year. Classification and regression tree characterized this cluster by the dominance of ecosystem 40 (mountain tropical climate). In conclusion, a small, stable, endemic focus of plague in the highlands of the Ituri tropical region persisted, acting as a source of outbreaks in DRC. PMID:29350136

  6. Earthquakes and plague during Byzantine times: can lessons from the past improve epidemic preparedness.

    Science.gov (United States)

    Tsiamis, Costas; Poulakou-Rebelakou, Effie; Marketos, Spyros

    2013-01-01

    Natural disasters have always been followed by a fear of infectious diseases. This raised historical debate about one of the most feared scenarios: the outbreak of bubonic plague caused by Yersinia pestis. One such event was recorded in the Indian state Maharashtra in 1994 after an earthquake. In multidisciplinary historical approach to the evolution of plague, many experts ignore the possibility of natural foci and their activation. This article presents historical records from the Byzantine Empire about outbreaks of the Plague of Justinian occurring months or even up to a year after high-magnitude earthquakes. Historical records of plague outbreaks can be used to document existence of natural foci all over the world. Knowledge of these historical records and the contemporary examples of plague support the assumption that, in terms of organising humanitarian aid, poor monitoring of natural foci could lead to unpredictable epidemiological consequences after high-magnitude earthquakes.

  7. Modeling the Impact of White-Plague Coral Disease in Climate Change Scenarios.

    Science.gov (United States)

    Zvuloni, Assaf; Artzy-Randrup, Yael; Katriel, Guy; Loya, Yossi; Stone, Lewi

    2015-06-01

    Coral reefs are in global decline, with coral diseases increasing both in prevalence and in space, a situation that is expected only to worsen as future thermal stressors increase. Through intense surveillance, we have collected a unique and highly resolved dataset from the coral reef of Eilat (Israel, Red Sea), that documents the spatiotemporal dynamics of a White Plague Disease (WPD) outbreak over the course of a full season. Based on modern statistical methodologies, we develop a novel spatial epidemiological model that uses a maximum-likelihood procedure to fit the data and assess the transmission pattern of WPD. We link the model to sea surface temperature (SST) and test the possible effect of increasing temperatures on disease dynamics. Our results reveal that the likelihood of a susceptible coral to become infected is governed both by SST and by its spatial location relative to nearby infected corals. The model shows that the magnitude of WPD epidemics strongly depends on demographic circumstances; under one extreme, when recruitment is free-space regulated and coral density remains relatively constant, even an increase of only 0.5°C in SST can cause epidemics to double in magnitude. In reality, however, the spatial nature of transmission can effectively protect the community, restricting the magnitude of annual epidemics. This is because the probability of susceptible corals to become infected is negatively associated with coral density. Based on our findings, we expect that infectious diseases having a significant spatial component, such as Red-Sea WPD, will never lead to a complete destruction of the coral community under increased thermal stress. However, this also implies that signs of recovery of local coral communities may be misleading; indicative more of spatial dynamics than true rehabilitation of these communities. In contrast to earlier generic models, our approach captures dynamics of WPD both in space and time, accounting for the highly

  8. Modeling the Impact of White-Plague Coral Disease in Climate Change Scenarios.

    Directory of Open Access Journals (Sweden)

    Assaf Zvuloni

    2015-06-01

    Full Text Available Coral reefs are in global decline, with coral diseases increasing both in prevalence and in space, a situation that is expected only to worsen as future thermal stressors increase. Through intense surveillance, we have collected a unique and highly resolved dataset from the coral reef of Eilat (Israel, Red Sea, that documents the spatiotemporal dynamics of a White Plague Disease (WPD outbreak over the course of a full season. Based on modern statistical methodologies, we develop a novel spatial epidemiological model that uses a maximum-likelihood procedure to fit the data and assess the transmission pattern of WPD. We link the model to sea surface temperature (SST and test the possible effect of increasing temperatures on disease dynamics. Our results reveal that the likelihood of a susceptible coral to become infected is governed both by SST and by its spatial location relative to nearby infected corals. The model shows that the magnitude of WPD epidemics strongly depends on demographic circumstances; under one extreme, when recruitment is free-space regulated and coral density remains relatively constant, even an increase of only 0.5°C in SST can cause epidemics to double in magnitude. In reality, however, the spatial nature of transmission can effectively protect the community, restricting the magnitude of annual epidemics. This is because the probability of susceptible corals to become infected is negatively associated with coral density. Based on our findings, we expect that infectious diseases having a significant spatial component, such as Red-Sea WPD, will never lead to a complete destruction of the coral community under increased thermal stress. However, this also implies that signs of recovery of local coral communities may be misleading; indicative more of spatial dynamics than true rehabilitation of these communities. In contrast to earlier generic models, our approach captures dynamics of WPD both in space and time, accounting for

  9. [The arrival of the plague in São Paulo in 1899].

    Science.gov (United States)

    do Nascimento, Dilene Raimundo

    2011-01-01

    In October 1899, the bubonic plague arrived in Brazil through the port of Santos. A city of intensive port activity, Santos was the gateway for a plague epidemic that devastated several cities in Brazil in the early 20th century and prompted joint action by several states to fight it. More importantly, given the difficulties and delays in importing anti-plague serum from Europe, it led to the creation of the Butantan Institute in Sao Paulo (in 1899) and the Municipal Serotherapeutic Institute in Rio de Janeiro (in 1900), which developed and standardized anti-plague serum and vaccines according to the particular conditions of the country. Until then, public health efforts had been isolated and had not reached the whole country. Oswaldo Cruz, newly arrived after three years of specialization at the Pasteur Institute in Paris, worked with scientists Adolfo Lutz and Vital Brazil on identifying the plague in Santos. This article analyzes the arrival of the bubonic plague epidemic in the state of Sao Paulo and the public health measures taken to combat the disease and provide patient care in the early part of the 20th century. The primary sources for this analysis were the São Paulo newspapers, especially O Estado de Sao Paulo, and reports from the Ministry of Justice and the President of the State of Sao Paulo.

  10. Oral vaccination against plague using Yersinia pseudotuberculosis.

    Science.gov (United States)

    Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth

    2017-04-01

    Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Modeling the ecologic niche of plague in sylvan and domestic animal hosts to delineate sources of human exposure in the western United States

    Directory of Open Access Journals (Sweden)

    Michael Walsh

    2015-12-01

    Full Text Available Plague has been established in the western United States (US since 1900 following the West Coast introduction of commensal rodents infected with Yersinia pestis via early industrial shipping. Over the last century, plague ecology has transitioned through cycles of widespread human transmission, urban domestic transmission among commensal rodents, and ultimately settled into the predominantly sylvan foci that remain today where it is maintained alternatively by enzootic and epizootic transmission. While zoonotic transmission to humans is much less common in modern times, significant plague risk remains in parts of the western US. Moreover, risk to some threatened species that are part of the epizootic cycle can be quite substantive. This investigation attempted to predict the risk of plague across the western US by modeling the ecologic niche of plague in sylvan and domestic animals identified between 2000 and 2015. A Maxent machine learning algorithm was used to predict this niche based on climate, altitude, land cover, and the presence of an important enzootic species, Peromyscus maniculatus. This model demonstrated good predictive ability (AUC = 86% and identified areas of high risk in central Colorado, north-central New Mexico, and southwestern and northeastern California. The presence of P. maniculatus, altitude, precipitation during the driest and wettest quarters, and distance to artificial surfaces, all contributed substantively to maximizing the gain function. These findings add to the known landscape epidemiology and infection ecology of plague in the western US and may suggest locations of particular risk to be targeted for wild and domestic animal intervention.

  12. Climate-driven introduction of the Black Death and successive plague reintroductions into Europe

    Czech Academy of Sciences Publication Activity Database

    Schmid, B. V.; Büntgen, Ulf; Easterday, W. R.; Ginzler, Ch.; Walloe, L.; Bramanti, B.; Stenseth, N. C.

    2015-01-01

    Roč. 112, č. 10 (2015), s. 3020-3025 ISSN 0027-8424 Institutional support: RVO:67179843 Keywords : yersinia-pestis * xenopsylla-cheopis * bubonic plague * central-asia * synchrony * dynamics * transmission * temperature * populations * thresholds * Yersinia pestis * medieval epidemiology * climate-driven disease dynamics Subject RIV: EH - Ecology, Behaviour Impact factor: 9.423, year: 2015 http://www.pnas.org/content/112/10/3020.full.pdf

  13. Proteolytic processing of the Yersinia pestis YapG autotransporter by the omptin protease Pla and the contribution of YapG to murine plague pathogenesis

    Science.gov (United States)

    Lane, M. Chelsea; Lenz, Jonathan D.

    2013-01-01

    Autotransporter protein secretion represents one of the simplest forms of secretion across Gram-negative bacterial membranes. Once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. Autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. To better understand the role of autotransporters in disease, our research focused on the autotransporters of Yersinia pestis, the aetiological agent of plague. Y. pestis strain CO92 has nine functional conventional autotransporters, referred to as Yaps for Yersinia autotransporter proteins. Three Yaps have been directly implicated in virulence using established mouse models of plague infection (YapE, YapJ and YapK). Whilst previous studies from our laboratory have shown that most of the CO92 Yaps are cell associated, YapE and YapG are processed and released by the omptin protease Pla. In this study, we identified the Pla cleavage sites in YapG that result in many released forms of YapG in Y. pestis, but not in the evolutionarily related gastrointestinal pathogen, Yersinia pseudotuberculosis, which lacks Pla. Furthermore, we showed that YapG does not contribute to Y. pestis virulence in established mouse models of bubonic and pneumonic infection. As Y. pestis has a complex life cycle involving a wide range of mammalian hosts and a flea vector for transmission, it remains to be elucidated whether YapG has a measurable role in any other stage of plague disease. PMID:23657527

  14. Efficacy of primate humoral passive transfer in a murine model of pneumonic plague is mouse strain-dependent.

    Science.gov (United States)

    Graham, V A; Hatch, G J; Bewley, K R; Steeds, K; Lansley, A; Bate, S R; Funnell, S G P

    2014-01-01

    New vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the US Federal Drug Administration's "Animal Rule." This allows licensure of drugs and vaccines using protection data generated in animal models. A new acellular plague vaccine composed of two separate recombinant proteins (rF1 and rV) has been developed and assessed for immunogenicity in humans. Using serum obtained from human volunteers immunised with various doses of this vaccine and from immunised cynomolgus macaques, we assessed the pharmacokinetic properties of human and cynomolgus macaque IgG in BALB/c and the NIH Swiss derived Hsd:NIHS mice, respectively. Using human and cynomolgus macaque serum with known ELISA antibody titres against both vaccine components, we have shown that passive immunisation of human and nonhuman primate serum provides a reproducible delay in median time to death in mice exposed to a lethal aerosol of plague. In addition, we have shown that Hsd:NIHS mice are a better model for humoral passive transfer studies than BALB/c mice.

  15. Deletion of the Braun lipoprotein-encoding gene and altering the function of lipopolysaccharide attenuate the plague bacterium.

    Science.gov (United States)

    Sha, Jian; Kirtley, Michelle L; van Lier, Christina J; Wang, Shaofei; Erova, Tatiana E; Kozlova, Elena V; Cao, Anthony; Cong, Yingzi; Fitts, Eric C; Rosenzweig, Jason A; Chopra, Ashok K

    2013-03-01

    Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a Δlpp ΔmsbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ΔmsbB single mutant was minimally attenuated, the Δlpp single mutant and the Δlpp ΔmsbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the Δlpp ΔmsbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the Δlpp ΔmsbB double mutant, but not the Δlpp or ΔmsbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the Δlpp ΔmsbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the Δlpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the Δlpp ΔmsbB double mutant could provide a new live-attenuated background

  16. Plague Diagnosis and Treatment

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Plague Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics ...

  17. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

    Science.gov (United States)

    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Seroepidemiology of human plague in the Madagascar highlands.

    Science.gov (United States)

    Ratsitorahina, M; Rabarijaona, L; Chanteau, S; Boisier, P

    2000-02-01

    We conducted a seroepidemiological survey of human plague in the general population using random sampling in the area of Ambositra, the main focus of plague in the central highlands of Madagascar (520 confirmed and presumptive cases notified during the past 10 years). Sera were tested using an ELISA IgG F1 assay. Considering the internal validity of the assay and the sampling method, the overall corrected prevalence of F1 antibodies was 0.6% (95% CI: 0.2%-1.8%). Being nearly 0 up to the age of 40, the corrected prevalence increased markedly after 45 years to 6.2%. Six of 20 individuals who declared to have been treated for clinical suspicion of bubonic plague in the past had F1 antibodies. The seroprevalence did not differ according to gender except in individuals > 60, where antibodies were significantly more frequent in males. This study suggests that the number of clinically suspected cases of plague provided by the surveillance network was plausible, despite some true cases being missed and a significant number of false positives. We also confirm that Yersinia pestis infections may occur without marked clinical manifestations and patients may recover without treatment, in accordance with old observations of pestis minor.

  19. Investigation of and Response to 2 Plague Cases, Yosemite National Park, California, USA, 2015

    Science.gov (United States)

    Danforth, Mary; Novak, Mark; Petersen, Jeannine; Mead, Paul; Kingry, Luke; Weinburke, Matthew; Buttke, Danielle; Hacker, Gregory; Tucker, James; Niemela, Michael; Jackson, Bryan; Padgett, Kerry; Liebman, Kelly; Vugia, Duc

    2016-01-01

    In August 2015, plague was diagnosed for 2 persons who had visited Yosemite National Park in California, USA. One case was septicemic and the other bubonic. Subsequent environmental investigation identified probable locations of exposure for each patient and evidence of epizootic plague in other areas of the park. Transmission of Yersinia pestis was detected by testing rodent serum, fleas, and rodent carcasses. The environmental investigation and whole-genome multilocus sequence typing of Y. pestis isolates from the patients and environmental samples indicated that the patients had been exposed in different locations and that at least 2 distinct strains of Y. pestis were circulating among vector–host populations in the area. Public education efforts and insecticide applications in select areas to control rodent fleas probably reduced the risk for plague transmission to park visitors and staff. PMID:27870634

  20. Prelude to the plague: public health and politics at America's Pacific gateway, 1899.

    Science.gov (United States)

    Barde, Robert

    2003-04-01

    San Francisco played a crucial in the formulation of American immigration policy vis-à-vis Asia in the late nineteenth and early twentieth centuries. During this period, it was often difficult to differentiate political struggles over the exclusion of Asians from other conflicts. This article examines one such arena: an acrimonious, well-documented argument in 1899 between Federal and various State and local authorities over the arrival of a Japanese passenger liner that may--or may not--have been carrying bubonic plague. Six months later, the plague unquestionably arrived, resulting in the well-known San Francisco plague epidemic of 1900 in which more that 110 people died. Reviewing the 1899 prelude, the public attitudes of the various health authorities, and the way the press reported health issues, collectively give some sense of that historical space where the regulation of public health, politics, and the immigration industry intersected and were fiercely contested.

  1. Investigation of and Response to 2 Plague Cases, Yosemite National Park, California, USA, 2015.

    Science.gov (United States)

    Danforth, Mary; Novak, Mark; Petersen, Jeannine; Mead, Paul; Kingry, Luke; Weinburke, Matthew; Buttke, Danielle; Hacker, Gregory; Tucker, James; Niemela, Michael; Jackson, Bryan; Padgett, Kerry; Liebman, Kelly; Vugia, Duc; Kramer, Vicki

    2016-12-01

    In August 2015, plague was diagnosed for 2 persons who had visited Yosemite National Park in California, USA. One case was septicemic and the other bubonic. Subsequent environmental investigation identified probable locations of exposure for each patient and evidence of epizootic plague in other areas of the park. Transmission of Yersinia pestis was detected by testing rodent serum, fleas, and rodent carcasses. The environmental investigation and whole-genome multilocus sequence typing of Y. pestis isolates from the patients and environmental samples indicated that the patients had been exposed in different locations and that at least 2 distinct strains of Y. pestis were circulating among vector-host populations in the area. Public education efforts and insecticide applications in select areas to control rodent fleas probably reduced the risk for plague transmission to park visitors and staff.

  2. Isolation and Suffering Related to Serious and Terminal Illness: Metaphors and Lessons From Albert Camus' Novel, The Plague.

    Science.gov (United States)

    Tuffuor, Akosua N; Payne, Richard

    2017-09-01

    Health care providers have much to learn from Albert Camus' great novel, The Plague. The Plague tells the story of a bubonic plague epidemic through the lens of doctor-narrator Rieux. In addition to Rieux, this essay also focuses on the perspective of Father Paneloux, a Jesuit priest, who provides important religious commentary on the epidemic, before falling victim to it and dying. Camus' masterful engagement of the metaphor of isolation and its profound impact on suffering emphasizes the important role of community and spiritual perspectives of patients and providers in coping with serious illness, death, and dying. The Plague is relevant today, particularly given the challenges of distancing, alienation, and isolation imposed by not only disease but also by technology and clinical and administrative practices that have unintended consequences of incentivizing separation between patient and healer, thus engendering greater stress and suffering in both. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  3. Plague in Mongolia.

    Science.gov (United States)

    Galdan, Bolormaa; Baatar, Undraa; Molotov, Baigalmaa; Dashdavaa, Otgonbaatar

    2010-01-01

    Mongolia is a country of Central Asia that occupies 1,564,116 km(2) and has a population of 2.7 million people. The geography of Mongolia is varied and has a continental climate. Plague, caused by the bacterium Yersinia pestis, is enzootic in wild rodent populations over large rural areas of Mongolia. Natural plague foci have occurred over 28.3% of Mongolia, and 47.1% of these foci are highly active. Highly active plague foci exist mainly in the western part of Mongolia. A total of 27% of all plague cultures were isolated from ectoparasites of 12 species of endemic mammals and 1 species of bird. Most plague cultures isolated from ectoparasites of mammals were from fleas (91.5%). The majority of cultures isolated from fleas were from marmot fleas (64.5% of all fleas). The marmot flea (Oropsylla silantiewi) is considered the primary vector of plague. Human cases of plague have been recorded in Mongolia since 1897 and more than 3000 plague cultures were isolated from natural foci. Plague foci occur between 50 degrees 00-43 degrees 00 longitude and 88 degrees 00-120 degrees 00 latitude and at altitudes between 640 and 3500 m.

  4. Enzootic plague foci, Algeria

    Directory of Open Access Journals (Sweden)

    M.A. Malek

    2015-03-01

    Full Text Available In Algeria, PCR sequencing of pla, glpD and rpoB genes found Yersinia pestis in 18/237 (8% rodents of five species, including Apodemus sylvaticus, previously undescribed as pestiferous; and disclosed three new plague foci. Multiple spacer typing confirmed a new Orientalis variant. Rodent survey should be reinforced in this country hosting reemerging plague.

  5. Protect Yourself from Plague

    Science.gov (United States)

    ... rodents. Plague can also infect humans and their pets. How do people get plague? • • Bites of infected fleas • • Touching or ... be treated successfully with antibiotics, but an infected person must be treated ... your pets 1. Eliminate nesting places for rodents around homes, ...

  6. Mortality risk factors show similar trends in modern and historic populations exposed to plague.

    Science.gov (United States)

    Rubini, Mauro; Gualdi-Russo, Emanuela; Manzon, Vanessa S; Rinaldo, Natascia; Bianucci, Raffaella

    2016-05-31

    Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered. The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted. The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults). Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

  7. Mapping risk of plague in Qinghai-Tibetan Plateau, China.

    Science.gov (United States)

    Qian, Quan; Zhao, Jian; Fang, Liqun; Zhou, Hang; Zhang, Wenyi; Wei, Lan; Yang, Hong; Yin, Wenwu; Cao, Wuchun; Li, Qun

    2014-07-10

    Qinghai-Tibetan Plateau of China is known to be the plague endemic region where marmot (Marmota himalayana) is the primary host. Human plague cases are relatively low incidence but high mortality, which presents unique surveillance and public health challenges, because early detection through surveillance may not always be feasible and infrequent clinical cases may be misdiagnosed. Based on plague surveillance data and environmental variables, Maxent was applied to model the presence probability of plague host. 75% occurrence points were randomly selected for training model, and the rest 25% points were used for model test and validation. Maxent model performance was measured as test gain and test AUC. The optimal probability cut-off value was chosen by maximizing training sensitivity and specificity simultaneously. We used field surveillance data in an ecological niche modeling (ENM) framework to depict spatial distribution of natural foci of plague in Qinghai-Tibetan Plateau. Most human-inhabited areas at risk of exposure to enzootic plague are distributed in the east and south of the Plateau. Elevation, temperature of land surface and normalized difference vegetation index play a large part in determining the distribution of the enzootic plague. This study provided a more detailed view of spatial pattern of enzootic plague and human-inhabited areas at risk of plague. The maps could help public health authorities decide where to perform plague surveillance and take preventive measures in Qinghai-Tibetan Plateau.

  8. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; van der Kleij, D.; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    Yersinia pestis, the Gram-negative bacterial agent of plague, is a zoonotic pathogen that primarily infects wild rodents and is transmitted by fleas. Y. pestis is one of the most invasive and virulent bacterial pathogens and has caused devastating pandemics, including the Black Death of 14th century

  9. The NlpD lipoprotein is a novel Yersinia pestis virulence factor essential for the development of plague.

    Directory of Open Access Journals (Sweden)

    Avital Tidhar

    Full Text Available Yersinia pestis is the causative agent of plague. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the pcm gene was disrupted. In the present study, we investigated the expression and the role of pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y. pestis, nlpD expression is controlled from elements residing within the upstream genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm locus that is essential for Y. pestis virulence. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD(50 of at least 10(7 cfu for subcutaneous and airway routes of infection. The mutant was unable to colonize mouse organs following infection. The filamented morphology of the nlpD mutant indicates that NlpD is involved in cell separation; however, deletion of nlpD did not affect in vitro growth rate. Trans-complementation experiments with the Y. pestis nlpD gene restored virulence and all other phenotypic defects. Finally, we demonstrated that subcutaneous administration of the nlpD mutant could protect animals against bubonic and primary pneumonic plague. Taken together, these results demonstrate that Y. pestis NlpD is a novel virulence factor essential for the development of bubonic and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype live vaccine strain in immunogenicity and in conferring effective protective immunity. Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague.

  10. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    Science.gov (United States)

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Outbreak of Plague in a High Malaria Endemic Region - Nyimba District, Zambia, March-May 2015.

    Science.gov (United States)

    Sinyange, Nyambe; Kumar, Ramya; Inambao, Akatama; Moonde, Loveness; Chama, Jonathan; Banda, Mapopa; Tembo, Elliot; Nsonga, Beron; Mwaba, John; Fwoloshi, Sombo; Musokotwane, Kebby; Chizema, Elizabeth; Kapin'a, Muzala; Hang'ombe, Benard Mudenda; Baggett, Henry C; Hachaambwa, Lottie

    2016-08-12

    Outbreaks of plague have been recognized in Zambia since 1917 (1). On April 10, 2015, Zambia's Ministry of Health was notified by the Eastern Provincial Medical Office of possible bubonic plague cases in Nyimba District. Eleven patients with acute fever and cervical lymphadenopathy had been evaluated at two rural health centers during March 28-April 9, 2015; three patients died. To confirm the outbreak and develop control measures, the Zambia Ministry of Health's Field Epidemiology Training Program (ZFETP) conducted epidemiologic and laboratory investigations in partnership with the University of Zambia's schools of Medicine and Veterinary Medicine and the provincial and district medical offices. Twenty-one patients with clinically compatible plague were identified, with symptom onset during March 26-May 5, 2015. The median age was 8 years, and all patients were from the same village. Blood specimens or lymph node aspirates from six (29%) patients tested positive for Yersinia pestis by polymerase chain reaction (PCR). There is an urgent need to improve early identification and treatment of plague cases. PCR is a potential complementary tool for identifying plague, especially in areas with limited microbiologic capacity. Twelve (57%) patients, including all six with PCR-positive plague and all three who died, also tested positive for malaria by rapid diagnostic test (RDT). Plague patients coinfected with malaria might be misdiagnosed as solely having malaria, and appropriate antibacterial treatment to combat plague might not be given, increasing risk for mortality. Because patients with malaria might be coinfected with other pathogens, broad spectrum antibiotic treatment to cover other pathogens is recommended for all children with severe malaria, until a bacterial infection is excluded.

  12. Niche modeling predictions of the potential distribution of Marmota himalayana, the host animal of plague in Yushu County of Qinghai

    Directory of Open Access Journals (Sweden)

    Liang Lu

    2016-02-01

    Full Text Available Abstract Background After the earthquake on 14, April 2010 at Yushu in China, a plague epidemic hosted by Himalayan marmot (Marmota himalayana became a major public health concern during the reconstruction period. A rapid assessment of the distribution of Himalayan marmot in the area was urgent. The aims of this study were to analyze the relationship between environmental factors and the distribution of burrow systems of the marmot and to predict the distribution of marmots. Methods Two types of marmot burrows (hibernation and temporary in Yushu County were investigated from June to September in 2011. The location of every burrow was recorded with a global positioning system receiver. An ecological niche model was used to determine the relationship between the burrow occurrence data and environmental variables, such as land surface temperature (LST in winter and summer, normalized difference vegetation index (NDVI in winter and summer, elevation, and soil type. The predictive accuracies of the models were assessed by the area under the curve of the receiving operator curve. Results The models for hibernation and temporary burrows both performed well. The contribution orders of the variables were LST in winter and soil type, NDVI in winter and elevation for the hibernation burrow model, and LST in summer, NDVI in summer, soil type and elevation in the temporary burrow model. There were non-linear relationships between the probability of burrow presence and LST, NDVI and elevation. LST of 14 and 23 °C, NDVI of 0.22 and 0.60, and 4100 m were inflection points. A substantially higher probability of burrow presence was observed in swamp soil and dark felty soil than in other soil types. The potential area for hibernation burrows was 5696 km2 (37.7 % of Yushu County, and the area for temporary burrows was 7711 km2 (51.0 % of Yushu County. Conclusions The results suggested that marmots preferred warm areas with relatively low altitudes and good

  13. Ecology of Yersinia pestis and the Epidemiology of Plague.

    Science.gov (United States)

    Dubyanskiy, Vladimir M; Yeszhanov, Aidyn B

    2016-01-01

    This chapter summarizes information about the natural foci of plague in the world. We describe the location, main hosts, and vectors of Yersinia pestis. The ecological features of the hosts and vectors of plague are listed, including predators - birds and mammals and their role in the epizootic. The epizootic process in plague and the factors affecting the dynamics of epizootic activity of natural foci of Y. pestis are described in detail. The mathematical models of the epizootic process in plague and predictive models are briefly described. The most comprehensive list of the hosts and vectors of Y. pestis in the world is presented as well.

  14. Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in Madagascar.

    Science.gov (United States)

    Ratsitorahina, M; Chanteau, S; Rahalison, L; Ratsifasoamanana, L; Boisier, P

    2000-01-08

    Plague is a re-emerging disease and pneumonic plague is the most feared clinical form. We describe a well-documented outbreak of pneumonic plague in Madagascar. Field epidemiological data were collected. Biological tests (microscopy, culture of Yersinia pestis, F1 antigen ELISA and dipstick assays, IgG anti-F1 ELISA) were done on sputum, serum, or necropsy samples. The infection rate among 154 contacts was assessed by anti-F1 serological techniques. The index case was a bubonic patient with a secondary lung infection, who contaminated a traditional healer and his family. Funeral ceremonies and attendance on patients contaminated other villagers. In total 18 cases were recorded, and eight died. F1 antigen could be detected in sputum by ELISA and dipstick tests as early as the second day after the onset of the symptoms and also 48 h after treatment. Among the contact population 13 of 154 (8.4%) have been exposed to the plague bacillus (symptomless or latent infections). The F1 dipstick assay on sputum is an invaluable diagnostic tool for pneumonic plague. Treatment of patients and chemoprophylaxis of contacts were efficient in stopping the epidemic.

  15. [Resurgence of the plague in the Ikongo district of Madagascar in 1998. 2. Reservoirs and vectors implicated].

    Science.gov (United States)

    Duplantier, J M; Duchemin, J B; Ratsitorahina, M; Rahalison, L; Chanteau, S

    2001-05-01

    Our survey of mammals and fleas arose as a result of an outbreak of bubonic plague at an usually low altitude in the Ikongo district (Madagascar), while a previous study had found anti-F1 antibodies in an endemic hedgehog. Animals were sampled with live traps in two hamlets (Antanambao-Vohidrotra, 540 m alt. and Ambalagoavy, 265 m alt.) and with pitfall traps in a neighbouring forest (750 m alt.). Rat fleas were collected by brushing the fur and free-living fleas by use of light traps. The introduced shrew Suncus murinus was found only in the village of Ambalagoavy while the black rat (Rattus rattus) was found in all three sites and the only seropositive rat was caught at Antanambao-Vohidrotra. In contrast, among the Tenrecidae (endemic shrews and hedgehogs) found in the forest near the first village, four animals were found seropositive for anti-F1 antibodies. One of them was carrying the endemic flea Paractenopsyllus pauliani, not yet reported as a vector of plague. The endemic vector of plague, Synopsyllus fonquerniei, was found only in the first village of Antanambao-Vohidrotra, and the cosmopolite flea Xenopsylla cheopis only in Ambalagoavy. Although no Yersinia pestis could be isolated and no F1-antigen could be detected in these animals, we found evidence of the recent transmission of plague in Antanambao-Vohidrotra and the nearby forest, but not in Ambalagoavy. These data corroborate with the sylvatic plague cycle hypothesis in Madagascar and its involvement in the outcome of the bubonic plague outbreak in this district.

  16. [The Antonine plague].

    Science.gov (United States)

    Haas, Charles

    2006-01-01

    During the reign of Marcus Aurelius, the Roman Empire was struck by a long and destructive epidemic. It began in Mesopotamia in late AD 165 or early AD 166 during Verus' Parthian campaign, and quickly spread to Rome. It lasted at least until the death of Marcus Aurelius in AD 180 and likely into the early part of Commodus' reign. Its victims were "innumerable". Galen had first-hand knowledge of the disease. He was in Rome when the plague reached the city in AD 166. He was also present during an outbreak among troops stationed at Aquileia during the winter of AD 168-169. His references to the plague are scattered and brief but enough information is available to firmly identify the plague as smallpox. His description of the exanthema is fairly typical of the smallpox rash, particularly in the hemorrhagic phase of the disease.

  17. Predicting Potential Risk Areas of Human Plague for the Western Usambara Mountains, Lushoto District, Tanzania

    Science.gov (United States)

    Neerinckx, Simon; Peterson, A. Townsend; Gulinck, Hubert; Deckers, Jozef; Kimaro, Didas; Leirs, Herwig

    2010-01-01

    A natural focus of plague exists in the Western Usambara Mountains of Tanzania. Despite intense research, questions remain as to why and how plague emerges repeatedly in the same suite of villages. We used human plague incidence data for 1986–2003 in an ecological-niche modeling framework to explore the geographic distribution and ecology of human plague. Our analyses indicate that plague occurrence is related directly to landscape-scale environmental features, yielding a predictive understanding of one set of environmental factors affecting plague transmission in East Africa. Although many environmental variables contribute significantly to these models, the most important are elevation and Enhanced Vegetation Index derivatives. Projections of these models across broader regions predict only 15.5% (under a majority-rule threshold) or 31,997 km2 of East Africa as suitable for plague transmission, but they successfully anticipate most known foci in the region, making possible the development of a risk map of plague. PMID:20207880

  18. Predicting potential risk areas of human plague for the Western Usambara Mountains, Lushoto District, Tanzania.

    Science.gov (United States)

    Neerinckx, Simon; Peterson, A Townsend; Gulinck, Hubert; Deckers, Jozef; Kimaro, Didas; Leirs, Herwig

    2010-03-01

    A natural focus of plague exists in the Western Usambara Mountains of Tanzania. Despite intense research, questions remain as to why and how plague emerges repeatedly in the same suite of villages. We used human plague incidence data for 1986-2003 in an ecological-niche modeling framework to explore the geographic distribution and ecology of human plague. Our analyses indicate that plague occurrence is related directly to landscape-scale environmental features, yielding a predictive understanding of one set of environmental factors affecting plague transmission in East Africa. Although many environmental variables contribute significantly to these models, the most important are elevation and Enhanced Vegetation Index derivatives. Projections of these models across broader regions predict only 15.5% (under a majority-rule threshold) or 31,997 km(2) of East Africa as suitable for plague transmission, but they successfully anticipate most known foci in the region, making possible the development of a risk map of plague.

  19. The Second Plague Pandemic in the Golden Horde and Its Consequences

    Directory of Open Access Journals (Sweden)

    T.F. Khaydarov

    2014-12-01

    Full Text Available The article reviews the reasons for origin and consequences of spreading for the second plague pandemic in the Golden Horde. By applying scientific data from biology, climatology, medicine, and history, authors come to a conclusion that a large number of natural plague pestholes existed initially in the Ulus of Jochi. Numerous historical sources mentioned plague outbreaks but all of them were of purely local character. The bubonic type of plague characterized by a longer period of illness and an insignificant number of lethal episodes was spread more widely. In the mid-40s of the 14th century a new form of disease, the lung plague, came into existence. It was corpse blackening of the deceased from this type of plague that gave name to the whole pandemic – the “Black Death”. The speed of its progress and spreading significantly exceeded those of the bubonic type and 100% of mortality was recorded among the diseased. However, as historical data show, the outbreak of the lung plague continued in the territory of the Golden Horde from 1346 to 1349. In their article authors prove that one of the most important reasons for the emergence of the lung type was the change in migration flows of Eurasian rodents caused by depletion of nutritional resources in the steppe and serious climatic changes. All other outbreaks of the Black Death are viewed as continuation of the first wave of the disease and their emergence is explained through activity of two natural pestholes (the Relict North-Western and the Lower Volga ones. Consequences of the the first wave were much less substantial for the Ulus of Jochi than those of the following outbreaks (in 1364, 1374, and 1395. The main consequences of the next waves of the disease were: final establishment of 4 political centers (Grand Duchy of Moscow, the Bulgar and the Crimean uluses, and the Blue Horde striving for political leadership in the territory of the former Golden Horde; establishment of a new ethnic

  20. Mountain plover responses to plague in Montana.

    Science.gov (United States)

    Dinsmore, Stephen J; Smith, Mark D

    2010-01-01

    Plague is a bacterial (Yersinia pestis) disease that causes epizootic die-offs in black-tailed prairie dog (Cynomys ludovicianus) populations in the North American Great Plains. Through their grazing and burrowing, prairie dogs modify vegetation and landscape structure on their colonies in ways that affect other grassland species. Plague epizootics on prairie dog colonies can have indirect effects on species associated with colonies. The mountain plover (Charadrius montanus) preferentially nests on black-tailed prairie dog colonies and is thus negatively impacted by the loss of prairie dogs. We studied the effects of plague and colony spatial characteristics on the occupancy of 81 prairie dog colonies by nesting plovers in Phillips County, Montana, during a 13-year period (1995-2007). We used a robust design patch occupancy model to investigate how colony occupancy and extinction and colonization rates were affected by plague history, colony size, and colony shape. Here extinction and colonization rates refer to the probability that a colony loses/gains plovers in a subsequent nesting season, given that it had/lacked plovers in that breeding season. Colony occupancy was best explained by a model with no annual variation or plague effects. Colony extinction rates were driven by a combination of a quadratic of colony area, a 3-year plague response, and a measure of colony shape. Conversely, colonization rates were best explained by a model with a 4-year plague response. The estimated annual proportion of colonies occupied by plovers was 0.75 (95% confidence interval = 0.57-0.87). Estimated extinction probability ranged from a low of 0.07 (standard error [SE] = 0.02) in 2002 to a high of 0.25 (SE = 0.03) in 1995; colonization probability ranged from 0.24 (SE = 0.05) in 2006 to 0.35 (SE = 0.05) in 2000. Our results highlight how a bird that depends on prairie dogs for nesting habitat responds to plague history and other spatial characteristics of the colony. Ultimately

  1. Plague in Yosemite

    Centers for Disease Control (CDC) Podcasts

    2017-03-23

    Dr. Vicki Kramer, with the California Department of Public Health, discusses two cases of plague in Yosemite National Park.  Created: 3/23/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/23/2017.

  2. Plague in Uganda

    Centers for Disease Control (CDC) Podcasts

    2018-01-25

    Dr. Paul Mead, a medical officer at CDC, discusses his article on Plague in Uganda.  Created: 1/25/2018 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/25/2018.

  3. Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

    Directory of Open Access Journals (Sweden)

    Cristi L. Galindo

    2009-01-01

    Full Text Available We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT Y. pestis CO92 and its Braun lipoprotein (Δlpp mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS- associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague.

  4. Plague: history and contemporary analysis.

    Science.gov (United States)

    Raoult, Didier; Mouffok, Nadjet; Bitam, Idir; Piarroux, Renaud; Drancourt, Michel

    2013-01-01

    Plague has caused ravaging outbreaks, including the Justinian plague and the "black death" in the Middle Ages. The causative agents of these outbreaks have been confirmed using modern molecular tests. The vector of plague during pandemics remains the subject of controversy. Nowadays, plague must be suspected in all areas where plague is endemic in rodents when patients present with adenitis or with pneumonia with a bloody expectorate. Diagnosis is more difficult in the situation of the reemergence of plague, as in Algeria for example, told by the first physician involved in that outbreak (NM). When in doubt, it is preferable to prescribe treatment with doxycycline while waiting for the test results because of the risk of fatality in individuals with plague. The typical bubo is a type of adenitis that is painful, red and nonfluctuating. The diagnosis is simple when microbiological analysis is conducted. Plague is a likely diagnosis when one sees gram-negative bacilli in lymph node aspirate or biopsy samples. Yersinia pestis grows very easily in blood cultures and is easy to identify by biochemical tests and MALDI-TOF mass spectrometry. Pneumonic plague and septicemic plague without adenitis are difficult to diagnose, and these diagnoses are often made by chance or retrospectively when cases are not part of an epidemic or related to another specific epidemiologic context. The treatment of plague must be based on gentamicin or doxycycline. Treatment with one of these antibiotics must be started as soon as plague is suspected. Analysis of past plague epidemics by using modern laboratory tools illustrated the value of epidemic buboes for the clinical diagnosis of plague; and brought new concepts regarding its transmission by human ectoparasites. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  5. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach.

  6. Predicting Potential Risk Areas of Human Plague for the Western Usambara Mountains, Lushoto District, Tanzania

    DEFF Research Database (Denmark)

    Neerinckx, Simon; Peterson, A Townsend; Gulinck, Hubert

    2010-01-01

    A natural focus of plague exists in the Western Usambara Mountains of Tanzania. Despite intense research, questions remain as to why and how plague emerges repeatedly in the same suite of villages. We used human plague incidence data for 1986-2003 in an ecological-niche modeling framework...

  7. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Science.gov (United States)

    Welford, Mark R; Bossak, Brian H

    2009-12-22

    Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues") and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  8. Validation of inverse seasonal peak mortality in medieval plagues, including the Black Death, in comparison to modern Yersinia pestis-variant diseases.

    Directory of Open Access Journals (Sweden)

    Mark R Welford

    Full Text Available BACKGROUND: Recent studies have noted myriad qualitative and quantitative inconsistencies between the medieval Black Death (and subsequent "plagues" and modern empirical Y. pestis plague data, most of which is derived from the Indian and Chinese plague outbreaks of A.D. 1900+/-15 years. Previous works have noted apparent differences in seasonal mortality peaks during Black Death outbreaks versus peaks of bubonic and pneumonic plagues attributed to Y. pestis infection, but have not provided spatiotemporal statistical support. Our objective here was to validate individual observations of this seasonal discrepancy in peak mortality between historical epidemics and modern empirical data. METHODOLOGY/PRINCIPAL FINDINGS: We compiled and aggregated multiple daily, weekly and monthly datasets of both Y. pestis plague epidemics and suspected Black Death epidemics to compare seasonal differences in mortality peaks at a monthly resolution. Statistical and time series analyses of the epidemic data indicate that a seasonal inversion in peak mortality does exist between known Y. pestis plague and suspected Black Death epidemics. We provide possible explanations for this seasonal inversion. CONCLUSIONS/SIGNIFICANCE: These results add further evidence of inconsistency between historical plagues, including the Black Death, and our current understanding of Y. pestis-variant disease. We expect that the line of inquiry into the disputed cause of the greatest recorded epidemic will continue to intensify. Given the rapid pace of environmental change in the modern world, it is crucial that we understand past lethal outbreaks as fully as possible in order to prepare for future deadly pandemics.

  9. High-Throughput, Signature-Tagged Mutagenic Approach To Identify Novel Virulence Factors of Yersinia pestis CO92 in a Mouse Model of Infection

    Science.gov (United States)

    Ponnusamy, Duraisamy; Fitts, Eric C.; Erova, Tatiana E.; Kozlova, Elena V.; Kirtley, Michelle L.; Tiner, Bethany L.; Andersson, Jourdan A.

    2015-01-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  10. Molecular history of plague.

    Science.gov (United States)

    Drancourt, M; Raoult, D

    2016-11-01

    Plague, a deadly zoonose caused by the bacterium Yersinia pestis, has been firmly documented in 39 historical burial sites in Eurasia that date from the Bronze Age to two historical pandemics spanning the 6th to 18th centuries. Palaeomicrobiologic data, including gene and spacer sequences, whole genome sequences and protein data, confirmed that two historical pandemics swept over Europe from probable Asian sources and possible two-way-ticket journeys back from Europe to Asia. These investigations made it possible to address questions regarding the potential sources and routes of transmission by completing the standard rodent and rodent-flea transmission scheme. This suggested that plague was transmissible by human ectoparasites such as lice, and that Y. pestis was able to persist for months in the soil, which is a source of reinfection for burrowing mammals. The analyses of seven complete genome sequences from the Bronze Age indicated that Y. pestis was probably not an ectoparasite-borne pathogen in these populations. Further analyses of 14 genomes indicated that the Justinian pandemic strains may have formed a clade distinct from the one responsible for the second pandemic, spanning in Y. pestis branch 1, which also comprises the third pandemic strains. Further palaeomicrobiologic studies must tightly connect with historical and anthropologic studies to resolve questions regarding the actual sources of plague in ancient populations, alternative routes of transmission and resistance traits. Answering these questions will broaden our understanding of plague epidemiology so we may better face the actuality of this deadly infection in countries where it remains epidemic. Copyright © 2016. Published by Elsevier Ltd.

  11. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    Science.gov (United States)

    Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2012-01-01

    Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  12. An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Anne Derbise

    Full Text Available BACKGROUND: Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. METHODOLOGY AND PRINCIPAL FINDINGS: The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells and the mucosal levels (IgA and Th17 cells. A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50 of the fully virulent Y. pestis CO92 strain and 94% against a high challenge dose (3,300×LD(50. Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. CONCLUSIONS AND SIGNIFICANCE: The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

  13. Low cost, low tech SNP genotyping tools for resource-limited areas: Plague in Madagascar as a model.

    Science.gov (United States)

    Mitchell, Cedar L; Andrianaivoarimanana, Voahangy; Colman, Rebecca E; Busch, Joseph; Hornstra-O'Neill, Heidie; Keim, Paul S; Wagner, David M; Rajerison, Minoarisoa; Birdsell, Dawn N

    2017-12-01

    Genetic analysis of pathogenic organisms is a useful tool for linking human cases together and/or to potential environmental sources. The resulting data can also provide information on evolutionary patterns within a targeted species and phenotypic traits. However, the instruments often used to generate genotyping data, such as single nucleotide polymorphisms (SNPs), can be expensive and sometimes require advanced technologies to implement. This places many genotyping tools out of reach for laboratories that do not specialize in genetic studies and/or lack the requisite financial and technological resources. To address this issue, we developed a low cost and low tech genotyping system, termed agarose-MAMA, which combines traditional PCR and agarose gel electrophoresis to target phylogenetically informative SNPs. To demonstrate the utility of this approach for generating genotype data in a resource-constrained area (Madagascar), we designed an agarose-MAMA system targeting previously characterized SNPs within Yersinia pestis, the causative agent of plague. We then used this system to genetically type pathogenic strains of Y. pestis in a Malagasy laboratory not specialized in genetic studies, the Institut Pasteur de Madagascar (IPM). We conducted rigorous assay performance validations to assess potential variation introduced by differing research facilities, reagents, and personnel and found no difference in SNP genotyping results. These agarose-MAMA PCR assays are currently employed as an investigative tool at IPM, providing Malagasy researchers a means to improve the value of their plague epidemiological investigations by linking outbreaks to potential sources through genetic characterization of isolates and to improve understanding of disease ecology that may contribute to a long-term control effort. The success of our study demonstrates that the SNP-based genotyping capacity of laboratories in developing countries can be expanded with manageable financial cost for

  14. Plague and Climate: Scales Matter

    Science.gov (United States)

    Ben Ari, Tamara; Neerinckx, Simon; Gage, Kenneth L.; Kreppel, Katharina; Laudisoit, Anne; Leirs, Herwig; Stenseth, Nils Chr.

    2011-01-01

    Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations. PMID:21949648

  15. Plague in Tanzania: an overview.

    Science.gov (United States)

    Ziwa, Michael H; Matee, Mecky I; Hang'ombe, Bernard M; Lyamuya, Eligius F; Kilonzo, Bukheti S

    2013-10-01

    Human plague remains a public health concern in Tanzania despite its quiescence in most foci for years, considering the recurrence nature of the disease. Despite the long-standing history of this problem, there have not been recent reviews of the current knowledge on plague in Tanzania. This work aimed at providing a current overview of plague in Tanzania in terms of its introduction, potential reservoirs, possible causes of plague persistence and repeated outbreaks in the country. Plague is believed to have been introduced to Tanzania from the Middle East through Uganda with the first authentication in 1886. Xenopsylla brasiliensis, X. cheopis, Dinopsyllus lypusus, and Pulex irritans are among potential vectors while Lophuromys spp, Praomys delectorum, Graphiurus murinus, Lemniscomys striatus, Mastomys natalensis, and Rattus rattus may be the potential reservoirs. Plague persistence and repeated outbreaks in Tanzania are likely to be attributable to a complexity of factors including cultural, socio-economical, environmental and biological. Minimizing or preventing people's proximity to rodents is probably the most effective means of preventing plague outbreaks in humans in the future. In conclusion, much has been done on plague diagnosis in Tanzania. However, in order to achieve new insights into the features of plague epidemiology in the country, and to reorganize an effective control strategy, we recommend broader studies that will include the ecology of the pathogen, vectors and potential hosts, identifying the reservoirs, dynamics of infection and landscape ecology.

  16. Low cost, low tech SNP genotyping tools for resource-limited areas: Plague in Madagascar as a model.

    Directory of Open Access Journals (Sweden)

    Cedar L Mitchell

    2017-12-01

    Full Text Available Genetic analysis of pathogenic organisms is a useful tool for linking human cases together and/or to potential environmental sources. The resulting data can also provide information on evolutionary patterns within a targeted species and phenotypic traits. However, the instruments often used to generate genotyping data, such as single nucleotide polymorphisms (SNPs, can be expensive and sometimes require advanced technologies to implement. This places many genotyping tools out of reach for laboratories that do not specialize in genetic studies and/or lack the requisite financial and technological resources. To address this issue, we developed a low cost and low tech genotyping system, termed agarose-MAMA, which combines traditional PCR and agarose gel electrophoresis to target phylogenetically informative SNPs.To demonstrate the utility of this approach for generating genotype data in a resource-constrained area (Madagascar, we designed an agarose-MAMA system targeting previously characterized SNPs within Yersinia pestis, the causative agent of plague. We then used this system to genetically type pathogenic strains of Y. pestis in a Malagasy laboratory not specialized in genetic studies, the Institut Pasteur de Madagascar (IPM. We conducted rigorous assay performance validations to assess potential variation introduced by differing research facilities, reagents, and personnel and found no difference in SNP genotyping results. These agarose-MAMA PCR assays are currently employed as an investigative tool at IPM, providing Malagasy researchers a means to improve the value of their plague epidemiological investigations by linking outbreaks to potential sources through genetic characterization of isolates and to improve understanding of disease ecology that may contribute to a long-term control effort.The success of our study demonstrates that the SNP-based genotyping capacity of laboratories in developing countries can be expanded with manageable

  17. The Formula of Plague Narratives

    DEFF Research Database (Denmark)

    Christensen, Jørgen Riber

    2015-01-01

    and fictional, of epidemics. The samples include: Exodus, History of the Peloponnesian War, Samuel Pepys’ Diary, A Journal of the Plague Year, The Last Man, The Plague in Bergamo, Discipline and Punish: The Birth of the Prison, Doomsday, The Dead Zone, World War Z. An Oral History of the Zombie War, Pandemic...

  18. Human plague occurrences in Africa

    DEFF Research Database (Denmark)

    Neerinckx, Simon; Bertherat, Eric; Leirs, Herwig

    2010-01-01

    Africa and Madagascar. We show that public health concerns regarding the current plague situation are justified and that the disease should not be neglected, despite the sometimes questionability of the numbers of cases. We conclude that improving plague surveillance strategies is absolutely necessary...

  19. Plague and other human infections caused by Yersinia species.

    Science.gov (United States)

    Putzker, M; Sauer, H; Sobe, D

    2001-01-01

    With an estimated 100 million victims, pandemically and epidemically occurring plague has been looked upon as a classical scourge of mankind during the last two millenia. Without treatment at least 50% of the affected individuals die from infection with Yersinia pestis, a bacterium belonging to the family of Enterobacteriaceae. The disease takes a fulminant course. After an incubation period of 2-6 days, bubonic plague primarily attacks one group of lymph nodes. The onset of pulmonic plague, transmitted by droplet infection, takes place within several hours and causes bronchopneumonia. Early recognition facilitates a promising antibiotic therapy with tetracycline, streptomycin or chloramphenicol. Human beings acquire the bacteria through bites of fleas from domestic rats in densely populated cities of countries with low hygienic standards, or sporadically in the open country from infected wild rodents. Laboratory procedure includes microscopy supplemented by immunofluorescence and cultivation of the bacterium from clinical material. Direct serology and PCR result in a fast detection of specific antigens or nucleotide sequences. Determination of serum antibodies is principally used for epidemiological investigation. Today, physicians in the civilized western world lack experience for the recognition of plague, and analytical techniques for diagnosis are only available in some specialized laboratories. Yersiniosis becomes primarily manifest as gastroenteritis caused by Yersinia enterocolitica or as pseudoappendicitis caused by Yersinia pseudotuberculosis and requires antibiotics only in severe septic cases. Different extraintestinal symptoms may be observed in dependence on the patient's HLA type and gender. The ubiquitous germ is mainly transmitted by the fecal-oral route via infected domestic or farm animals and contaminated food. The relevant virulence factors are encoded on a 70 kB plasmid common to all Yersinia species and strains that are human pathogens. The

  20. [The Justinian plague (part two). Influence of the epidemic on the rise of the Islamic Empire].

    Science.gov (United States)

    Sabbatani, Sergio; Manfredi, Roberto; Fiorino, Sirio

    2012-09-01

    The Islamic Empire started its tumultuous and rapid expansion from the year 622 A.D. (the year of Mohammed's Egira). This rapid growth coincided with the epidemic spread of the bubonic plague in the Middle East. Although a first epidemic event had been documented in the year 570 A.D. (pre-Islamic phase), in the Arabic peninsula, classically according to M.W. Dols five severe episodes of plague sub-epidemics are considered in the middle-eastern geographic area: the first occurred in 627 and 628 A.D., the fifth in 716 A.D.. Anyway, we may state that at the onset of Islam the geographic region including Egypt, Palestine, Syria, Iraq, and Iran was involved by endemic plague. In their work, on the ground of a literature review, the Authors describe the characteristics of the epidemic phenomenon, and analyze the how the plague affected the interpretation of Prophet's Koran and Hadits. The passive attitude demonstrated by many Muslims during early Islam was not shared by all believers, since others moved towards a more soft approach, which included the behaviour of the so called moving aside , when the contagion was of concern. The epidemic plague significantly contributed to the weakening of the Eastern Roman Empire, and the rapid decline of the Persian Empire, while during the early expansion phases of Islam, it indirectly favoured the nomadic Arab tribes which, moving on desert or semi-desert territories, succeeded in escaping the contagion more easily. Subsequently, when the Arab population became sedentary, after occupying the conquered cities, this initial advantage was significantly reduced.

  1. Lovastatin protects against experimental plague in mice.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

  2. Paltry past-precipitation: Predisposing prairie dogs to plague?

    Science.gov (United States)

    Eads, David; Biggins, Dean E.

    2017-01-01

    The plague bacterium Yersinia pestis was introduced to California in 1900 and spread rapidly as a sylvatic disease of mammalian hosts and flea vectors, invading the Great Plains in the United States by the 1930s to 1940s. In grassland ecosystems, plague causes periodic, devastating epizootics in colonies of black-tailed prairie dogs (Cynomys ludovicianus), sciurid rodents that create and maintain subterranean burrows. In doing so, plague inhibits prairie dogs from functioning as keystone species of grassland communities. The rate at which fleas transmit Y. pestis is thought to increase when fleas are abundant. Flea densities can increase during droughts when vegetative production is reduced and herbivorous prairie dogs are malnourished and have weakened defenses against fleas. Epizootics of plague have erupted frequently in prairie dogs during years in which precipitation was plentiful, and the accompanying cool temperatures might have facilitated the rate at which fleas transmitted Y. pestis. Together these observations evoke the hypothesis that transitions from dry-to-wet years provide conditions for plague epizootics in prairie dogs. Using generalized linear models, we analyzed a 24-year dataset on the occurrence of plague epizootics in 42 colonies of prairie dogs from Colorado, USA, 1982–2005. Of the 33 epizootics observed, 52% erupted during years with increased precipitation in summer. For the years with increased summer precipitation, if precipitation in the prior growing season declined from the maximum of 502 mm to the minimum of 200 mm, the prevalence of plague epizootics was predicted to increase 3-fold. Thus, reduced precipitation may have predisposed prairie dogs to plague epizootics when moisture returned. Biologists sometimes assume dry conditions are detrimental for plague. However, 48% of epizootics occurred during years in which precipitation was scarce in summer. In some cases, an increased abundance of fleas during dry years might

  3. Plague Outbreak in Libya, 2009, Unrelated to Plague in Algeria

    Science.gov (United States)

    Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric

    2013-01-01

    After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci. PMID:23347743

  4. Plague outbreak in Libya, 2009, unrelated to plague in Algeria.

    Science.gov (United States)

    Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric; Carniel, Elisabeth

    2013-02-01

    After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci.

  5. Plague Vaccines: Status and Future.

    Science.gov (United States)

    Sun, Wei

    2016-01-01

    Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y. pestis strain resistant to eight antibiotics bring out severe public health concerns. Therefore, prophylactic vaccination against this disease holds the brightest prospect for its long-term prevention. Here, we summarize the progress of the current vaccine development for counteracting plague.

  6. Plague and the Human Flea, Tanzania

    DEFF Research Database (Denmark)

    Laudisoit, Anne; Leirs, Herwig; Makundi, Rhodes H

    2007-01-01

    Domestic fleas were collected in 12 villages in the western Usambara Mountains in Tanzania. Of these, 7 are considered villages with high plague frequency, where human plague was recorded during at least 6 of the 17 plague seasons between 1986 and 2004. In the remaining 5 villages with low plague...... frequency, plague was either rare or unrecorded. Pulex irritans, known as the human flea, was the predominant flea species (72.4%) in houses. The density of P. irritans, but not of other domestic fleas, was significantly higher in villages with a higher plague frequency or incidence. Moreover, the P....... irritans index was strongly positively correlated with plague frequency and with the logarithmically transformed plague incidence. These observations suggest that in Lushoto District human fleas may play a role in plague epidemiology. These findings are of immediate public health relevance because...

  7. Identification of Chinese plague foci from long-term epidemiological data

    Science.gov (United States)

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  8. A Yersinia pestis lpxM-mutant live vaccine induces enhanced immunity against bubonic plague in mice and guinea pigs.

    Science.gov (United States)

    Feodorova, V A; Pan'kina, L N; Savostina, E P; Sayapina, L V; Motin, V L; Dentovskaya, S V; Shaikhutdinova, R Z; Ivanov, S A; Lindner, B; Kondakova, A N; Bystrova, O V; Kocharova, N A; Senchenkova, S N; Holst, O; Pier, G B; Knirel, Y A; Anisimov, A P

    2007-11-01

    The lpxM mutant of the live vaccine Yersinia pestis EV NIIEG strain synthesising a less toxic penta-acylated lipopolysaccharide was found to be avirulent in mice and guinea pigs, notably showing no measurable virulence in Balb/c mice which do retain some susceptibility to the parental strain itself. Twenty-one days after a single injection of the lpxM-mutant, 85-100% protection was achieved in outbred mice and guinea pigs, whereas a 43% protection rate was achieved in Balb/c mice given single low doses (10(3) to 2.5 x 10(4) CFU) of this vaccine. A subcutaneous challenge with 2000 median lethal doses (equal to 20,000 CFU) of fully virulent Y. pestis 231 strain, is a 6-10-fold higher dose than that which the EV NIIEG itself can protect against.

  9. Geographic distribution and ecological niche of plague in sub-Saharan Africa

    DEFF Research Database (Denmark)

    Neerinckx, Simon B; Peterson, Andrew T; Gulinck, Hubert

    2008-01-01

    predict a broad potential distributional area of plague occurrences across sub-Saharan Africa. General tests of model's transferability suggest that our model can anticipate the potential distribution of plague occurrences in Madagascar and northern Africa. However, generality and predictive ability tests...

  10. Frequently Asked Questions (FAQ) about Plague

    Science.gov (United States)

    ... Yersinia pestis ( Y. pestis ), a bacterium found in rodents and their fleas in many areas around the ... disease. Naturally occurring pneumonic plague is uncommon, although small outbreaks do occur. Both types of plague are ...

  11. Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge.

    Science.gov (United States)

    Branger, Christine G; Sun, Wei; Torres-Escobar, Ascención; Perry, Robert; Roland, Kenneth L; Fetherston, Jacqueline; Curtiss, Roy

    2010-12-16

    We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. [Tholozan and plague in Persia].

    Science.gov (United States)

    Mollaret, H H

    1998-09-01

    In Persia since 1858, Tholozan studied between 1870 and 1882 the plague foci of the iranian Kurdistan which shall be dealt a century later (1947-1963) with Dr. M. Baltazard and his co-workers from the Pasteur Institute of Teheran. Tholozan had already pointed out the localization of the disease in some well defined villages and gave a good clinical description mentioning the traces of flea bites on the patients skin. One knows nowadays that wild rodents (Meriones) are the storing places of the plague bacilli in the Kurdistan. Tholozan's observations confirmed by modern ones allow to consider him a great loïmologist of modern times.

  13. Red Plague Control Plan (RPCP)

    Science.gov (United States)

    Cooke, Robert W.

    2010-01-01

    SCOPE: Prescribes the minimum requirements for the control of cuprous / cupric oxide corrosion (a.k.a. Red Plague) of silver-coated copper wire, cable, and harness assemblies. PURPOSE: Targeted for applications where exposure to assembly processes, environmental conditions, and contamination may promote the development of cuprous / cupric oxide corrosion (a.k.a. Red Plague) in silver-coated copper wire, cable, and harness assemblies. Does not exclude any alternate or contractor-proprietary documents or processes that meet or exceed the baseline of requirements established by this document. Use of alternate or contractor-proprietary documents or processes shall require review and prior approval of the procuring NASA activity.

  14. Nonlinear effect of climate on plague during the third pandemic in China

    Science.gov (United States)

    Xu, Lei; Liu, Qiyong; Stige, Leif Chr.; Ben Ari, Tamara; Fang, Xiye; Chan, Kung-Sik; Wang, Shuchun; Stenseth, Nils Chr.; Zhang, Zhibin

    2011-01-01

    Over the years, plague has caused a large number of deaths worldwide and subsequently changed history, not the least during the period of the Black Death. Of the three plague pandemics, the third is believed to have originated in China. Using the spatial and temporal human plague records in China from 1850 to 1964, we investigated the association of human plague intensity (plague cases per year) with proxy data on climate condition (specifically an index for dryness/wetness). Our modeling analysis demonstrates that the responses of plague intensity to dry/wet conditions were different in northern and southern China. In northern China, plague intensity generally increased when wetness increased, for both the current and the previous year, except for low intensity during extremely wet conditions in the current year (reflecting a dome-shaped response to current-year dryness/wetness). In southern China, plague intensity generally decreased when wetness increased, except for high intensity during extremely wet conditions of the current year. These opposite effects are likely related to the different climates and rodent communities in the two parts of China: In northern China (arid climate), rodents are expected to respond positively to high precipitation, whereas in southern China (humid climate), high precipitation is likely to have a negative effect. Our results suggest that associations between human plague intensity and precipitation are nonlinear: positive in dry conditions, but negative in wet conditions. PMID:21646523

  15. Nonlinear effect of climate on plague during the third pandemic in China.

    Science.gov (United States)

    Xu, Lei; Liu, Qiyong; Stige, Leif Chr; Ben Ari, Tamara; Fang, Xiye; Chan, Kung-Sik; Wang, Shuchun; Stenseth, Nils Chr; Zhang, Zhibin

    2011-06-21

    Over the years, plague has caused a large number of deaths worldwide and subsequently changed history, not the least during the period of the Black Death. Of the three plague pandemics, the third is believed to have originated in China. Using the spatial and temporal human plague records in China from 1850 to 1964, we investigated the association of human plague intensity (plague cases per year) with proxy data on climate condition (specifically an index for dryness/wetness). Our modeling analysis demonstrates that the responses of plague intensity to dry/wet conditions were different in northern and southern China. In northern China, plague intensity generally increased when wetness increased, for both the current and the previous year, except for low intensity during extremely wet conditions in the current year (reflecting a dome-shaped response to current-year dryness/wetness). In southern China, plague intensity generally decreased when wetness increased, except for high intensity during extremely wet conditions of the current year. These opposite effects are likely related to the different climates and rodent communities in the two parts of China: In northern China (arid climate), rodents are expected to respond positively to high precipitation, whereas in southern China (humid climate), high precipitation is likely to have a negative effect. Our results suggest that associations between human plague intensity and precipitation are nonlinear: positive in dry conditions, but negative in wet conditions.

  16. [The complex plague--reconsiderations of an epidemic from the past].

    Science.gov (United States)

    Moseng, Ole Georg

    2007-12-13

    Speculations have arisen about the black plague in recent years - was it a disease caused by YERSINIA PESTIS: or something else? Extensive outbreaks in India in the 1890s have formed the basis for descriptions of the plague, both for those who believe that the medieval plagues and modern plague were different diseases and for those who claim that the plague has been one and the same disease throughout history. The plague was more or less defined as a disease in the 1890s, and the understanding of its clinical course and dissemination at the time has uncritically been understood as the general model for spreading of the plague. But plague is a many-faceted disease. It has spread to five continents in modern times, through an array of ecosystems and under widely different climatic conditions. It can also be passed on to man, and from one individual to another, in different ways. The biological conditions that prevailed in India have not been relevant for medieval Norway. The preconditions for spreading of plague epidemics of the past in a Nordic climate must therefore have been different. It can only be expected that contemporary descriptions of historic epidemics are different from those in modern times.

  17. Contribution of land use to rodent flea load distribution in the plague endemic area of Lushoto District, Tanzania.

    Science.gov (United States)

    Hieronimo, Proches; Kihupi, Nganga I; Kimaro, Didas N; Gulinck, Hubert; Mulungu, Loth S; Msanya, Balthazar M; Leirs, Herwig; Deckers, Jozef A

    2014-07-01

    Fleas associated with different rodent species are considered as the major vectors of bubonic plague, which is still rampant in different parts of the world. The objective of this study was to investigate the contribution of land use to rodent flea load distribution at fine scale in the plague endemic area of north-eastern Tanzania. Data was collected in three case areas namely, Shume, Lukozi and Mwangoi, differing in plague incidence levels. Data collection was carried out during both wet and dry seasons of 2012. Analysis of Variance and Boosted Regression Tree (BRT) statistical methods were used to clarify the relationships between fleas and specific land use characteristics. There was a significant variation (P ≤ 0.05) of flea indices in different land use types. Fallow and natural forest had higher flea indices whereas plantation forest mono-crop and mixed annual crops had the lowest flea indices among the aggregated land use types. The influence of individual land use types on flea indices was variable with fallow having a positive effect and land tillage showing a negative effect. The results also demonstrated a seasonal effect, part of which can be attributed to different land use practices such as application of pesticides, or the presence of grass strips around fields. These findings suggest that land use factors have a major influence on rodent flea abundance which can be taken as a proxy for plague infection risk. The results further point to the need for a comprehensive package that includes land tillage and crop type considerations on one hand and the associated human activities on the other, in planning and implementation of plague control interventions.

  18. Zoonoses As Ecological Entities: A Case Review of Plague.

    Science.gov (United States)

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

    2016-10-01

    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.

  19. Zoonoses As Ecological Entities: A Case Review of Plague.

    Directory of Open Access Journals (Sweden)

    Caio Graco Zeppelini

    2016-10-01

    Full Text Available 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.

  20. Plague in the genomic area.

    Science.gov (United States)

    Drancourt, M

    2012-03-01

    With plague being not only a subject of interest for historians, but still a disease of public health concern in several countries, mainly in Africa, there were hopes that analyses of the Yersinia pestis genomes would put an end to this deadly epidemic pathogen. Genomics revealed that Y. pestis isolates evolved from Yersinia pseudotuberculosis in Central Asia some millennia ago, after the acquisition of two Y. pestis-specific plasmids balanced genomic reduction parallel with the expansion of insertion sequences, illustrating the modern concept that, except for the acquisition of plasmid-borne toxin-encoding genes, the increased virulence of Y. pestis resulted from gene loss rather than gene acquisition. The telluric persistence of Y. pestis reminds us of this close relationship, and matters in terms of plague epidemiology. Whereas biotype Orientalis isolates spread worldwide, the Antiqua and Medievalis isolates showed more limited expansion. In addition to animal ectoparasites, human ectoparasites such as the body louse may have participated in this expansion and in devastating historical epidemics. The recent analysis of a Black Death genome indicated that it was more closely related to the Orientalis branch than to the Medievalis branch. Modern Y. pestis isolates grossly exhibit the same gene content, but still undergo micro-evolution in geographically limited areas by differing in the genome architecture, owing to inversions near insertion sequences and the stabilization of the YpfPhi prophage in Orientalis biotype isolates. Genomics have provided several new molecular tools for the genotyping and phylogeographical tracing of isolates and description of plague foci. However, genomics and post-genomics approaches have not yet provided new tools for the prevention, diagnosis and management of plague patients and the plague epidemics still raging in some sub-Saharan countries. © 2012 The Author. Clinical Microbiology and Infection © 2012 European Society of

  1. Are carnivores universally good sentinels of plague?

    Science.gov (United States)

    Brinkerhoff, R Jory; Collinge, Sharon K; Bai, Ying; Ray, Chris

    2009-10-01

    Sylvatic plague, caused by the bacterium Yersinia pestis, is a flea-borne disease that primarily affects rodents but has been detected in over 200 mammal species worldwide. Mammalian carnivores are routinely surveyed as sentinels of local plague activity, since they can present antibodies to Y. pestis infection but show few clinical signs. In Boulder County, Colorado, USA, plague epizootic events are episodic and occur in black-tailed prairie dogs. Enzootic hosts are unidentified as are plague foci. For three years, we systematically sampled carnivores in two distinct habitat types to determine whether carnivores may play a role in maintenance or transmission of Y. pestis and to identify habitats associated with increased plague prevalence. We sampled 83 individuals representing six carnivore species and found only two that had been exposed to Y. pestis. The low overall rate of plague exposure in carnivores suggests that plague may be ephemeral in this study system, and thus we cannot draw any conclusions regarding habitat-associated plague foci or temporal changes in plague activity. Plague epizootics involving prairie dogs were confirmed in this study system during two of the three years of this study, and we therefore suggest that the targeting carnivores to survey for plague may not be appropriate in all ecological systems.

  2. Epidemiological trends for human plague in Madagascar during the second half of the 20th century: a survey of 20,900 notified cases.

    Science.gov (United States)

    Migliani, René; Chanteau, Suzanne; Rahalison, Lila; Ratsitorahina, Maherisoa; Boutin, Jean Paul; Ratsifasoamanana, Lala; Roux, Jean

    2006-08-01

    To describe the principal characteristics and epidemiological trends for human plague in modern times based on the largest reported series of cases from the highly active Malagasy focus. We used a file of 20,900 notified cases of suspected plague, 4,473 of which were confirmed or probable, to carry out a statistical analysis of incidence and mortality rates and associated factors for 5-year periods from 1957 to 2001. Our analysis of trends showed (1) an increase in the incidence rate and the number of districts affected, (2) an increase in the proportion of bubonic forms (64.8-96.8%) at the expense of the pneumonic forms (35.2-3.2%) more frequent in elderly subjects and (3) a decrease in case fatality rate (CFR, 55.7-20.9%) associated with five factors: clinical form, season, province, urban/rural and period considered. The median age of patients was 14 years and more men than women were affected. Since the end of the 1980s, the incidence of plague in Madagascar has increased in both rural and urban areas, because of multiple socioeconomic and environmental factors. However, the plague mortality rate has tended to decrease, together with the frequency of pneumonic forms, because of the strengthening of control measures. Making dipstick tests for the rapid diagnosis of human cases and epizootics in rats available for health structures should make it possible to raise the alarm and to react rapidly, thereby further decreasing morbidity and CFR.

  3. Spread of plague among black-tailed prairie dogs is associated with colony spatial characteristics

    Science.gov (United States)

    Johnson, T.L.; Cully, J.F.; Collinge, S.K.; Ray, C.; Frey, C.M.; Sandercock, B.K.

    2011-01-01

    Sylvatic plague (Yersinia pestis) is an exotic pathogen that is highly virulent in black-tailed prairie dogs (Cynomys ludovicianus) and causes widespread colony losses and individual mortality rates >95%. We investigated colony spatial characteristics that may influence inter-colony transmission of plague at 3 prairie dog colony complexes in the Great Plains. The 4 spatial characteristics we considered include: colony size, Euclidean distance to nearest neighboring colony, colony proximity index, and distance to nearest drainage (dispersal) corridor. We used multi-state mark-recapture models to determine the relationship between these colony characteristics and probability of plague transmission among prairie dog colonies. Annual mapping of colonies and mark-recapture analyses of disease dynamics in natural colonies led to 4 main results: 1) plague outbreaks exhibited high spatial and temporal variation, 2) the site of initiation of epizootic plague may have substantially influenced the subsequent inter-colony spread of plague, 3) the long-term effect of plague on individual colonies differed among sites because of how individuals and colonies were distributed, and 4) colony spatial characteristics were related to the probability of infection at all sites although the relative importance and direction of relationships varied among sites. Our findings suggest that conventional prairie dog conservation management strategies, including promoting large, highly connected colonies, may need to be altered in the presence of plague. ?? 2011 The Wildlife Society.

  4. Una aproximación a las pestes y epidemias en la antigüedad = An approach to the plagues and epidemics in Ancient World

    Directory of Open Access Journals (Sweden)

    Enrique Gozalbes Cravioto

    2014-12-01

    Full Text Available En este artículo se estudian los principales episodios de pestes y epidemias que se produjeron en las civilizaciones de la antigüedad. Se analizan la gran peste de los hititas, en época del rey Mursili II (1321 a. C.-1295 a. C., la peste padecida por los filisteos (peste de Azoth, las epidemias padecidas por el ejército cartaginés en Sicilia (siglos V y IV a.C., la gran peste de Atenas en 439-429 a. C. (en la actualidad interpretada como tifus, las epidemias en la República romana de los siglos V y IV a. C., así como las epidemias padecidas por el imperio romano (en especial la peste de los Antoninos en el siglo II, y la de Cipriano en el siglo III, que se interpretan como viruela y sarampión. Finalmente se exponen datos sobre la peste padecida por Bizancio, en época del emperador Justiniano, que constituye ya, sin duda, el primer azote importante de la peste bubónica.This article examines the principal episodes of pest and epidemics that occurred in ancient civilizations. It discusses the great plague of the Hittites, in time of king Mursili II (1321-1295 B.C., the plague sufferend by the Philistines (Azoth Plague, the epidemics suffered by the Carthaginian army in Sicily (V and IV centuries B. C., the great pest of Athens in 431-429 B. C. (at present interpreted as typhus, the epidemics in the Roman Republic of the V and IV centuries B. C., and epidemics suffered by the Roman Empire (especially the plague of the Antonines in the Second century, and that of Cyprian in the Third century. Which are interpreted as smallpox and measles. Finally, we expose data of the plague suffered by Byzantine in time of Emperor Justinian, which is now undoubtedly the main scourge of bubonic plague.

  5. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    OpenAIRE

    Richard, Vincent; Riehm, Julia M.; Herindrainy, Perlinot; Soanandrasana , Rahelinirina; Ratsitoharina, Maherisoa; Rakotomanana, Fanjasoa; Andrianalimanana, Samuel; Scholz, Holger C; Rajerison, Minoarisoa

    2015-01-01

    International audience; Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period , 17 suspected, 2 presumptive, and 3 confirmed human cases were identified,and all 15 of untreated patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat sa...

  6. Plague dynamics are driven by climate variation

    DEFF Research Database (Denmark)

    Stenseth, Nils Chr.; Samia, Noelle I.; Viljugrein, Hildegunn

    2006-01-01

    prevalence in gerbils increases with warmer springs and wetter summers: A 1°C increase in spring is predicted to lead to a >50% increase in prevalence. Climatic conditions favoring plague apparently existed in this region at the onset of the Black Death as well as when the most recent plague pandemic arose...

  7. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015

    OpenAIRE

    Ramasindrazana, Beza; Andrianaivoarimanana, Voahangy; Rakotondramanga, Jean Marius; Birdsell, Dawn N.; Ratsitorahina, Maherisoa; Rajerison, Minoarisoa

    2017-01-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number?1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.

  8. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015.

    Science.gov (United States)

    Ramasindrazana, Beza; Andrianaivoarimanana, Voahangy; Rakotondramanga, Jean Marius; Birdsell, Dawn N; Ratsitorahina, Maherisoa; Rajerison, Minoarisoa

    2017-03-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.

  9. Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

    Science.gov (United States)

    McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick

    2011-01-01

    Background Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. Methods and Results Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD50) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. Conclusion Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen. PMID:21347450

  10. Levofloxacin cures experimental pneumonic plague in African green monkeys.

    Directory of Open Access Journals (Sweden)

    Robert Colby Layton

    Full Text Available BACKGROUND: Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. METHODS AND RESULTS: Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops were challenged via head-only aerosol inhalation with 3-145 (mean = 65 50% lethal (LD(50 doses of Y. pestis strain CO92. Telemetered body temperature >39 °C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a "humanized" dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53-165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. CONCLUSION: Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.

  11. [Resurgence of the plague in the Ikongo district of Madagascar in 1998. 1. Epidemiological aspects in the human population].

    Science.gov (United States)

    Migliani, R; Ratsitorahina, M; Rahalison, L; Rakotoarivony, I; Duchemin, J B; Duplantier, J M; Rakotonomenjanahary, J; Chanteau, S

    2001-05-01

    Between the 20th October and the 18th November 1998, an outbreak of bubonic plague was declared in a hamlet in the Ikongo district of Madagascar. We conducted an epidemiological survey because of the re-emergence of the disease in this area (the last cases had been notified in 1965) and because of the low altitude compared to the classical Malagasy foci. The outbreak had been preceded by an important rat epizootics during September. A total of 21 cases were registered with an attack rate of 16.7% (21/126) and a lethality rate of 33% (7/21). The disease was more prevalent in males (66% of cases) and children aged < 15 years, as observed in general throughout the country. The anti-F1 seroprevalence among the contact population was 13.5% (13/96), probably attributable to subclinical infection by Yersinia pestis. No rodent was trapped during the survey, but an endemic hedgehog (Tenrec ecaudatus) was highly seropositive, suggesting a recent transmission of the plague bacillus among this species. The small mammals and vectors possibly involved in these new foci were investigated in May 1999.

  12. Plague

    Science.gov (United States)

    ... Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS Division of ...

  13. Yersinia pestis requires the 2-component regulatory system OmpR-EnvZ to resist innate immunity during the early and late stages of plague.

    Science.gov (United States)

    Reboul, Angéline; Lemaître, Nadine; Titecat, Marie; Merchez, Maud; Deloison, Gaspard; Ricard, Isabelle; Pradel, Elizabeth; Marceau, Michaël; Sebbane, Florent

    2014-11-01

    Plague is transmitted by fleas or contaminated aerosols. To successfully produce disease, the causal agent (Yersinia pestis) must rapidly sense and respond to rapid variations in its environment. Here, we investigated the role of 2-component regulatory systems (2CSs) in plague because the latter are known to be key players in bacterial adaptation to environmental change. Along with the previously studied PhoP-PhoQ system, OmpR-EnvZ was the only one of Y. pestis' 23 other 2CSs required for production of bubonic, septicemic, and pneumonic plague. In vitro, OmpR-EnvZ was needed to counter serum complement and leukocytes but was not required for the secretion of antiphagocyte exotoxins. In vivo, Y. pestis lacking OmpR-EnvZ did not induce an early immune response in the skin and was fully virulent in neutropenic mice. We conclude that, throughout the course of Y. pestis infection, OmpR-EnvZ is required to counter toxic effectors secreted by polymorphonuclear leukocytes in the tissues. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. The trophic responses of two different rodent–vector–plague systems to climate change

    Science.gov (United States)

    Xu, Lei; Schmid, Boris V.; Liu, Jun; Si, Xiaoyan; Stenseth, Nils Chr.; Zhang, Zhibin

    2015-01-01

    Plague, the causative agent of three devastating pandemics in history, is currently a re-emerging disease, probably due to climate change and other anthropogenic changes. Without understanding the response of plague systems to anthropogenic or climate changes in their trophic web, it is unfeasible to effectively predict years with high risks of plague outbreak, hampering our ability for effective prevention and control of the disease. Here, by using surveillance data, we apply structural equation modelling to reveal the drivers of plague prevalence in two very different rodent systems: those of the solitary Daurian ground squirrel and the social Mongolian gerbil. We show that plague prevalence in the Daurian ground squirrel is not detectably related to its trophic web, and that therefore surveillance efforts should focus on detecting plague directly in this ecosystem. On the other hand, plague in the Mongolian gerbil is strongly embedded in a complex, yet understandable trophic web of climate, vegetation, and rodent and flea densities, making the ecosystem suitable for more sophisticated low-cost surveillance practices, such as remote sensing. As for the trophic webs of the two rodent species, we find that increased vegetation is positively associated with higher temperatures and precipitation for both ecosystems. We furthermore find a positive association between vegetation and ground squirrel density, yet a negative association between vegetation and gerbil density. Our study thus shows how past surveillance records can be used to design and improve existing plague prevention and control measures, by tailoring them to individual plague foci. Such measures are indeed highly needed under present conditions with prevailing climate change. PMID:25540277

  15. The trophic responses of two different rodent-vector-plague systems to climate change.

    Science.gov (United States)

    Xu, Lei; Schmid, Boris V; Liu, Jun; Si, Xiaoyan; Stenseth, Nils Chr; Zhang, Zhibin

    2015-02-07

    Plague, the causative agent of three devastating pandemics in history, is currently a re-emerging disease, probably due to climate change and other anthropogenic changes. Without understanding the response of plague systems to anthropogenic or climate changes in their trophic web, it is unfeasible to effectively predict years with high risks of plague outbreak, hampering our ability for effective prevention and control of the disease. Here, by using surveillance data, we apply structural equation modelling to reveal the drivers of plague prevalence in two very different rodent systems: those of the solitary Daurian ground squirrel and the social Mongolian gerbil. We show that plague prevalence in the Daurian ground squirrel is not detectably related to its trophic web, and that therefore surveillance efforts should focus on detecting plague directly in this ecosystem. On the other hand, plague in the Mongolian gerbil is strongly embedded in a complex, yet understandable trophic web of climate, vegetation, and rodent and flea densities, making the ecosystem suitable for more sophisticated low-cost surveillance practices, such as remote sensing. As for the trophic webs of the two rodent species, we find that increased vegetation is positively associated with higher temperatures and precipitation for both ecosystems. We furthermore find a positive association between vegetation and ground squirrel density, yet a negative association between vegetation and gerbil density. Our study thus shows how past surveillance records can be used to design and improve existing plague prevention and control measures, by tailoring them to individual plague foci. Such measures are indeed highly needed under present conditions with prevailing climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  16. Reflections on the white plague.

    Science.gov (United States)

    Zumla, Alimuddin; Mwaba, Peter; Huggett, Jim; Kapata, Nathan; Chanda, Duncan; Grange, John

    2009-03-01

    Tuberculosis continues to be one of the leading causes of morbidity and mortality from infectious disease worldwide. When WHO declared tuberculosis a global emergency in 1993, the initial response from the international community was sluggish and inadequate. A resurgence of the disease, the emergence of multidrug-resistant and extensively drug-resistant strains, and the detrimental effect of the concurrent tuberculosis and HIV/AIDS epidemics on national control programmes in sub-Saharan Africa have all occurred despite the availability of effective combination treatment regimens. On the positive side, funding agencies and donor governments are at long last taking a serious interest in investing in tuberculosis research priorities defined by the Stop TB Partnership. Although this investment introduces optimism for eventual control of the White Plague, past failures remind us not to be complacent.

  17. A review of plague persistence with special emphasis on fleas

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E.

    2009-01-01

    Sylvatic plague is highly prevalent during infrequent epizootics that ravage the landscape of western North America. During these periods, plague dissemination is very efficient. Epizootics end when rodent and flea populations are decimated and vectored transmission declines. A second phase (enzootic plague) ensues when plague is difficult to detect from fleas, hosts or the environment, and presents less of a threat to public health.

  18. Plague, a reemerging disease in Madagascar.

    Science.gov (United States)

    Chanteau, S; Ratsifasoamanana, L; Rasoamanana, B; Rahalison, L; Randriambelosoa, J; Roux, J; Rabeson, D

    1998-01-01

    Human cases of plague, which had virtually disappeared in Madagascar after the 1930s, reappeared in 1990 with more than 200 confirmed or presumptive cases reported each year since. In the port of Mahajanga, plague has been reintroduced, and epidemics occur every year. In Antananarivo, the capital, the number of new cases has increased, and many rodents are infected with Yersinia pestis. Despite surveillance for the sensitivity of Y. pestis and fleas to drugs and insecticides and control measures to prevent the spread of sporadic cases, the elimination of plague has been difficult because the host and reservoir of the bacillus, Rattus rattus, is both a domestic and a sylvatic rat.

  19. Sylvatic plague vaccine: combating plague in prarie dogs and black-footed ferrets

    Science.gov (United States)

    Rocke, Tonie E.; Abbott, Rachel C.

    2012-01-01

    After achieving promising results in laboratory trials, researchers at the USGS National Wildlife Health Center (NWHC) and University of Wisconsin at Madison will soon begin field testing a new oral vaccine for sylvatic plague, a devastating disease affecting prairie dogs and other mammals, particularly the endangered black-footed ferret. Our team has developed and is currently registering a sylvatic plague vaccine (SPV) that uses raccoon poxvirus (RCN) to express two key antigens of the Yersinia pestis bacterium, the causative agent of plague.

  20. A Decade of Plague in Mahajanga, Madagascar: Insights into the Global Maritime Spread of Pandemic Plague

    OpenAIRE

    Vogler, Amy J; Chan, Fabien; Nottingham, Roxanne; Andersen, Genevieve; Drees, Kevin; Beckstrom-Sternberg, Stephen M.; David M Wagner; Chanteau, Suzanne; Keim, Paul

    2013-01-01

    ABSTRACT A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62?years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (S...

  1. Climate-driven spatial dynamics of plague among prairie dog colonies.

    Science.gov (United States)

    Snäll, T; O'Hara, R B; Ray, C; Collinge, S K

    2008-02-01

    We present a Bayesian hierarchical model for the joint spatial dynamics of a host-parasite system. The model was fitted to long-term data on regional plague dynamics and metapopulation dynamics of the black-tailed prairie dog, a declining keystone species of North American prairies. The rate of plague transmission between colonies increases with increasing precipitation, while the rate of infection from unknown sources decreases in response to hot weather. The mean annual dispersal distance of plague is about 10 km, and topographic relief reduces the transmission rate. Larger colonies are more likely to become infected, but colony area does not affect the infectiousness of colonies. The results suggest that prairie dog movements do not drive the spread of plague through the landscape. Instead, prairie dogs are useful sentinels of plague epizootics. Simulations suggest that this model can be used for predicting long-term colony and plague dynamics as well as for identifying which colonies are most likely to become infected in a specific year.

  2. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    Science.gov (United States)

    Richard, Vincent; Herindrainy, Perlinot; Soanandrasana, Rahelinirina; Ratsitoharina, Maherisoa; Rakotomanana, Fanjasoa; Andrianalimanana, Samuel; Scholz, Holger C.; Rajerison, Minoarisoa

    2015-01-01

    Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies. PMID:25530466

  3. Lower Back Injuries Plague Many Athletes

    Science.gov (United States)

    ... fullstory_167201.html Lower Back Injuries Plague Many Athletes Surgery should be a last resort for 3 ... News) -- Back injuries are common, especially among competitive athletes. Nearly 1 in 3 athletes playing professional or ...

  4. Pneumonic plague outbreak, Northern Madagascar, 2011.

    Science.gov (United States)

    Richard, Vincent; Riehm, Julia M; Herindrainy, Perlinot; Soanandrasana, Rahelinirina; Ratsitoharina, Maherisoa; Rakotomanana, Fanjasoa; Andrianalimanana, Samuel; Scholz, Holger C; Rajerison, Minoarisoa

    2015-01-01

    Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies.

  5. Secondhand Smoke Still Plagues Some Cancer Survivors

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166834.html Secondhand Smoke Still Plagues Some Cancer Survivors Study found they ... number of nonsmoking cancer survivors exposed to secondhand smoke is down significantly in the United States, but ...

  6. [Epidemiological data on the plague in Madagascar].

    Science.gov (United States)

    Ratsitorahina, M; Chanteau, S; Rosso, M L; Randriambelosoa, J; Ratsifasoamanana, L; Rabarijaona, L P; Mauclère, P; Migliani, R

    2002-01-01

    The first case of plague was introduced in Madagascar in 1898 in the east coast by way of boat from India. In 1921, plague reach the highlands and a large epidemic over the next twenty years. Until the beginning of the 80's, only of few case were identified, notified mostly in rural setting. However gradually it has re-emerged as a public health problem. Urban plague is located in the city of Antananarivo (resurgence in 1978 after 28 years of apparent silence) and in Mahajanga port (resurgence in 1991 after 63 years of silence). The reactivation of the Plague National Control Program from 1994 will allow better surveillance. The aim of this analysis is to update the epidemiological data on human plague in Madagascar based on reported cases obtained from the Central Lab of the Pasteur Institute of Madagascar from 1980 to 2001 (16,928 suspected cases of which 3,500 are likely positives or confirmed positives). The Plague season runs from October to March on the central highlands and July to November on the north-western coast. Sex-ratio male/female is 1.3/1, and the age-group of 5 to 25 years is more affected. The case fatality rate was 40% in the beginning of the 1980's, and decreased to 20% by the end of the 1990's. The percentage of case with pulmonary plague decrease from 15% to less than 5%. However, geographical extension is demonstrated: 4 districts in 1980, 30 districts in 1999 and 21 districts in 2001. In 2002, the diffusion of a new rapid test (reagent strip) in the primary health centres (CSB) in 42 endemic districts may help to decrease the morbidity and the letality due to plague and improve its control at the national level.

  7. Plague, a reemerging disease in Madagascar.

    OpenAIRE

    Chanteau, S; Ratsifasoamanana, L.; Rasoamanana, B.; Rahalison, L.; Randriambelosoa, J.; Roux, J.; Rabeson, D.

    1998-01-01

    Human cases of plague, which had virtually disappeared in Madagascar after the 1930s, reappeared in 1990 with more than 200 confirmed or presumptive cases reported each year since. In the port of Mahajanga, plague has been reintroduced, and epidemics occur every year. In Antananarivo, the capital, the number of new cases has increased, and many rodents are infected with Yersinia pestis. Despite surveillance for the sensitivity of Y. pestis and fleas to drugs and insecticides and control measu...

  8. Identification of risk factors for plague in the West Nile Region of Uganda.

    Science.gov (United States)

    Eisen, Rebecca J; MacMillan, Katherine; Atiku, Linda A; Mpanga, Joseph T; Zielinski-Gutierrez, Emily; Graham, Christine B; Boegler, Karen A; Enscore, Russell E; Gage, Kenneth L

    2014-06-01

    Plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused by Yersinia pestis. We sought to identify risk factors for plague by comparing villages with and without a history of human plague cases within a model-defined plague focus in the West Nile Region of Uganda. Although rat (Rattus rattus) abundance was similar inside huts within case and control villages, contact rates between rats and humans (as measured by reported rat bites) and host-seeking flea loads were higher in case villages. In addition, compared with persons in control villages, persons in case villages more often reported sleeping on reed or straw mats, storing food in huts where persons sleep, owning dogs and allowing them into huts where persons sleep, storing garbage inside or near huts, and cooking in huts where persons sleep. Compared with persons in case villages, persons in control villages more commonly reported replacing thatch roofing, and growing coffee, tomatoes, onions, and melons in agricultural plots adjacent to their homesteads. Rodent and flea control practices, knowledge of plague, distance to clinics, and most care-seeking practices were similar between persons in case villages and persons in control villages. Our findings reinforce existing plague prevention recommendations and point to potentially advantageous local interventions. © The American Society of Tropical Medicine and Hygiene.

  9. Navigable rivers facilitated the spread and recurrence of plague in pre-industrial Europe

    Science.gov (United States)

    Pak Hong, Y. R.

    2016-12-01

    nfectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatio-temporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347-1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river. This association remained robust in different regression model specifications. An increase of 100m in the width of river and a shortening of 1km distance between city and river resulted in 9 and 0.96 more plague outbreaks in our study period, respectively. We suggested that trade and transportation brought by river was an important medium for the spread and recurrence of plague in pre-industrial Europe.

  10. Identification of Risk Factors for Plague in the West Nile Region of Uganda

    Science.gov (United States)

    Eisen, Rebecca J.; MacMillan, Katherine; Atiku, Linda A.; Mpanga, Joseph T.; Zielinski-Gutierrez, Emily; Graham, Christine B.; Boegler, Karen A.; Enscore, Russell E.; Gage, Kenneth L.

    2014-01-01

    Plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused by Yersinia pestis. We sought to identify risk factors for plague by comparing villages with and without a history of human plague cases within a model-defined plague focus in the West Nile Region of Uganda. Although rat (Rattus rattus) abundance was similar inside huts within case and control villages, contact rates between rats and humans (as measured by reported rat bites) and host-seeking flea loads were higher in case villages. In addition, compared with persons in control villages, persons in case villages more often reported sleeping on reed or straw mats, storing food in huts where persons sleep, owning dogs and allowing them into huts where persons sleep, storing garbage inside or near huts, and cooking in huts where persons sleep. Compared with persons in case villages, persons in control villages more commonly reported replacing thatch roofing, and growing coffee, tomatoes, onions, and melons in agricultural plots adjacent to their homesteads. Rodent and flea control practices, knowledge of plague, distance to clinics, and most care-seeking practices were similar between persons in case villages and persons in control villages. Our findings reinforce existing plague prevention recommendations and point to potentially advantageous local interventions. PMID:24686743

  11. Colorado animal-based plague surveillance systems: relationships between targeted animal species and prediction efficacy of areas at risk for humans.

    Science.gov (United States)

    Lowell, Jennifer L; Eisen, Rebecca J; Schotthoefer, Anna M; Xiaocheng, Liang; Montenieri, John A; Tanda, Dale; Pape, John; Schriefer, Martin E; Antolin, Michael F; Gage, Kenneth L

    2009-06-01

    Human plague risks (Yersinia pestis infection) are greatest when epizootics cause high mortality among this bacterium's natural rodent hosts. Therefore, health departments in plague-endemic areas commonly establish animal-based surveillance programs to monitor Y. pestis infection among plague hosts and vectors. The primary objectives of our study were to determine whether passive animal-based plague surveillance samples collected in Colorado from 1991 to 2005 were sampled from high human plague risk areas and whether these samples provided information useful for predicting human plague case locations. By comparing locations of plague-positive animal samples with a previously constructed GIS-based plague risk model, we determined that the majority of plague-positive Gunnison's prairie dogs (100%) and non-prairie dog sciurids (85.82%), and moderately high percentages of sigmodontine rodents (71.4%), domestic cats (69.3%), coyotes (62.9%), and domestic dogs (62.5%) were recovered within 1 km of the nearest area posing high peridomestic risk to humans. In contrast, the majority of white-tailed prairie dog (66.7%), leporid (cottontailed and jack rabbits) (71.4%), and black-tailed prairie dog (93.0%) samples originated more than 1 km from the nearest human risk habitat. Plague-positive animals or their fleas were rarely (one of 19 cases) collected within 2 km of a case exposure site during the 24 months preceding the dates of illness onset for these cases. Low spatial accuracy for identifying epizootic activity prior to human plague cases suggested that other mammalian species or their fleas are likely more important sources of human infection in high plague risk areas. To address this issue, epidemiological observations and multi-locus variable number tandem repeat analyses (MLVA) were used to preliminarily identify chipmunks as an under-sampled, but potentially important, species for human plague risk in Colorado.

  12. A decade of plague in Mahajanga, Madagascar: insights into the global maritime spread of pandemic plague.

    Science.gov (United States)

    Vogler, Amy J; Chan, Fabien; Nottingham, Roxanne; Andersen, Genevieve; Drees, Kevin; Beckstrom-Sternberg, Stephen M; Wagner, David M; Chanteau, Suzanne; Keim, Paul

    2013-02-12

    A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates. Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions. The ultimate extinction of plague pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments. Maritime spread of plague led to the global dissemination of this disease and affected the course of human history. Multiple historical plague waves

  13. Burrowing Owls, Pulex irritans, and Plague.

    Science.gov (United States)

    Belthoff, James R; Bernhardt, Scott A; Ball, Christopher L; Gregg, Michael; Johnson, David H; Ketterling, Rachel; Price, Emily; Tinker, Juliette K

    2015-09-01

    Western Burrowing Owls (Athene cunicularia hypugaea) are small, ground-dwelling owls of western North America that frequent prairie dog (Cynomys spp.) towns and other grasslands. Because they rely on rodent prey and occupy burrows once or concurrently inhabited by fossorial mammals, the owls often harbor fleas. We examined the potential role of fleas found on burrowing owls in plague dynamics by evaluating prevalence of Yersinia pestis in fleas collected from burrowing owls and in owl blood. During 2012-2013, fleas and blood were collected from burrowing owls in portions of five states with endemic plague-Idaho, Oregon, Washington, Colorado, and South Dakota. Fleas were enumerated, taxonomically identified, pooled by nest, and assayed for Y. pestis using culturing and molecular (PCR) approaches. Owl blood underwent serological analysis for plague antibodies and nested PCR for detection of Y. pestis. Of more than 4750 fleas collected from owls, Pulex irritans, a known plague vector in portions of its range, comprised more than 99.4%. However, diagnostic tests for Y. pestis of flea pools (culturing and PCR) and owl blood (PCR and serology) were negative. Thus, even though fleas were prevalent on burrowing owls and the potential for a relationship with burrowing owls as a phoretic host of infected fleas exists, we found no evidence of Y. pestis in sampled fleas or in owls that harbored them. We suggest that studies similar to those reported here during plague epizootics will be especially useful for confirming these results.

  14. [Seroepidemiologic study of human plague in Madagascar].

    Science.gov (United States)

    Leroy, F

    1997-01-01

    An IgG anti-F1 Enzyme linked immunosorbent assay (Elisa) has been developed for plague diagnosis in the Malagasy republic. The sensitivity of the test was 91.4% and the specificity 98.5%. This technique is cheap and the cross reaction with other infections diseases prevalent in Madagascar is very limited. During the urban plague outbreak (Mahajanga city, 1995), the positive predictive value and the negative predictive value were 95.2% and 97% respectively. During this outbreak, the usefulness of the Elisa test for retrospective individual serodiagnosis was confirmed. Furthermore, the test confirmed plague among suspect patients without bacteriological diagnosis. The test was used for a sero-epidemiological study. Eight villages in the endemic area were investigated and 900 persons were studied. The overall seroprevalence was 6 times the officially prevalence of plague, notified at the Central Plague Laboratory. A large disparity of the seroprevalence was observed in the endemic area, with variation from < 1.5% to 15.5%. A high incidence of asymptomatic infections due to Yersinia pestis was found.

  15. Evaluation of Yersinia pestis transmission pathways for sylvatic plague in prairie dog populations in the western U.S.

    Science.gov (United States)

    Richgels, Katherine L. D.; Russell, Robin E.; Bron, Gebbiena; Rocke, Tonie E.

    2016-01-01

    Sylvatic plague, caused by the bacterium Yersinia pestis, is periodically responsible for large die-offs in rodent populations that can spillover and cause human mortalities. In the western US, prairie dog populations experience nearly 100% mortality during plague outbreaks, suggesting that multiple transmission pathways combine to amplify plague dynamics. Several alternate pathways in addition to flea vectors have been proposed, such as transmission via direct contact with bodily fluids or inhalation of infectious droplets, consumption of carcasses, and environmental sources of plague bacteria, such as contaminated soil. However, evidence supporting the ability of these proposed alternate pathways to trigger large-scale epizootics remains elusive. Here we present a short review of potential plague transmission pathways and use an ordinary differential equation model to assess the contribution of each pathway to resulting plague dynamics in black-tailed prairie dogs (Cynomys ludovicianus) and their fleas (Oropsylla hirsuta). Using our model, we found little evidence to suggest that soil contamination was capable of producing plague epizootics in prairie dogs. However, in the absence of flea transmission, direct transmission, i.e., contact with bodily fluids or inhalation of infectious droplets, could produce enzootic dynamics, and transmission via contact with or consumption of carcasses could produce epizootics. This suggests that these pathways warrant further investigation.

  16. Impact of the plague in Ancient Greece.

    Science.gov (United States)

    Soupios, M A

    2004-03-01

    Disease as a pivotal factor in determining the course of human events may be one og the least considered historical variables. When assessing the critical junctures of history, historians seem more inclined to focus on the impact of conquering armies, economic revolutions, and technologic breakthroughs. This analysis attempts to illustrate the seminal effects of the great plague of Athens. By depleting Athenian military personnel, depriving Athens of its charismatic leadership, and dissolving the system of ideals and principles that distinguished Athens from the rest of antiquity, the plague materially altered the outcome of the Peloponnesian War, which in turn deflected the flow of all subsequent Hellenic history.

  17. Successful Treatment of Human Plague with Oral Ciprofloxacin.

    Science.gov (United States)

    Apangu, Titus; Griffith, Kevin; Abaru, Janet; Candini, Gordian; Apio, Harriet; Okoth, Felix; Okello, Robert; Kaggwa, John; Acayo, Sarah; Ezama, Geoffrey; Yockey, Brook; Sexton, Christopher; Schriefer, Martin; Mbidde, Edward Katongole; Mead, Paul

    2017-03-01

    The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.

  18. Wild felids as hosts for human plague, Western United States

    Science.gov (United States)

    Bevins, S.N.; Tracey, J.A.; Franklin, S.P.; Schmit, V.L.; MacMillan, M.L.; Gage, K.L.; Schriefer, M.E.; Logan, K.A.; Sweanor, L.L.; Alldredge, M.W.; Krumm, C.; Boyce, W.M.; Vickers, W.; Riley, S.P.D.; Lyren, L.M.; Boydston, E.E.; Fisher, R.N.; Roelke, M.E.; Salman, M.; Crooks, K.R.; VandeWoude, S.

    2009-01-01

    Plague seroprevalence was estimated in populations pumas and bobcats in the western United States. High levels of exposure in plague-endemic regions indicate the need to consider the ecology and pathobiology of plague nondomestic felid hosts to better understand the role of these species in disease persistence and transmission.

  19. Influence of human activity patterns on epidemiology of plague in ...

    African Journals Online (AJOL)

    Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs ...

  20. [The plague and the art of painting: some examples].

    Science.gov (United States)

    Dequeker, J

    1999-01-01

    The author gives four examples of pictures representing the plague: "The Plague of Asdod" by Nicolas Poussin, a picture of Saint Roch by the Master of Frankfort, "Saint Roch Interceding for the Plague-stricken" by Peter Paul Rubens and "The Sisters of Saint Elisabeth Hospital in Antwerp and the Works of Mercy" by Jacob Jordaens.

  1. Landscape and Residential Variables Associated with Plague-Endemic Villages in the West Nile Region of Uganda

    Science.gov (United States)

    MacMillan, Katherine; Enscore, Russell E.; Ogen-Odoi, Asaph; Borchert, Jeff N.; Babi, Nackson; Amatre, Gerald; Atiku, Linda A.; Mead, Paul S.; Gage, Kenneth L.; Eisen, Rebecca J.

    2011-01-01

    Plague, caused by the bacteria Yersinia pestis, is a severe, often fatal disease. This study focuses on the plague-endemic West Nile region of Uganda, where limited information is available regarding environmental and behavioral risk factors associated with plague infection. We conducted observational surveys of 10 randomly selected huts within historically classified case and control villages (four each) two times during the dry season of 2006 (N = 78 case huts and N = 80 control huts), which immediately preceded a large plague outbreak. By coupling a previously published landscape-level statistical model of plague risk with this observational survey, we were able to identify potential residence-based risk factors for plague associated with huts within historic case or control villages (e.g., distance to neighboring homestead and presence of pigs near the home) and huts within areas previously predicted as elevated risk or low risk (e.g., corn and other annual crops grown near the home, water storage in the home, and processed commercial foods stored in the home). The identified variables are consistent with current ecologic theories on plague transmission dynamics. This preliminary study serves as a foundation for future case control studies in the area. PMID:21363983

  2. Epidemiological analysis of the Eyam plague outbreak of 1665–1666

    Science.gov (United States)

    Whittles, Lilith K.

    2016-01-01

    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. PMID:27170724

  3. Epidemiological analysis of the Eyam plague outbreak of 1665-1666.

    Science.gov (United States)

    Whittles, Lilith K; Didelot, Xavier

    2016-05-11

    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. © 2016 The Authors.

  4. Saving Resources with Plagues in Genetic Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    de Vega, F F; Cantu-Paz, E; Lopez, J I; Manzano, T

    2004-06-15

    The population size of genetic algorithms (GAs) affects the quality of the solutions and the time required to find them. While progress has been made in estimating the population sizes required to reach a desired solution quality for certain problems, in practice the sizing of populations is still usually performed by trial and error. These trials might lead to find a population that is large enough to reach a satisfactory solution, but there may still be opportunities to optimize the computational cost by reducing the size of the population. This paper presents a technique called plague that periodically removes a number of individuals from the population as the GA executes. Recently, the usefulness of the plague has been demonstrated for genetic programming. The objective of this paper is to extend the study of plagues to genetic algorithms. We experiment with deceptive trap functions, a tunable difficult problem for GAs, and the experiments show that plagues can save computational time while maintaining solution quality and reliability.

  5. Plague metapopulation dynamics in a natural reservoir

    DEFF Research Database (Denmark)

    Davis, S; Klassovskiy, N; Ageyev, V

    2007-01-01

    The ecology of plague (Yersinia pestis infection) in its ancient foci in Central Asia remains poorly understood. We present field data from two sites in Kazakhstan where the great gerbil (Rhombomys opimus) is the major natural host. Family groups inhabit and defend burrow systems spaced throughout...

  6. Resistance to plague among black-tailed prairie dog populations.

    Science.gov (United States)

    Rocke, Tonie E; Williamson, Judy; Cobble, Kacy R; Busch, Joseph D; Antolin, Michael F; Wagner, David M

    2012-02-01

    In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (pplague resistance.

  7. A High-Coverage Yersinia pestis Genome from a Sixth-Century Justinianic Plague Victim.

    Science.gov (United States)

    Feldman, Michal; Harbeck, Michaela; Keller, Marcel; Spyrou, Maria A; Rott, Andreas; Trautmann, Bernd; Scholz, Holger C; Päffgen, Bernd; Peters, Joris; McCormick, Michael; Bos, Kirsten; Herbig, Alexander; Krause, Johannes

    2016-11-01

    The Justinianic Plague, which started in the sixth century and lasted to the mid eighth century, is thought to be the first of three historically documented plague pandemics causing massive casualties. Historical accounts and molecular data suggest the bacterium Yersinia pestis as its etiological agent. Here we present a new high-coverage (17.9-fold) Y. pestis genome obtained from a sixth-century skeleton recovered from a southern German burial site close to Munich. The reconstructed genome enabled the detection of 30 unique substitutions as well as structural differences that have not been previously described. We report indels affecting a lacl family transcription regulator gene as well as nonsynonymous substitutions in the nrdE, fadJ, and pcp genes, that have been suggested as plague virulence determinants or have been shown to be upregulated in different models of plague infection. In addition, we identify 19 false positive substitutions in a previously published lower-coverage Y. pestis genome from another archaeological site of the same time period and geographical region that is otherwise genetically identical to the high-coverage genome sequence reported here, suggesting low-genetic diversity of the plague during the sixth century in rural southern Germany. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Patterns of Human Plague in Uganda, 2008-2016.

    Science.gov (United States)

    Forrester, Joseph D; Apangu, Titus; Griffith, Kevin; Acayo, Sarah; Yockey, Brook; Kaggwa, John; Kugeler, Kiersten J; Schriefer, Martin; Sexton, Christopher; Ben Beard, C; Candini, Gordian; Abaru, Janet; Candia, Bosco; Okoth, Jimmy Felix; Apio, Harriet; Nolex, Lawrence; Ezama, Geoffrey; Okello, Robert; Atiku, Linda; Mpanga, Joseph; Mead, Paul S

    2017-09-01

    Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008-2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague. Reports of an unusual number of dead rats in a patient's village around the time of illness onset was significantly associated with laboratory confirmation of plague. This descriptive summary of human plague in Uganda highlights the episodic nature of the disease, as well as the potential that, even in endemic areas, illnesses of other etiologies might be being mistaken for plague.

  9. Patterns of Human Plague in Uganda, 2008–2016

    Science.gov (United States)

    Forrester, Joseph D.; Apangu, Titus; Griffith, Kevin; Acayo, Sarah; Yockey, Brook; Kaggwa, John; Kugeler, Kiersten J.; Schriefer, Martin; Sexton, Christopher; Ben Beard, C.; Candini, Gordian; Abaru, Janet; Candia, Bosco; Okoth, Jimmy Felix; Apio, Harriet; Nolex, Lawrence; Ezama, Geoffrey; Okello, Robert; Atiku, Linda; Mpanga, Joseph

    2017-01-01

    Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008–2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague. Reports of an unusual number of dead rats in a patient’s village around the time of illness onset was significantly associated with laboratory confirmation of plague. This descriptive summary of human plague in Uganda highlights the episodic nature of the disease, as well as the potential that, even in endemic areas, illnesses of other etiologies might be being mistaken for plague. PMID:28820134

  10. Pneumonic Plague: The Darker Side of Yersinia pestis.

    Science.gov (United States)

    Pechous, Roger D; Sivaraman, Vijay; Stasulli, Nikolas M; Goldman, William E

    2016-03-01

    Inhalation of the bacterium Yersinia pestis results in primary pneumonic plague. Pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. Its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of Y. pestis as a biological weapon. Importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of Y. pestis infections. In this review we describe the characteristics of pneumonic plague, focusing on its disease progression and pathogenesis. The rapid time-course, severity, and difficulty of treating pneumonic plague highlight how differences in the route of disease transmission can enhance the lethality of an already deadly pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. [Study on the spatial and temporal distribution of animal plague in Junggar Basin plague focus].

    Science.gov (United States)

    Guo, Rong; Dai, Xiang; Cao, Hanli; Xia, Lianxu; Abuli, Miti; Abuli, Kemu; Wang, Xinhui; Aza, Ti; Jiang, Wei; Li, Bing; Zhang, Xiaobing; Lei, Gang; Wang, Qiguo; Luo, Tao; Meng, Weiwei; Buren, Mingde; Re, Na; Chen, Yan; Zhang, Yujiang

    2014-02-01

    To explore the spatial and temporal distributions of animal plague in Junggar Basin natural plague focus. Data regarding plague antibody (F1) in serum of Great Gerbil (Rhombomys opimus, R. opimus) which were collected from 2005 to 2012 in Junggar Basin and analyzed. The changing rates on the positivity of F1 that appeared spatially and temporally were also analyzed. A total of 4 825 R. opimus serum samples were collected in 13 administrative regions in Junggar Basin. showed that plague R. opimus existed in two areas-Gurbantonggut desert in the eastern-center and the clay desert of western Junggar Basin. However, in these two areas, the intensity of animal plague prevalence was different. In the former region where Yesinia pestis positive serum was detected from R. opimus, the detected rate of R. opimus was 8.39%. However, in the latter areas, the average positive rate was 1.56%. The changing trends of R. opimus plague prevalence were also varied annually. In the western Junggar Basin, the trend showed a slowly downward profile. The serum positive rate of R. opimus for Yesinia pestis decreased, from 7.59% in 2005 to 0.61% in 2008, and appeared as a resting state that none of the positive sample could be found since then. However, in the eastern-center Junggar Basin area-also named as Gurbantonggut desert which had been divided into 3 segments(western, central and eastern, according to related geographical characteristics), the changing trends of animal plague seemed quite complex. In the western segment, the animal plague had two epidemic peaks-in 2006 and 2010, with the interval of 4 years, with the higher peak of all the three geographic segments as 45.65% in 2010 and the positive serum of R. opimus for plague could be detected each year from 2006 to 2012. However, there were 3 epidemic peaks in the same period in the central and eastern segments. In the central segment, the peaks appeared in 2006, 2009 and 2011, with the intervals as 2.5 years and the average

  12. Range-wide Determinants of Plague Distribution in North America

    Science.gov (United States)

    Maher, Sean P.; Ellis, Christine; Gage, Kenneth L.; Enscore, Russell E.; Peterson, A. Townsend

    2010-01-01

    Plague, caused by the bacterium Yersinia pestis, is established across western North America, and yet little is known of what determines the broad-scale dimensions of its overall range. We tested whether its North American distribution represents a composite of individual host–plague associations (the “Host Niche Hypothesis”), or whether mammal hosts become infected only at sites overlapping ecological conditions appropriate for plague transmission and maintenance (the “Plague Niche Hypothesis”). We took advantage of a novel data set summarizing plague records in wild mammals newly digitized from paper-based records at the Centers for Disease Control and Prevention to develop range-wide tests of ecological niche similarity between mammal host niches and plague-infected host niches. Results indicate that plague infections occur under circumstances distinct from the broader ecological distribution of hosts, and that plague-infected niches are similar among hosts; hence, evidence coincides with the predictions of the Plague Niche Hypothesis, and contrasts with those of the Host Niche Hypothesis. The “plague niche” is likely driven by ecological requirements of vector flea species. PMID:20889857

  13. Molecular insights into the history of plague.

    Science.gov (United States)

    Drancourt, Michel; Raoult, Didier

    2002-01-01

    Because of the limits inherent in historical sources on ancient plague epidemics, many questions concerning their etiology and epidemiology remain unanswered. Molecular biology tools and the use of dental pulp as a preserved source of bacterial DNA enabled us to demonstrate that Yersinia pestis was the etiologic agent of the 1347 European Black Death and of two additional epidemics in 1590 and 1722 in southern France.

  14. Field efficacy trials with sylvatic plague vaccine

    Science.gov (United States)

    Richgels, Katherine; Russell, Robin E.; Rocke, Tonie E.

    2017-01-01

    These data were collected as part of a field trial to test the efficacy of a sylvatic plague vaccine. Treatment and control sites were selected randomly from the available sites at each location. Site pairs were a minimum of 20 acres, (with a few exceptions). Prairie dog trapping took place a minimum of two weeks post-baiting and trapping procedures were approved by the NWHC Animal Care and Use Committee as well as individual states as required.

  15. Gr1(+) Cells Control Growth of YopM-Negative Yersinia pestis during Systemic Plague

    NARCIS (Netherlands)

    Ye, Z.; Kerschen, E.J.; Cohen, D.; Kaplan, A.M.; Rooijen, van N.; Straley, S.C.

    2009-01-01

    YopM, a protein toxin of Yersinia pestis, is necessary for virulence in a mouse model of systemic plague. We previously reported YopM-dependent natural killer (NK) cell depletion from blood and spleen samples of infected mice. However, in this study we found that infection with Y. pestis KIM5

  16. Disease limits populations: plague and black-tailed prairie dogs

    Science.gov (United States)

    Cully, Jack F.; Johnson, T.; Collinge, S.K.; Ray, C.

    2010-01-01

    Plague is an exotic vector-borne disease caused by the bacterium Yersinia pestis that causes mortality rates approaching 100% in black-tailed prairie dogs (Cynomys ludovicianus). We mapped the perimeter of the active portions of black-tailed prairie dog colonies annually between 1999 and 2005 at four prairie dog colony complexes in areas with a history of plague, as well as at two complexes that were located outside the distribution of plague at the time of mapping and had therefore never been affected by the disease. We hypothesized that the presence of plague would significantly reduce overall black-tailed prairie dog colony area, reduce the sizes of colonies on these landscapes, and increase nearest-neighbor distances between colonies. Within the region historically affected by plague, individual colonies were smaller, nearest-neighbor distances were greater, and the proportion of potential habitat occupied by active prairie dog colonies was smaller than at plague-free sites. Populations that endured plague were composed of fewer large colonies (>100 ha) than populations that were historically plague free. We suggest that these differences among sites in colony size and isolation may slow recolonization after extirpation. At the same time, greater intercolony distances may also reduce intercolony transmission of pathogens. Reduced transmission among smaller and more distant colonies may ultimately enhance long-term prairie dog population persistence in areas where plague is present.

  17. Disease limits populations: plague and black-tailed prairie dogs.

    Science.gov (United States)

    Cully, Jack F; Johnson, Tammi L; Collinge, Sharon K; Ray, Chris

    2010-01-01

    Plague is an exotic vector-borne disease caused by the bacterium Yersinia pestis that causes mortality rates approaching 100% in black-tailed prairie dogs (Cynomys ludovicianus). We mapped the perimeter of the active portions of black-tailed prairie dog colonies annually between 1999 and 2005 at four prairie dog colony complexes in areas with a history of plague, as well as at two complexes that were located outside the distribution of plague at the time of mapping and had therefore never been affected by the disease. We hypothesized that the presence of plague would significantly reduce overall black-tailed prairie dog colony area, reduce the sizes of colonies on these landscapes, and increase nearest-neighbor distances between colonies. Within the region historically affected by plague, individual colonies were smaller, nearest-neighbor distances were greater, and the proportion of potential habitat occupied by active prairie dog colonies was smaller than at plague-free sites. Populations that endured plague were composed of fewer large colonies (>100 ha) than populations that were historically plague free. We suggest that these differences among sites in colony size and isolation may slow recolonization after extirpation. At the same time, greater intercolony distances may also reduce intercolony transmission of pathogens. Reduced transmission among smaller and more distant colonies may ultimately enhance long-term prairie dog population persistence in areas where plague is present.

  18. Was Plague an Exclusively Urban Phenomenon? Plague Mortality in the Seventeenth-Century Low Countries

    NARCIS (Netherlands)

    Curtis, D.R.

    2016-01-01

    Current scholarship reinforces the notion that by the early modern period, plague had become largely an urban concern in northwestern Europe. However, a data set comprised of burial information from the seventeenth-century Low Countries suggests that plague’s impact on the countryside was far more

  19. [Monitoring the Microtus fuscus plague epidemic in Sichuan province during 2000 - 2008.

    DEFF Research Database (Denmark)

    Wang, Li-Mao; Song, Xiao-Yu; Zhu, Xiao-Ping

    2009-01-01

    OBJECTIVE: To analyze the epidemic tendency of Microtus fuscus plague during 2000 - 2008 in Sichuan province. METHODS: To investigate the plague each year according to "overall Plan of the Plague in the Whole Nation" and "Surveillance Program of Sichuan Province Plague". RESULTS: There were plague...... of fleas, Callopsylla sparsilis, Amphipsylla tutua tutua and Rhadinopsylla dahurica vicina, with the overall infection rate as 0.054%. CONCLUSION: Plague among Microtus fuscus showed a continuous epidemic in Sichuan province during 2000 - 2008....

  20. A review of plague persistence with special emphasis on fleas.

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E

    2009-06-01

    Sylvatic plague is highly prevalent during infrequent epizootics that ravage the landscape of western North America. During these periods, plague dissemination is very efficient. Epizootics end when rodent and flea populations are decimated and vectored transmission declines. A second phase (enzootic plague) ensues when plague is difficult to detect from fleas, hosts or the environment, and presents less of a threat to public health. Recently, researchers have hypothesized that the bacterium (Yersinia pestis) responsible for plague maintains a continuous state of high virulence and thus only changes in transmission efficiency explain the shift between alternating enzootic and epizootic phases. However, if virulent transmission becomes too inefficient, strong selection might favor an alternate survival strategy. Another plausible non-exclusive hypothesis, best supported from Asian field studies, is that Y. pestis persists (locally) at foci by maintaining a more benign relationship within adapted rodents during the long expanses of time between outbreaks. From this vantage, it can revert to the epizootic (transmission efficient) form. Similarly, in the United States (US), enzootic plague persistence has been proposed to develop sequestered within New World rodent carriers. However, the absence of clear support for rodent carriers in North America has encouraged a broader search for alternative explanations. A telluric plague existence has been proposed. However, the availability of flea life stages and their hosts could critically supplement environmental plague sources, or fleas might directly represent a lowlevel plague reservoir. Here, we note a potentially pivotal role for fleas. These epizootic plague vectors should be closely studied with newer more exacting methods to determine their potential to serve as participants in or accomplices to a plague persistence reservoir.

  1. Successful plague control in Namibia | Shangula | South African ...

    African Journals Online (AJOL)

    Objective. To demonstrate that plague can be successfully controlled. Design. A descriptive study outlining patterns of plague occurrence in relation to variables such as age group, gender, place and time. Setting. Two northern districts, namely Engela in Ohangwena region and Onandjokwe in Oshikoto region, an area of 2 ...

  2. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics.

    Science.gov (United States)

    Eisen, Rebecca J; Bearden, Scott W; Wilder, Aryn P; Montenieri, John A; Antolin, Michael F; Gage, Kenneth L

    2006-10-17

    Plague is a highly virulent disease believed to have killed millions during three historic human pandemics. Worldwide, it remains a threat to humans and is a potential agent of bioterrorism. Dissemination of Yersinia pestis, the etiological agent of plague, by blocked fleas has been the accepted paradigm for flea-borne transmission. However, this mechanism, which requires a lengthy extrinsic incubation period before a short infectious window often followed by death of the flea, cannot sufficiently explain the rapid rate of spread that typifies plague epidemics and epizootics. Inconsistencies between the expected rate of spread by blocked rat fleas and that observed during the Black Death has even caused speculation that plague was not the cause of this medieval pandemic. We used the primary vector to humans in North America, Oropsylla montana, which rarely becomes blocked, as a model for studying alternative flea-borne transmission mechanisms. Our data revealed that, in contrast to the classical blocked flea model, O. montana is immediately infectious, transmits efficiently for at least 4 d postinfection (early phase) and may remain infectious for a long time because the fleas do not suffer block-induced mortality. These factors match the criteria required to drive plague epizootics as defined by recently published mathematical models. The scenario of efficient early-phase transmission by unblocked fleas described in our study calls for a paradigm shift in concepts of how Y. pestis is transmitted during rapidly spreading epizootics and epidemics, including, perhaps, the Black Death.

  3. Nathaniel Hodges (1629-1688): Plague doctor.

    Science.gov (United States)

    Duffin, Christopher J

    2016-02-01

    Nathaniel Hodges was the son of Thomas Hodges (1605-1672), an influential Anglican preacher and reformer with strong connections in the political life of Carolingian London. Educated at Westminster School, Trinity College Cambridge and Christ Church College, Oxford, Nathaniel established himself as a physician in Walbrook Ward in the City of London. Prominent as one of a handful of medical men who remained in London during the time of the Great Plague of 1665, he wrote the definitive work on the outbreak. His daily precautions against contracting the disease included fortifying himself with Théodore de Mayerne's antipestilential electuary and the liberal consumption of Sack. Hodges' approach to the treatment of plague victims was empathetic and based on the traditional Galenic method rather than Paracelsianism although he was pragmatic in the rejection of formulae and simples which he judged from experience to be ineffective. Besieged by financial problems in later life, his practice began to fail in the 1680s and he eventually died in a debtor's prison. © The Author(s) 2014.

  4. A curve of thresholds governs plague epizootics in Central Asia

    DEFF Research Database (Denmark)

    Reijniers, Jonas; Davis, Stephen; Begon, Mike

    2012-01-01

    A core concept of infectious disease epidemiology is the abundance threshold, below which an infection is unable to invade or persist. There have been contrasting theoretical predictions regarding the nature of this threshold for vector-borne diseases, but for infections with an invertebrate vector......, it is common to assume a threshold defined by the ratio of vector and host abundances. Here, we show in contrast, both from field data and model simulations, that for plague (Yersinia pestis) in Kazakhstan, the invasion threshold quantity is based on the product of its host (Rhombomys opimus) and vector...... (mainly Xenopsylla spp.) abundances, resulting in a combined threshold curve with hyperbolic shape. This shape implies compensation between host and vector abundances in permitting infection, which has important implications for disease control. Realistic joint thresholds, supported by data, should...

  5. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    Science.gov (United States)

    Quenee, Lauriane E.; Hermanas, Timothy M.; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C.; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-01-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv−/−) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv−/− mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv−/− mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines. PMID:22896664

  6. Hong Kong Junk: Plague and the Economy of Chinese Things.

    Science.gov (United States)

    Peckham, Robert

    2016-01-01

    Histories of the Third Plague Pandemic, which diffused globally from China in the 1890s, have tended to focus on colonial efforts to regulate the movement of infected populations, on the state's draconian public health measures, and on the development of novel bacteriological theories of disease causation. In contrast, this article focuses on the plague epidemic in Hong Kong and examines colonial preoccupations with Chinese "things" as sources of likely contagion. In the 1890s, laboratory science invested plague with a new identity as an object to be collected, cultivated, and depicted in journals. At the same time, in the increasingly vociferous anti-opium discourse, opium was conceived as a contagious Chinese commodity: a plague. The article argues that rethinking responses to the plague through the history of material culture can further our understanding of the political consequences of disease's entanglement with economic and racial categories, while demonstrating the extent to which colonial agents "thought through things."

  7. Where does human plague still persist in Latin America?

    Science.gov (United States)

    Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Galan, Deise I; Bertherat, Eric; Ruiz, Alfonso; Dumit, Elsy; Gabastou, Jean Marc; Espinal, Marcos A

    2014-02-01

    Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899-2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested.

  8. Where Does Human Plague Still Persist in Latin America?

    Science.gov (United States)

    Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Galan, Deise I.; Bertherat, Eric; Ruiz, Alfonso; Dumit, Elsy; Gabastou, Jean Marc; Espinal, Marcos A.

    2014-01-01

    Background Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. Aims The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Methods Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Results Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899–2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Discussion Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested. PMID:24516682

  9. Where does human plague still persist in Latin America?

    Directory of Open Access Journals (Sweden)

    Maria Cristina Schneider

    2014-02-01

    Full Text Available Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru.The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention.Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties. Selected demographic, socioeconomic, and environmental variables were described.Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899-2012. Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level.Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested.

  10. Plague in Iran: its history and current status.

    Science.gov (United States)

    Hashemi Shahraki, Abdolrazagh; Carniel, Elizabeth; Mostafavi, Ehsan

    2016-01-01

    Plague remains a public health concern worldwide, particularly in old foci. Multiple epidemics of this disease have been recorded throughout the history of Iran. Despite the long-standing history of human plague in Iran, it remains difficult to obtain an accurate overview of the history and current status of plague in Iran. In this review, available data and reports on cases and outbreaks of human plague in the past and present in Iran and in neighboring countries were collected, and information was compiled regarding when, where, and how many cases occurred. This paper considers the history of plague in Persia (the predecessor of today's Iran) and has a brief review of plague in countries in the World Health Organization Eastern Mediterranean Region, including a range of countries in the Middle East and North Africa. Since Iran has experienced outbreaks of plague for several centuries, neighboring countries have reported the disease in recent years, the disease can be silent for decades, and the circulation of Yersinia pestis has been reported among rodents and dogs in western Iran, more attention should be paid to disease monitoring in areas with previously reported human cases and in high-risk regions with previous epizootic and enzootic activity.

  11. Plague in Iran: its history and current status

    Directory of Open Access Journals (Sweden)

    Abdolrazagh Hashemi Shahraki

    2016-07-01

    Full Text Available OBJECTIVES: Plague remains a public health concern worldwide, particularly in old foci. Multiple epidemics of this disease have been recorded throughout the history of Iran. Despite the long-standing history of human plague in Iran, it remains difficult to obtain an accurate overview of the history and current status of plague in Iran. METHODS: In this review, available data and reports on cases and outbreaks of human plague in the past and present in Iran and in neighboring countries were collected, and information was compiled regarding when, where, and how many cases occurred. RESULTS: This paper considers the history of plague in Persia (the predecessor of today’s Iran and has a brief review of plague in countries in the World Health Organization Eastern Mediterranean Region, including a range of countries in the Middle East and North Africa. CONCLUSIONS: Since Iran has experienced outbreaks of plague for several centuries, neighboring countries have reported the disease in recent years, the disease can be silent for decades, and the circulation of Yersinia pestis has been reported among rodents and dogs in western Iran, more attention should be paid to disease monitoring in areas with previously reported human cases and in high-risk regions with previous epizootic and enzootic activity.

  12. Plague: A Millenary Infectious Disease Reemerging in the XXI Century.

    Science.gov (United States)

    Grácio, A J Dos Santos; Grácio, Maria Amélia A

    2017-01-01

    Plague, in the Middle Ages known as Black Death, continues to occur at permanent foci in many countries, in Africa, Asia, South America, and even the USA. During the last years outbreaks were reported from at least 3 geographical areas, in all cases after tens of years without reported cases. The recent human plague outbreaks in Libya and Algeria suggest that climatic and other environmental changes in Northern Africa may be favourable for Y. pestis epidemiologic cycle. If so, other Northern Africa countries with plague foci also may be at risk for outbreaks in the near future. It is important to remember that the danger of plague reoccurrence is not limited to the known natural foci, for example, those of Algeria, Angola, and Madagascar. In a general context, it is important that governments know the dangerous impact that this disease may have and that the health and medical community be familiar with the epidemiology, symptoms, treatment, and control of plague, so an appropriated and timely response can be delivered should the worst case happen. Plague can be used as a potential agent of bioterrorism. We have concluded that plague is without a doubt a reemerging infectious disease.

  13. Plague: A Millenary Infectious Disease Reemerging in the XXI Century

    Directory of Open Access Journals (Sweden)

    A. J. dos Santos Grácio

    2017-01-01

    Full Text Available Plague, in the Middle Ages known as Black Death, continues to occur at permanent foci in many countries, in Africa, Asia, South America, and even the USA. During the last years outbreaks were reported from at least 3 geographical areas, in all cases after tens of years without reported cases. The recent human plague outbreaks in Libya and Algeria suggest that climatic and other environmental changes in Northern Africa may be favourable for Y. pestis epidemiologic cycle. If so, other Northern Africa countries with plague foci also may be at risk for outbreaks in the near future. It is important to remember that the danger of plague reoccurrence is not limited to the known natural foci, for example, those of Algeria, Angola, and Madagascar. In a general context, it is important that governments know the dangerous impact that this disease may have and that the health and medical community be familiar with the epidemiology, symptoms, treatment, and control of plague, so an appropriated and timely response can be delivered should the worst case happen. Plague can be used as a potential agent of bioterrorism. We have concluded that plague is without a doubt a reemerging infectious disease.

  14. Venice: a meeting, a plague, a death

    Directory of Open Access Journals (Sweden)

    Óscar Botasso

    2008-10-01

    Full Text Available Death in Venice is based on the novella of the same name by Thomas Mann, except that in the cinema version the main character, Gustav von Aschenbach, is a musician instead of a writer. Owing to poetic license not always within the layman’s grasp, Luchino Visconti also wished to identify the artist with Gustav Mahler. Beyond such dissimilarities, however, the film is a feasible recreation of the story and a faithful reconstruction of those times: a Venice divorced from its former splendor and invaded by a plague and yet at the same time still able to evoke the captivating, nostalgic legacy of its magnificent past. An ideal scenario indeed for the musical ideas of Mahler, and perfectly reflected in the Midnight Song and the adagietto of his third and fifth symphonies.

  15. Plague and landscape resilience in premodern Iceland

    Science.gov (United States)

    Streeter, Richard; Dugmore, Andrew J.; Vésteinsson, Orri

    2012-01-01

    In debates on societal collapse, Iceland occupies a position of precarious survival, defined by not becoming extinct, like Norse Greenland, but having endured, sometimes by the narrowest of margins. Classic decline narratives for late medieval to early modern Iceland stress compounding adversities, where climate, trade, political domination, unsustainable practices, and environmental degradation conspire with epidemics and volcanism to depress the Icelanders and turn the once-proud Vikings and Saga writers into one of Europe's poorest nations. A mainstay of this narrative is the impact of incidental setbacks such as plague and volcanism, which are seen to have compounded and exacerbated underlying structural problems. This research shows that this view is not correct. We present a study of landscape change that uses 15 precisely dated tephra layers spanning the whole 1,200-y period of human settlement in Iceland. These tephras have provided 2,625 horizons of known age within 200 stratigraphic sections to form a high-resolution spatial and temporal record of change. This finding shows short-term (50 y) declines in geomorphological activity after two major plagues in A.D. 15th century, variations that probably mirrored variations in the population. In the longer term, the geomorphological impact of climate changes from the 14th century on is delayed, and landscapes (as well as Icelandic society) exhibit resilience over decade to century timescales. This finding is not a simple consequence of depopulation but a reflection of how Icelandic society responded with a scaling back of their economy, conservation of core functionality, and entrenchment of the established order. PMID:22371601

  16. Knowledge and practices related to plague in an endemic area of Uganda.

    Science.gov (United States)

    Kugeler, Kiersten J; Apangu, Titus; Forrester, Joseph D; Griffith, Kevin S; Candini, Gordian; Abaru, Janet; Okoth, Jimmy F; Apio, Harriet; Ezama, Geoffrey; Okello, Robert; Brett, Meghan; Mead, Paul

    2017-11-01

    Plague is a virulent zoonosis reported most commonly from Sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs the development of educational efforts to reduce plague mortality. A multi-stage cluster-sampled survey of 420 households was conducted in the plague-endemic West Nile region of Uganda to assess knowledge of symptoms and causes of plague and health care-seeking practices. Most (84%) respondents were able to correctly describe plague symptoms; approximately 75% linked plague with fleas and dead rats. Most respondents indicated that they would seek health care at a clinic for possible plague; however plague-like symptoms were reportedly common, and in practice, persons sought care for those symptoms at a health clinic infrequently. Persons in the plague-endemic region of Uganda have a high level of understanding of plague, yet topics for targeted educational messages are apparent. Published by Elsevier Ltd.

  17. Transmission dynamics of primary pneumonic plague in the USA.

    Science.gov (United States)

    Hinckley, A F; Biggerstaff, B J; Griffith, K S; Mead, P S

    2012-03-01

    Plague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R(0)) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

  18. Plague in Arab Maghreb, 1940-2015: a review

    Directory of Open Access Journals (Sweden)

    Maliya Alia Malek

    2016-06-01

    Full Text Available We reviewed the epidemiology of 49 plague outbreaks which resulted in about 7,612 cases in 30 localities in the Arabic Maghreb (Mauritania, Morocco, Algeria, Tunisia, Libya and Egypt over 75 years. Between 1940 and 1950, most cases recorded in Morocco (75% and Egypt (20%, resulted from plague imported to Mediterranean harbours and transmitted by rat ectoparasites. In contrast, the re-emergence of plague in the southern part of Western Sahara in 1953 and in northeast Libya in 1976, was traced to direct contact between nomadic populations and infected goats and camels in natural foci, including the consumption of contaminated meat, illustrating this neglected oral route of contamination. Further familial outbreaks were traced to human ectoparasite transmission. Efforts to identify the factors contributing to natural foci may guide where to focus the surveillance of sentinel animals in order to eradicate human plague, if not Y. pestis from the Arab Maghreb.

  19. Understanding the persistence of plague foci in Madagascar.

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    2013-11-01

    Full Text Available Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  20. Understanding the Persistence of Plague Foci in Madagascar: e2382

    National Research Council Canada - National Science Library

    Voahangy Andrianaivoarimanana; Katharina Kreppel; Nohal Elissa; Jean-Marc Duplantier; Elisabeth Carniel; Minoarisoa Rajerison; Ronan Jambou

    2013-01-01

    .... The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection...

  1. Understanding the persistence of plague foci in Madagascar

    National Research Council Canada - National Science Library

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    .... The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection...

  2. Human activity spaces and plague risks in three contrasting ...

    African Journals Online (AJOL)

    Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania. Proches Hieronimo, Hubert Gulinck, Didas N. Kimaro, Loth S. Mulungu, Nganga I. Kihupi, Balthazar M. Msanya, Herwig Leirs, Jozef A. Deckers ...

  3. Understanding the persistence of plague foci in Madagascar.

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-11-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  4. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  5. Sylvatic plague vaccine and management of prairie dogs

    Science.gov (United States)

    Rocke, Tonie E.

    2012-01-01

    Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at the University of Wisconsin (UW), have developed a sylvatic plague vaccine that shows great promise in protecting prairie dogs against plague (Mencher and others, 2004; Rocke and others, 2010). Four species of prairie dogs reside in the United States and Canada, and all are highly susceptible to plague and regularly experience outbreaks with devastating losses. Along with habitat loss and poisoning, plague has contributed to a significant historical decline in prairie dog populations. By some estimates, prairie dogs now occupy only 1 to 2 percent of their former range (Proctor and others, 2006), with prairie dog colonies being now much smaller and fragmented than they were historically, making individual colonies more vulnerable to elimination by plague (Antolin and others, 2002). At least one species, the Utah prairie dog (Cynomys parvidens) is listed by the U.S. Fish and Wildlife Service (FWS) as "threatened." Controlling plague is a vital concern for ongoing management and conservation efforts for prairie dogs. Current efforts to halt the spread of plague in prairie dog colonies typically rely on dusting individual prairie dog burrows with pesticides to kill plague-infected fleas. Although flea-control insecticides, such as deltamethrin, are useful in stopping plague outbreaks in these prairie dog colonies, dusting of burrows is labor intensive and time consuming and may affect other insects and arthropods. As an alternative approach, NWHC and UW scientists developed a sylvatic plague vaccine (SPV) for prairie dogs that can be delivered via oral bait. Laboratory studies have shown that consumption of this vaccine-laden bait by different prairie dog species results in significant protection against plague infection that can last for at least 9 months (Rocke and others, 2010; Rocke, unpublished). Work has now shifted to optimizing baits and distribution methods for

  6. [The pathogenic ecology research on plague in Qinghai plateau].

    Science.gov (United States)

    Dai, Rui-xia; Wei, Bai-qing; Li, Cun-xiang; Xiong, Hao-ming; Yang, Xiao-yan; Fan, Wei; Qi, Mei-ying; Jin, Juan; Wei, Rong-jie; Feng, Jian-ping; Jin, Xing; Wang, Zu-yun

    2013-12-01

    To study the pathogenic ecology characteristics of plague in Qinghai plateau. Applied molecular biology techniques, conventional technologies and geographic information system (GIS) to study phenotypic traits, plasmid spectrum, genotype, infected host and media spectrum etc.of 952 Yersinia pestis strains in Qinghai plateau plague foci, which were separated from different host and media in different regions during 1954 to 2012. The ecotypes of these strains were Qingzang plateau (91.49%, 871/952),Qilian mountain (6.41%, 61/952) and Microtus fuscus (1.26%, 12/952).83.6% (796/952) of these strains contained all the 4 virulence factors (Fr1, Pesticin1,Virulence antigen, and Pigmentation), 93.26% (367/392) were velogenic strains confirmed by virulence test.725 Yersinia pestis strains were separated from Qinghai plateau plague foci carried 9 kinds of plasmid, among which 713 strains from Marmot himalayan plague foci carried 9 kinds of plasmid, the Mr were 6×10(6), 7×10(6), 23×10(6), 27×10(6), 30×10(6), 45×10(6), 52×10(6), 65×10(6) and 92×10(6) respectively. 12 Yersinia pestis strains were separated from Microtus fuscus plague foci carried only 3 kinds of plasmid, the Mr were 6×10(6), 45×10(6), 65×10(6). Meanwhile, the strains carrying large plasmid (52×10(6), 65×10(6) and 92×10(6)) were only distributed in particular geographical location, which had the category property. The research also confirmed that 841 Yersinia pestis strains from two kinds of plague foci in Qinghai plateau had 11 genomovars. The strains of Marmot himalayan plague foci were given priority to genomovar 5 and 8, amounted to 611 strains, genomovar 8 accounted for 56.00% (471/841), genomovar 5 accounted for 23.07% (194/841). Besides, 3 new genomovars, including new 1(62 strains), new 2(52 strains), new 3(48 strains) were newly founded, and 12 strains of Microtus fuscus plague foci were genomovar 14. The main host and media of Qinghai plateau plague foci directly affected the spatial

  7. Understanding the persistence of plague foci in Madagascar.

    OpenAIRE

    Voahangy Andrianaivoarimanana; Katharina Kreppel; Nohal Elissa; Jean-Marc Duplantier; Elisabeth Carniel; Minoarisoa Rajerison; Ronan Jambou

    2013-01-01

    International audience; Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The bla...

  8. Plagued by kindness: contagious sympathy in Shakespearean drama.

    Science.gov (United States)

    Langley, Eric

    2011-12-01

    This article considers Shakespeare's metaphors of transmission, contagion and infection in the light of period plague tracts, medical treatises and plague time literature. The author demonstrates how period conceptions of disease are predicated upon a notion of sympathetic transference and, consequently, how kindness, likeness and communication between characters in Shakespearean drama are complicated and fraught with period specific anxiety. This article situates Shakespearean literary texts within a precise historical and medical moment, considering how scientific conceptions contaminate dramatic text.

  9. Plague in Lushoto district, Tanzania, 1980-1988.

    Science.gov (United States)

    Kilonzo, B S; Mbise, T J; Makundi, R H

    1992-01-01

    Rodents were live-trapped in selected plague-inflicted villages from June 1980 to March 1988. Flea infestation rates were determined and the animals were serologically tested for plague. Clinically suspected and clinically healthy people in the affected areas were similarly tested for plague antibodies. Of 1596 rodent sera tested, 91 (5.7%) were positive for plague. These were mostly from Rattus rattus, Mastomys natalensis, Otomys spp. and Pelomys fallax. A total of 1772 fleas, of which Dinopsyllus lypusus, Xenopsylla brasiliensis and Ctenophthalmus calceatus comprised the largest proportion, was collected from the captured rodents. Total flea indices ranged from 0.67 to 1.12 fleas per rodent. A total of 2809 human cases and a mortality rate of 10.2% were recorded in 1980-1988. It was concluded that most rodent species in the area were suitable reservoirs of plague and that D. lypusus, X. brasiliensis and C. calceatus were probably responsible for transmitting the pathogen. Lack of effective quarantine measures during outbreaks was partly responsible for the spread of the disease to many villages, while inadequate rodent and flea control and poor sanitary measures could be responsible for continued outbreaks of plague in the area.

  10. Resistance to plague among black-tailed prairie dog populations

    Science.gov (United States)

    Rocke, Tonie E.; Williamson, Judy; Cobble, Kacy R.; Busch, Joseph D.; Antolin, Michael F.; Wagner, David M.

    2012-01-01

    In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (pdogs were quite similar in their response, with overall survival rates of 50% and 60%, respectively. Prairie dogs from these states were heterogenous in their response, with some animals dying at the lowest dose (37% and 20%, respectively) and some surviving even at the highest dose (29% and 40%, respectively). Microsatellite analysis revealed that all three groups were distinct genetically, but further studies are needed to establish a genetic basis for the observed differences in plague resistance.

  11. The Eyam plague revisited: did the village isolation change transmission from fleas to pulmonary?

    Science.gov (United States)

    Massad, E; Coutinho, F A B; Burattini, M N; Lopez, L F

    2004-01-01

    Back in the 17th century the Derbyshire village of Eyam fell victim to the Black Death, which is thought to have arrived from London in some old clothes brought by a travelling tailor. The village population was 350 at the commencement of plague, of which only 83 survived. Led by the church leaders, the village community realized that the whole surrounding region was at risk from the epidemic, and therefore decided to seal themselves off from the other surrounding villages. In the first 275 days of the outbreak, transmission was predominantly from infected fleas to susceptible humans. From then onward, mortality sharply increased, which indicates a changing in transmission pattern. We hypothesize that the confinement facilitated the spread of the infection by increasing the contact rate through direct transmission among humans. This would be more consistent with pulmonary plague, a deadlier form of the disease. In order to test the above hypothesis we designed a mathematical model for plague dynamics, incorporating both the indirect (fleas-rats-humans) and direct (human-to-human) transmissions of the infection. Our results show remarkable agreement between data and the model, lending support to our hypotheses. The Eyam plague episode is celebrated as a remarkable act of collective self-sacrifice. However, to the best of our knowledge, there were no evidence before that the confinement actually increased the burden payed by the commoners. In the light of our results, it can be said that the hypothesis that confinement facilitated the spread of the infection by increasing the contact rate through direct transmission is plausible.

  12. Persistence of black-tailed prairie-dog populations affected by plague in northern Colorado, USA.

    Science.gov (United States)

    George, Dylan B; Webb, Colleen T; Pepin, Kim M; Savage, Lisa T; Antolini, Michael F

    2013-07-01

    The spatial distribution of prairie dog (Cynomys ludovicianus) colonies in North America has changed from large, contiguous populations to small, isolated colonies in metapopulations. One factor responsible for this drastic change in prairie-dog population structure is plague (caused by the bacterium Yersinia pestis). We fit stochastic patch occupancy models to 20 years of prairie-dog colony occupancy data from two discrete metapopulations (west and east) in the Pawnee National Grassland in Colorado, USA, that differ in connectivity among suitable habitat patches. We conducted model selection between two hypothesized modes of plague movement: independent of prairie-dog dispersal (colony-area) vs. plague movement consistent with prairie-dog dispersal (connectivity to extinct colonies). The best model, which fit the data well (area under the curve [AUC]: 0.94 west area; 0.79 east area), revealed that over time the proportion of extant colonies was better explained by colony size than by connectivity to extinct (plagued) colonies. The idea that prairie dogs are not likely to be the main vector that spreads Y. pestis across the landscape is supported by the observation that colony extinctions are primarily caused by plague, prairie-dog dispersal is short range, and connectivity to extinct colonies was not selected as a factor in the models. We also conducted simulations with the best model to examine long-term patterns of colony occupancy and persistence of prairie-dog metapopulations. In the case where the metapopulations persist, our model predicted that the western metapopulation would have a colony occupancy rate approximately 2.5 times higher than that of the eastern metapopulation (-50% occupied colonies vs. 20%) in 50 years, but that the western metapopulation has -80% chance of extinction in 100 years while the eastern metapopulation has a less than 25% chance. Extinction probability of individual colonies depended on the frequency with which colonies of the

  13. The Rufiji River flood: plague or blessing?

    Science.gov (United States)

    Duvail, Stéphanie; Hamerlynck, Olivier

    2007-10-01

    The building of a large multipurpose dam is planned at Stiegler's Gorge on the Rufiji River (Tanzania). Both national and local authorities have strongly emphasised the flood control aspect of the dam as they see the Rufiji floods as a major constraint to development. Though it is true that the Rufiji River has a high flow variability at various timescales, the flood perception in local communities differs from this view. The floods, essential for the sustenance of floodplain fertility, and therefore of the farming system, and vital to the productivity of most of the natural resources on which local communities depend, are perceived as a blessing, whilst droughts and the absence of regular flooding are perceived as the main threat. Historically, most of the food shortages in Rufiji District are associated with drought years and the myth of "the flood as a plague" emerged only in the late 1960s during the Ujamaa villagisation policy. The persistence of this myth is favoured by the inadequate assessment of the complexity of the local economies by the District technical staff. This difference in perception of the flood has major implications for development options. Under the current dam design, the alteration of the flooding pattern would have negative consequences for the downstream wetland and forest ecosystems and the flood-associated livelihoods of some 150,000 people. A cost-benefit analysis of flood control measures and a study of a dam design that would maintain the beneficial aspects of flooding should be accorded the highest priority.

  14. Potential corridors and barriers for plague spread in Central Asia.

    Science.gov (United States)

    Wilschut, Liesbeth I; Addink, Elisabeth A; Heesterbeek, Hans; Heier, Lise; Laudisoit, Anne; Begon, Mike; Davis, Stephen; Dubyanskiy, Vladimir M; Burdelov, Leonid A; de Jong, Steven M

    2013-10-31

    Plague (Yersinia pestis infection) is a vector-borne disease which caused millions of human deaths in the Middle Ages. The hosts of plague are mostly rodents, and the disease is spread by the fleas that feed on them. Currently, the disease still circulates amongst sylvatic rodent populations all over the world, including great gerbil (Rhombomys opimus) populations in Central Asia. Great gerbils are social desert rodents that live in family groups in burrows, which are visible on satellite images. In great gerbil populations an abundance threshold exists, above which plague can spread causing epizootics. The spatial distribution of the host species is thought to influence the plague dynamics, such as the direction of plague spread, however no detailed analysis exists on the possible functional or structural corridors and barriers that are present in this population and landscape. This study aims to fill that gap. Three 20 by 20 km areas with known great gerbil burrow distributions were used to analyse the spatial distribution of the burrows. Object-based image analysis was used to map the landscape at several scales, and was linked to the burrow maps. A novel object-based method was developed - the mean neighbour absolute burrow density difference (MNABDD) - to identify the optimal scale and evaluate the efficacy of using landscape objects as opposed to square cells. Multiple regression using raster maps was used to identify the landscape-ecological variables that explain burrow density best. Functional corridors and barriers were mapped using burrow density thresholds. Cumulative resistance of the burrow distribution to potential disease spread was evaluated using cost distance analysis. A 46-year plague surveillance dataset was used to evaluate whether plague spread was radially symmetric. The burrow distribution was found to be non-random and negatively correlated with Greenness, especially in the floodplain areas. Corridors and barriers showed a mostly NWSE

  15. Potential corridors and barriers for plague spread in central Asia

    Science.gov (United States)

    2013-01-01

    Background Plague (Yersinia pestis infection) is a vector-borne disease which caused millions of human deaths in the Middle Ages. The hosts of plague are mostly rodents, and the disease is spread by the fleas that feed on them. Currently, the disease still circulates amongst sylvatic rodent populations all over the world, including great gerbil (Rhombomys opimus) populations in Central Asia. Great gerbils are social desert rodents that live in family groups in burrows, which are visible on satellite images. In great gerbil populations an abundance threshold exists, above which plague can spread causing epizootics. The spatial distribution of the host species is thought to influence the plague dynamics, such as the direction of plague spread, however no detailed analysis exists on the possible functional or structural corridors and barriers that are present in this population and landscape. This study aims to fill that gap. Methods Three 20 by 20 km areas with known great gerbil burrow distributions were used to analyse the spatial distribution of the burrows. Object-based image analysis was used to map the landscape at several scales, and was linked to the burrow maps. A novel object-based method was developed – the mean neighbour absolute burrow density difference (MNABDD) – to identify the optimal scale and evaluate the efficacy of using landscape objects as opposed to square cells. Multiple regression using raster maps was used to identify the landscape-ecological variables that explain burrow density best. Functional corridors and barriers were mapped using burrow density thresholds. Cumulative resistance of the burrow distribution to potential disease spread was evaluated using cost distance analysis. A 46-year plague surveillance dataset was used to evaluate whether plague spread was radially symmetric. Results The burrow distribution was found to be non-random and negatively correlated with Greenness, especially in the floodplain areas. Corridors and

  16. Are plague pits of particular use to palaeoepidemiologists?

    Science.gov (United States)

    Waldron, H A

    2001-02-01

    The demography and pattern of disease of skeletal assemblages may not accurately reflect those of the living population of which they were once a part. The hypothesis tested here was that skeletons from a mass disaster would more closely approximate to a living population than those from a conventional cemetery. Six hundred skeletons recovered from a Black Death plague pit in London were compared with 236 skeletons recovered from an overlying medieval cemetery. Age and sex were determined by standard anthropological means by a single observer and adjustments were made to correct for those skeletons for which either or both could not be established. An estimate of age structure of the living medieval population of London was made, using model life tables. The age and sex distribution and the pattern of disease in the Black Death skeletons did not differ substantially from those in the control group of skeletons. Both assemblages tended to overestimate the numbers in the younger age groups of the model population and underestimate the numbers in the oldest age group. On the evidence from this single site, a skeletal assemblage from a mass disaster does not provide a better representation of the living population from which it was derived than that from a conventional cemetery.

  17. [ON SOME DEBATABLE PROBLEMS OF THE NATURAL NIDALITY OF PLAGUE].

    Science.gov (United States)

    Verzhutsky, D B; Balakhonov, S V

    2016-01-01

    The communication substantiates the opinion that the theory of natural nidality of plague; which is based on the fundamental recognition that fleas play a leading role in the transmission and accumulation of the plague pathogen, cannot be disproved or substantially changed on the alternative weakly reasoned assumptions and hypotheses. All its "bottlenecks" are quite understandable when considering the long-term volumetric materials that have been gathered directly in nature and generalized in multiple publications. Plague is an obligate transmissive infection; its, agent is a highly specialized parasite that is completely associated in its vital activity with the only group of the blood-sucking insects--fleas and that is transmitted through periodic colonization of warm-blooded animals for a short time. All other types of plague microbe persistence in nature are either occasional or minor and do not play any significant role in pathogen persistence in the natural foci of this disease. There are no strong grounds for seriously considering the attempts to revise the main points of the theory of natural nidality of plague, which are widely held in current academic publications.

  18. A Taxonomic Update of Small Mammal Plague Reservoirs in South America.

    Science.gov (United States)

    Bonvicino, Cibele R; Oliveira, João A; Cordeiro-Estrela, Pedro; D'andrea, Paulo S; Almeida, Alzira M P

    2015-10-01

    Plague is a disease of epidemic potential that may emerge with discontinuous outbreaks. In South America, 50 wild rodent species have been identified as plague reservoirs, in addition to one lagomorph and two marsupials. To review the nomenclature of plague reservoirs, we examined specimens collected in plague foci, carried out new surveys in Brazilian plague regions, and re-evaluated the nomenclature of South American reservoirs on the basis of the current literature. Five of the 15 species involved with plague in Argentina, three of 10 species involved with plague in Bolivia, three of the seven species involved with plague in Peru, five of the nine species involved with plague in Ecuador, and six of the nine species involved with plague in Brazil have undergone taxonomic changes. In the last 20 years, plague cases were recorded in Bolivia, Brazil, Ecuador, and Peru. These four countries have a high rodent species richness in plague foci, a fact that may be decisive for the maintenance of plague in the wild.

  19. CCR5 polymorphism and plague resistance in natural populations of the black rat in Madagascar.

    Science.gov (United States)

    Tollenaere, C; Rahalison, L; Ranjalahy, M; Rahelinirina, S; Duplantier, J-M; Brouat, C

    2008-12-01

    Madagascar remains one of the world's largest plague foci. The black rat, Rattus rattus, is the main reservoir of plague in rural areas. This species is highly susceptible to plague in plague-free areas (low-altitude regions), whereas rats from the plague focus areas (central highlands) have evolved a disease-resistance polymorphism. We used the candidate gene CCR5 to investigate the genetic basis of plague resistance in R. rattus. We found a unique non-synonymous substitution (H184R) in a functionally important region of the gene. We then compared (i) CCR5 genotypes of dying and surviving plague-challenged rats and (ii) CCR5 allelic frequencies in plague focus and plague-free populations. Our results suggested a higher prevalence of the substitution in resistant animals compared to susceptible individuals, and a tendency for higher frequencies in plague focus areas compared to plague-free areas. Therefore, the CCR5 polymorphism may be involved in Malagasy black rat plague resistance. CCR5 and other undetermined plague resistance markers may provide useful biological information about host evolution and disease dynamics.

  20. Wet climate and transportation routes accelerate spread of human plague

    Science.gov (United States)

    Xu, Lei; Stige, Leif Chr.; Kausrud, Kyrre Linné; Ben Ari, Tamara; Wang, Shuchun; Fang, Xiye; Schmid, Boris V.; Liu, Qiyong; Stenseth, Nils Chr.; Zhang, Zhibin

    2014-01-01

    Currently, large-scale transmissions of infectious diseases are becoming more closely associated with accelerated globalization and climate change, but quantitative analyses are still rare. By using an extensive dataset consisting of date and location of cases for the third plague pandemic from 1772 to 1964 in China and a novel method (nearest neighbour approach) which deals with both short- and long-distance transmissions, we found the presence of major roads, rivers and coastline accelerated the spread of plague and shaped the transmission patterns. We found that plague spread velocity was positively associated with wet conditions (measured by an index of drought and flood events) in China, probably due to flood-driven transmission by people or rodents. Our study provides new insights on transmission patterns and possible mechanisms behind variability in transmission speed, with implications for prevention and control measures. The methodology may also be applicable to studies of disease dynamics or species movement in other systems. PMID:24523275

  1. Plague: A Disease Which Changed the Path of Human Civilization.

    Science.gov (United States)

    Bramanti, Barbara; Stenseth, Nils Chr; Walløe, Lars; Lei, Xu

    2016-01-01

    Plague caused by Yersinia pestis is a zoonotic infection, i.e., it is maintained in wildlife by animal reservoirs and on occasion spills over into human populations, causing outbreaks of different entities. Large epidemics of plague, which have had significant demographic, social, and economic consequences, have been recorded in Western European historical documents since the sixth century. Plague has remained in Europe for over 1400 years, intermittently disappearing, yet it is not clear if there were reservoirs for Y. pestis in Western Europe or if the pathogen was rather reimported on different occasions from Asian reservoirs by human agency. The latter hypothesis thus far seems to be the most plausible one, as it is sustained by both ecological and climatological evidence, helping to interpret the phylogeny of this bacterium.

  2. [Advance to the research of the climate factor effect on the distribution of plague].

    Science.gov (United States)

    Zhang, A P; Wei, R J; Xiong, H M; Wang, Z Y

    2016-05-01

    Plague is an anthropozoonotic disease caused by the Yersinia pestis ,which developed by many factors including local climate factors. In recent years, more and more studies on the effects of climate on plague were conducted. According to the researches, climate factors (mainly the rainfall and temperature) affected the development and distribution of plague by influencing the abundance of plague host animals and fleas index. The climate also affected the epidemic dynamics and the scope of plague. There were significant differences existing in the influence of climate on the palgue developed in the north and south China. In the two different plague epidemic systems, the solitary Daurian ground squirrel-flea-plague and the social Mongolian gerbil-flea-plague, the obvious population differences existed among the responses of the host animal to the climate changes. Although the internal relationship between the rainfall, the flea index, the density of rodents and the plague supported the nutritional cascade hypothesis, it can not prove that there is a clear causality between the occurrence of plague and rainfall. So the influence of climate factors on plague distribution can only be used for early forecasting and warning of the plague.

  3. Susceptibility to Yersinia pestis experimental infection in wild Rattus rattus, reservoir of plague in Madagascar.

    Science.gov (United States)

    Tollenaere, C; Rahalison, L; Ranjalahy, M; Duplantier, J-M; Rahelinirina, S; Telfer, S; Brouat, C

    2010-06-01

    In Madagascar, the black rat, Rattus rattus, is the main reservoir of plague (Yersinia pestis infection), a disease still responsible for hundreds of cases each year in this country. This study used experimental plague challenge to assess susceptibility in wild-caught rats to better understand how R. rattus can act as a plague reservoir. An important difference in plague resistance between rat populations from the plague focus (central highlands) and those from the plague-free zone (low altitude area) was confirmed to be a widespread phenomenon. In rats from the plague focus, we observed that sex influenced plague susceptibility, with males slightly more resistant than females. Other individual factors investigated (weight and habitat of sampling) did not affect plague resistance. When infected at high bacterial dose (more than 10⁵ bacteria injected), rats from the plague focus died mainly within 3-5 days and produced specific antibodies, whereas after low-dose infection (plague resistance level and the course of infection in the black rat would contribute to a better understanding of plague circulation in Madagascar.

  4. Paleoproteomics of the Dental Pulp: The plague paradigm.

    Science.gov (United States)

    Barbieri, Rémi; Mekni, Rania; Levasseur, Anthony; Chabrière, Eric; Signoli, Michel; Tzortzis, Stéfan; Aboudharam, Gérard; Drancourt, Michel

    2017-01-01

    Chemical decomposition and fragmentation may limit the detection of ancient host and microbial DNA while some proteins can be detected for extended periods of time. We applied paleoproteomics on 300-year-old dental pulp specimens recovered from 16 individuals in two archeological funeral sites in France, comprising one documented plague site and one documented plague-negative site. The dental pulp paleoproteome of the 16 teeth comprised 439 peptides representative of 30 proteins of human origin and 211 peptides representative of 27 proteins of non-human origin. Human proteins consisted of conjunctive tissue and blood proteins including IgA immunoglobulins. Four peptides were indicative of three presumable Yersinia pestis proteins detected in 3/8 dental pulp specimens from the plague-positive site but not in the eight dental pulp specimens collected in the plague-negative site. Paleoproteomics applied to the dental pulp is a new and innovative approach to screen ancient individuals for the detection of blood-borne pathogens and host inflammatory response.

  5. Genome sequence of Yersinia pestis, the causative agent of plague.

    Science.gov (United States)

    Parkhill, J; Wren, B W; Thomson, N R; Titball, R W; Holden, M T; Prentice, M B; Sebaihia, M; James, K D; Churcher, C; Mungall, K L; Baker, S; Basham, D; Bentley, S D; Brooks, K; Cerdeño-Tárraga, A M; Chillingworth, T; Cronin, A; Davies, R M; Davis, P; Dougan, G; Feltwell, T; Hamlin, N; Holroyd, S; Jagels, K; Karlyshev, A V; Leather, S; Moule, S; Oyston, P C; Quail, M; Rutherford, K; Simmonds, M; Skelton, J; Stevens, K; Whitehead, S; Barrell, B G

    2001-10-04

    The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.

  6. Plague Epidemic s in Syria b etween XIII - XV. Centuries

    Directory of Open Access Journals (Sweden)

    Esra ATMACA

    2015-07-01

    Full Text Available Epidemic diseases that cause mass death has been one of the greatest fears of the society in the past century Usually due to poor living conditions, poverty, the inadequate treatment. Plague is one of them. Plague word is sometimes used synonymously with t he word tâûn, sometimes considered to be a greater sense of the Word plague. These outbreaks occured repeatedly in human society and many times occured between XIII - XV. centuries. Our research aims to examine the plague occured in Syria in the Mamluk state domination discussed period. One of the outbreaks have occured in the period between the years 1347 - 1351. Epidemic was looming at the same time with the European named the black death or large extinction. Many people have been killed in Syria as in other places where the epidemic has spread. Rumors about them are given in the source is situated in the form of the issuance of the number of people who died in one day and sometimes the total number of deaths took place at a given date range. In this study, we aimed to determine which is more severe than the others in the outbreak, to assess the rumor about the number of deaths from this cause, to reveal the difficulties of the funeral of the dead, to uncover practices that people do to get rid of this disease.

  7. Plague: Infections of Companion Animals and Opportunities for Intervention

    Directory of Open Access Journals (Sweden)

    Petra C.F. Oyston

    2011-06-01

    Full Text Available Plague is a zoonotic disease, normally circulating in rodent populations, transmitted to humans most commonly through the bite of an infected flea vector. Secondary infection of the lungs results in generation of infectious aerosols, which pose a significant hazard to close contacts. In enzootic areas, plague infections have been reported in owners and veterinarians who come into contact with infected pets. Dogs are relatively resistant, but can import infected fleas into the home. Cats are acutely susceptible, and can present a direct hazard to health. Reducing roaming and hunting behaviours, combined with flea control measures go some way to reducing the risk to humans. Various vaccine formulations have been developed which may be suitable to protect companion animals from contracting plague, and thus preventing onward transmission to man. Since transmission has resulted in a number of fatal cases of plague, the vaccination of domestic animals such as cats would seem a low cost strategy for reducing the risk of infection by this serious disease in enzootic regions.

  8. Observations on the endemicity of plague in Karatu and Ngorongoro ...

    African Journals Online (AJOL)

    Some domestic dogs and cats in the Karatu villages were aseptically bled and similarly tested for plague. Fleas were collected from the examined animals and from randomly selected residential houses. A total of 241 rodents, 1 Crocidura spp, 43 dogs, 12 cats and 4 slender mongooses were involved in the survey.

  9. Plague in Tanzania: An overview | Ziwa | Tanzania Journal of Health ...

    African Journals Online (AJOL)

    Despite the long-standing history of this problem, there have not been recent reviews of the current knowledge on plague in Tanzania. ... strategy, we recommend broader studies that will include the ecology of the pathogen, vectors and potential hosts, identifying the reservoirs, dynamics of infection and landscape ecology.

  10. Observations on the endemicity of plague in Karatu and Ngorongoro ...

    African Journals Online (AJOL)

    Commensal and field rodents and wild small carnivores were live-trapped in five villages of Karatu district and one settlement in the Ngorongoro Conservation Area in Ngorongoro district in Tanzania. Blood samples were taken and serologically tested for plague, using the Blocking ELISA technique. Some domestic dogs ...

  11. MOLECULAR AND EVOLUTIONARY INSIGHTS INTO YERSINIA PESTIS; HARBINGER OF PLAGUE

    Directory of Open Access Journals (Sweden)

    Stephen Anderson

    2013-10-01

    Full Text Available Plague has been the scourge of mankind for millennia; yet it was not until the late 18th Century that its causative agent was identified. Prokaryotic Y. pestis is responsible for plague; bacilli are consumed through arthropod feeding on infected rodential reservoirs. Arthropod uptake is essential for transmission as the bacilli proliferate within their gut before being refluxed into new mammalian hosts. Genomic analysis has elucidated the mechanisms facilitating this cycle along with the means by which bacilli acquire their characteristic virulence. Increasing our understanding of the evolution of Y. pestis provides putative avenues for future research. Whilst plague is considered a disease of the past by many, it interaction with humanity continues across various geographic foci. The rise of antibiotic resistant bacteria threatens to bring this ancient foe once again to the fore through the acquisition of drug resistance. This review will detail notable advances of the past decade enabling the elusive possibility of a universal vaccine for the three manifestations of plague. Development of suitable vaccines before drug resistant strains emerge is paramount. Researchers are pitted in an on-going race against bacterial evolution.

  12. Seasonal fluctuations of small mammal and flea communities in a Ugandan plague focus: evidence to implicate Arvicanthis niloticus and Crocidura spp. as key hosts in Yersinia pestis transmission.

    Science.gov (United States)

    Moore, Sean M; Monaghan, Andrew; Borchert, Jeff N; Mpanga, Joseph T; Atiku, Linda A; Boegler, Karen A; Montenieri, John; MacMillan, Katherine; Gage, Kenneth L; Eisen, Rebecca J

    2015-01-08

    The distribution of human plague risk is strongly associated with rainfall in the tropical plague foci of East Africa, but little is known about how the plague bacterium is maintained during periods between outbreaks or whether environmental drivers trigger these outbreaks. We collected small mammals and fleas over a two year period in the West Nile region of Uganda to examine how the ecological community varies seasonally in a region with areas of both high and low risk of human plague cases. Seasonal changes in the small mammal and flea communities were examined along an elevation gradient to determine whether small mammal and flea populations exhibit differences in their response to seasonal fluctuations in precipitation, temperature, and crop harvests in areas within (above 1300 m) and outside (below 1300 m) of a model-defined plague focus. The abundance of two potential enzootic host species (Arvicanthis niloticus and Crocidura spp.) increased during the plague season within the plague focus, but did not show the same increase at lower elevations outside this focus. In contrast, the abundance of the domestic rat population (Rattus rattus) did not show significant seasonal fluctuations regardless of locality. Arvicanthis niloticus abundance was negatively associated with monthly precipitation at a six month lag and positively associated with current monthly temperatures, and Crocidura spp. abundance was positively associated with precipitation at a three month lag and negatively associated with current monthly temperatures. The abundance of A. niloticus and Crocidura spp. were both positively correlated with the harvest of millet and maize. The association between the abundance of several small mammal species and rainfall is consistent with previous models of the timing of human plague cases in relation to precipitation in the West Nile region. The seasonal increase in the abundance of key potential host species within the plague focus, but not outside of

  13. [The plague reviewed by way of molecular biology].

    Science.gov (United States)

    Carniel, E

    1999-12-01

    The aetiology of plague was first discovered during the third pandemic of the disease occurring in Hong Kong in 1894. After Alexandre Yersin had identified the causal agent (Y. Pestis), Paul-Louis Simond proved the flea's role as vector. These discoveries were of prime importance for the subsequent development of efficient means for fighting plague as well as for preventive and curative treatments and vaccines. Vaccination brought about a sharp decrease in plague mortality and morbidity. However, the disease has never been eradicated. It is still prevalent in various Asian, African and American countries and is among the re-emerging diseases at the present time. The genetic basis of transmission mechanisms and pathogenicity of the bacillus are only beginning to be understood. We now know that the attenuation of the EV76 strain used by Girard and Robic as an anti-plague vaccine in Madagascar is due to the spontaneous excision of a large chromosomal DNA fragment of 102 kb, a part of which contains a group of genes implicated in the pathogenicity and appropriately called high pathogenicity island. These mechanisms of flea bacillus transmission are also beginning to be known. Two bacterial loci participating in the blocking of the ectoparasite's proventriculus have been identified. One is situated next to the high pathogenicity island on the unstable 102 kb chromosomal fragment, the other--on the large 95 kb plasmid specific to Y. pestis. The molecular basis of the bacillus' acquisition of multi-resistance to antibiotics have likewise recently been characterised. However, although Y. pestis is one of the most pathogenic micro-organisms of the bacterial world, the mechanisms responsible for this high level of pathogenecity have still not been identified. This is well worth noting, since a certain number of genes acting as pathogenicity factors in other species are present but altered in Y. pestis. Plague still withholds many secrets.

  14. Knowledge and practices related to plague in an endemic area of Uganda

    Directory of Open Access Journals (Sweden)

    Kiersten J. Kugeler

    2017-11-01

    Full Text Available Background: Plague is a virulent zoonosis reported most commonly from Sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs the development of educational efforts to reduce plague mortality. Methods: A multi-stage cluster-sampled survey of 420 households was conducted in the plague-endemic West Nile region of Uganda to assess knowledge of symptoms and causes of plague and health care-seeking practices. Results: Most (84% respondents were able to correctly describe plague symptoms; approximately 75% linked plague with fleas and dead rats. Most respondents indicated that they would seek health care at a clinic for possible plague; however plague-like symptoms were reportedly common, and in practice, persons sought care for those symptoms at a health clinic infrequently. Conclusions: Persons in the plague-endemic region of Uganda have a high level of understanding of plague, yet topics for targeted educational messages are apparent. Keywords: Plague, Yersinia pestis, Knowledge, Practices, Behaviors, Africa

  15. Practical disinfection chemicals for fishing and crayfishing gear against crayfish plague transfer

    Directory of Open Access Journals (Sweden)

    Jussila J.

    2014-01-01

    Full Text Available We tested four commercial disinfectants against crayfish plague (Aphanomyces astaci spores in both aquatic solutions and with material mimicking fishing and crayfishing gear, e.g. traps, ropes, mesh, etc. The tested disinfectants were Proxitane®5:14, Proxitane®12:20, Wofasteril®E400, Virkon®S and hydrogen peroxide. The effects of the chemicals were initially tested in liquid zoospore cultures and the effective concentrations were then further tested using clean and dirty model materials (PP sheet, nylon rope, cotton fabric contaminated with A. astaci spore solutions. The disinfectants effective against infective crayfish plague spores with both clean and dirty model materials were Proxinate®5:14 (effective concentration was 30 mg·L-1 of PAA and Virkon®S (3 g·L-1, while Proxinate®12:20 (10 mg·L-1 of PAA and Wofasteril®E400 (30 mg·L-1 of PAA worked only with clean model materials. Hydrogen peroxide was not effective in the tested concentrations and conditions. Based on the results, the disinfectants most suitable for the fishing and crayfishing gear disinfection would be Proxitane®5:14 and Virkon®S, with the condition that all the gear should be thoroughly cleaned of organic matter to ensure inactivation of A. astaci spores.

  16. [The Antonine Plague and the decline of the Roman Empire].

    Science.gov (United States)

    Sabbatani, S; Fiorino, S

    2009-12-01

    The Antonine Plague, which flared up during the reign of Marcus Aurelius from 165 AD and continued under the rule of his son Commodus, played such a major role that the pathocenosis in the Ancient World was changed. The spread of the epidemic was favoured by the occurrence of two military episodes in which Marcus Aurelius himself took part: the Parthian War in Mesopotamia and the wars against the Marcomanni in northeastern Italy, in Noricum and in Pannonia. Accounts of the clinical features of the epidemic are scant and disjointed, with the main source being Galen, who witnessed the plague. Unfortunately, the great physician provides us with only a brief presentation of the disease, his aim being to supply therapeutic approaches, thus passing over the accurate description of the disease symptoms. Although the reports of some clinical cases treated by Galen lead us to think that the Antonine plague was caused by smallpox, palaeopathological confirmation is lacking. Some archaeological evidence (such as terracotta finds) from Italy might reinforce this opinion. In these finds, some details can be observed, suggesting the artist's purpose to represent the classic smallpox pustules, typical signs of the disease. The extent of the epidemic has been extensively debated: the majority of authors agree that the impact of the plague was severe, influencing military conscription, the agricultural and urban economy, and depleting the coffers of the State. The Antonine plague affected ancient Roman traditions, also leaving a mark on artistic expression; a renewal of spirituality and religiousness was recorded. These events created the conditions for the spread of monotheistic religions, such as Mithraism and Christianity. This period, characterized by health, social and economic crises, paved the way for the entry into the Empire of neighbouring barbarian tribes and the recruitment of barbarian troops into the Roman army; these events particularly favoured the cultural and

  17. Emergence, spread, persistence and fade-out of sylvatic plague in Kazakhstan

    Science.gov (United States)

    Heier, Lise; Storvik, Geir O.; Davis, Stephen A.; Viljugrein, Hildegunn; Ageyev, Vladimir S.; Klassovskaya, Evgeniya; Stenseth, Nils Chr.

    2011-01-01

    Predicting the dynamics of zoonoses in wildlife is important not only for prevention of transmission to humans, but also for improving the general understanding of epidemiological processes. A large dataset on sylvatic plague in the Pre-Balkhash area of Kazakhstan (collected for surveillance purposes) provides a rare opportunity for detailed statistical modelling of an infectious disease. Previous work using these data has revealed a host abundance threshold for epizootics, and climatic influences on plague prevalence. Here, we present a model describing the local space–time dynamics of the disease at a spatial scale of 20 × 20 km2 and a biannual temporal scale, distinguishing between invasion and persistence events. We used a Bayesian imputation method to account for uncertainties resulting from poor data in explanatory variables and response variables. Spatial autocorrelation in the data was accounted for in imputations and analyses through random effects. The results show (i) a clear effect of spatial transmission, (ii) a high probability of persistence compared with invasion, and (iii) a stronger influence of rodent abundance on invasion than on persistence. In particular, there was a substantial probability of persistence also at low host abundance. PMID:21345866

  18. Sylvatic plague vaccine: A new tool for conservation of threatened and endangered species?

    Science.gov (United States)

    Abbott, Rachel C.; Osorio, Jorge E.; Bunck, Christine M.; Rocke, Tonie E.

    2012-01-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  19. Sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?

    Science.gov (United States)

    Abbott, Rachel C; Osorio, Jorge E; Bunck, Christine M; Rocke, Tonie E

    2012-09-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  20. A Non-Stationary Relationship between Global Climate Phenomena and Human Plague Incidence in Madagascar

    Science.gov (United States)

    Kreppel, Katharina S.; Caminade, Cyril; Telfer, Sandra; Rajerison, Minoarison; Rahalison, Lila; Morse, Andy; Baylis, Matthew

    2014-01-01

    Background Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar. Methodology/principal findings We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation. Conclusions/significance This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar. PMID

  1. A non-stationary relationship between global climate phenomena and human plague incidence in Madagascar.

    Directory of Open Access Journals (Sweden)

    Katharina S Kreppel

    2014-10-01

    Full Text Available Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO. The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD. It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar.We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation.This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.

  2. A non-stationary relationship between global climate phenomena and human plague incidence in Madagascar.

    Science.gov (United States)

    Kreppel, Katharina S; Caminade, Cyril; Telfer, Sandra; Rajerison, Minoarison; Rahalison, Lila; Morse, Andy; Baylis, Matthew

    2014-10-01

    Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar. We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation. This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.

  3. News Reports about Health: Between Heroes and Plagues

    Directory of Open Access Journals (Sweden)

    Acianela Montes de Oca

    2013-12-01

    Full Text Available This research characterizes news reports published in the health sections of two newspapers, El Nacional and El Universal, from 1996 to 2006 from the perspective of the myths. Mytheme analysis and rhetorical figures show that myths more frecuently used were The Hero, The Progress, The Plague and Panacea. From the analysis we concluded that the texts of the health sections of analyzed newspapers show a dangerous world (stalked by The Plague that only the Hero (the doctor can face. Science, technology, modernity, health, The Progress, Panacea, seem a gift rather than a human conquest. If we accept the premise that the myths act unify social representations and introduce a single meaning to the future, these stories express a look of helplessness and uncertainty in illness and risk.

  4. The concept of quarantine in history: from plague to SARS.

    Science.gov (United States)

    Gensini, Gian Franco; Yacoub, Magdi H; Conti, Andrea A

    2004-11-01

    The concept of 'quarantine' is embedded in health practices, attracting heightened interest during episodes of epidemics. The term is strictly related to plague and dates back to 1377, when the Rector of the seaport of Ragusa (then belonging to the Venetian Republic) officially issued a 30-day isolation period for ships, that became 40 days for land travellers. During the next 100 years similar laws were introduced in Italian and in French ports, and they gradually acquired other connotations with respect to their original implementation. Measures analogous to those employed against the plague have been adopted to fight against the disease termed the Great White Plague, i.e. tuberculosis, and in recent times various countries have set up official entities for the identification and control of infections. Even more recently (2003) the proposal of the constitution of a new European monitoring, regulatory and research institution has been made, since the already available system of surveillance has found an enormous challenge in the global emergency of the severe acute respiratory syndrome (SARS). In the absence of a targeted vaccine, general preventive interventions have to be relied upon, including high healthcare surveillance and public information. Quarantine has, therefore, had a rebound of celebrity and updated evidence strongly suggests that its basic concept is still fully valid.

  5. A Personal View of How Paleomicrobiology Aids Our Understanding of the Role of Lice in Plague Pandemics.

    Science.gov (United States)

    Raoult, Didier

    2016-08-01

    We have been involved in the field of paleomicrobiology since 1998, when we used dental pulp to identify Yersinia pestis as the causative agent of the great plague of Marseille (1720). We recently designed a specific technique, "suicide PCR," that can prevent contamination. A controversy arose between two teams, with one claiming that DNA must be altered to amplify it and the other group claiming that demographic data did not support the role of Y. pestis in the Black Death (i.e., the great plague of the Middle Ages). These controversies led us to evaluate other epidemiological models and to propose the body louse as the vector of this pandemic. This proposal was substantiated by experimental models, the recovery of Y. pestis from lice in the Congo, and the identification of epidemics involving both Y. pestis and Bartonella quintana (the agent of trench fever, transmitted by the body louse) in ancient corpses from mass graves. Paleomicrobiology has led to a re-evaluation of plague pandemics.

  6. [Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

    Science.gov (United States)

    Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

    2014-01-01

    Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

  7. Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

    Science.gov (United States)

    Salkeld, Daniel J

    2017-09-01

    The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

  8. Identification of duck plague virus by polymerase chain reaction

    Science.gov (United States)

    Hansen, W.R.; Brown, Sean E.; Nashold, S.W.; Knudson, D.L.

    1999-01-01

    A polymerase chain reaction (PCR) assay was developed for detecting duck plague virus. A 765-bp EcoRI fragment cloned from the genome of the duck plague vaccine (DP-VAC) virus was sequenced for PCR primer development. The fragment sequence was found by GenBank alignment searches to be similar to the 3a?? ends of an undefined open reading frame and the gene for DNA polymerase protein in other herpesviruses. Three of four primer sets were found to be specific for the DP-VAC virus and 100% (7/7) of field isolates but did not amplify DNA from inclusion body disease of cranes virus. The specificity of one primer set was tested with genome templates from other avian herpesviruses, including those from a golden eagle, bald eagle, great horned owl, snowy owl, peregrine falcon, prairie falcon, pigeon, psittacine, and chicken (infectious laryngotracheitis), but amplicons were not produced. Hence, this PCR test is highly specific for duck plague virus DNA. Two primer sets were able to detect 1 fg of DNA from the duck plague vaccine strain, equivalent to five genome copies. In addition, the ratio of tissue culture infectious doses to genome copies of duck plague vaccine virus from infected duck embryo cells was determined to be 1:100, making the PCR assay 20 times more sensitive than tissue culture for detecting duck plague virus. The speed, sensitivity, and specificity of this PCR provide a greatly improved diagnostic and research tool for studying the epizootiology of duck plague. /// Se desarroll?? una prueba de reacci??n en cadena por la polimerasa para detectar el virus de la peste del pato. Un fragmento EcoRI de 765 pares de bases clonado del genoma del virus vacunal de la peste del pato fue secuenciado para la obtenci??n de los iniciadores de la prueba de la reacci??n en cadena por la polimerasa. En investigaciones de alineaci??n en el banco de genes ('GenBank') se encontr?? que la secuencia del fragmento era similar a los extremos 3a?? de un marco de lectura abierto

  9. Study on the movement of Rattus rattus and evaluation of the plague dispersion in Madagascar.

    Science.gov (United States)

    Rahelinirina, Soanandrasana; Duplantier, Jean Marc; Ratovonjato, Jocelyn; Ramilijaona, Olga; Ratsimba, Mamy; Rahalison, Lila

    2010-01-01

    Plague affects mainly the rural areas in the central highlands of Madagascar. Rattus rattus is the main rodent host of Yersinia pestis in these localities. Since the introduction of plague, endemic foci have continued to expand, and spatiotemporal variability in the distribution of human plague has been observed. To assess the movements of R. rattus and evaluate the risk of dispersion of the disease, a field study at the scale of the habitats (houses, hedges of sisals, and rice fields) in the plague villages was carried out during high and low seasons of plague transmission to humans. The systemic oral marker Rhodamine B was used to follow rats' movements. Baits were placed in different habitats, and trapping success was carried out once a month for 3 months after the bait distribution. Plague indicators (reservoirs' abundance, flea index, Y. pestis prevalence in fleas, and Y. pestis antibody prevalence in rats) were determined. The highest abundance of rats and marking efficiency were observed in the sisal hedges and the rice fields. Marked rats were captured most commonly near the points where baits were initially placed. The main movements of rats were observed between the houses and sisal hedges. Major differences were observed between the seasons of high and low plague transmission. During the season of low plague transmission, rats were more abundant in the sisal hedges and rice fields, with rats moving from the houses to the rice fields. During the high plague transmission season, rats moved from the hedges of sisal to the rice fields. Important indicators of vector abundance and plague transmission were higher during the high plague transmission season. The three study habitats were the risk areas for plague transmission, but the risk appeared highest in the houses and sisals. Rats' movements according to the season were likely directed by the availability of food.

  10. Rodent and flea abundance fail to predict a plague epizootic in black-tailed prairie dogs.

    Science.gov (United States)

    Brinkerhoff, Robert Jory; Collinge, Sharon K; Ray, Chris; Gage, Ken L

    2010-01-01

    Small rodents are purported to be enzootic hosts of Yersinia pestis and may serve as sources of infection to prairie dogs or other epizootic hosts by direct or flea-mediated transmission. Recent research has shown that small rodent species composition and small rodent flea assemblages are influenced by the presence of prairie dogs, with higher relative abundance of both small rodents and fleas at prairie dog colony sites compared to grasslands without prairie dogs. However, it is unclear if increased rodent or flea abundance predisposes prairie dogs to infection with Y. pestis. We tracked rodent and flea occurrence for 3 years at a number of prairie dog colony sites in Boulder County, Colorado, before, during, and after a local plague epizootic to see if high rodent or flea abundance was associated with plague-affected colonies when compared to colonies that escaped infection. We found no difference in preepizootic rodent abundance or flea prevalence or abundance between plague-positive and plague-negative colonies. Further, we saw no significant before-plague/after-plague change in these metrics at either plague-positive or plague-negative sites. We did, however, find that small rodent species assemblages changed in the year following prairie dog die-offs at plague-affected colonies when compared to unaffected colonies. In light of previous research from this system that has shown that landscape features and proximity to recently plagued colonies are significant predictors of plague occurrence in prairie dogs, we suggest that landscape context is more important to local plague occurrence than are characteristics of rodent or flea species assemblages.

  11. Transmission efficiency of two flea species (Oropsylla tuberculata cynomuris and Oropsylla hirsuta) involved in plague epizootics among prairie dogs.

    Science.gov (United States)

    Wilder, Aryn P; Eisen, Rebecca J; Bearden, Scott W; Montenieri, John A; Tripp, Daniel W; Brinkerhoff, R Jory; Gage, Kenneth L; Antolin, Michael F

    2008-06-01

    Plague, caused by Yersinia pestis, is an exotic disease in North America circulating predominantly in wild populations of rodents and their fleas. Black-tailed prairie dogs (Cynomys ludovicianus) are highly susceptible to infection, often experiencing mortality of nearly all individuals in a town as a result of plague. The fleas of black-tailed prairie dogs are Oropsylla tuberculata cynomuris and Oropsylla hirsuta. We tested the efficiency of O. tuberculata cynomuris to transmit Y. pestis daily from 24 to 96 h postinfection and compared it to previously collected data for O. hirsuta. We found that O. tuberculata cynomuris has over threefold greater transmission efficiency (0.18 infected fleas transmit Y. pestis at 24 h postinfection) than O. hirsuta (0.05 fleas transmit). Using a simple model of flea-borne transmission, we combine these laboratory measurements with field data on monthly flea loads to compare the seasonal vectorial capacity of these two flea species. Coinciding with seasonal patterns of flea abundance, we find a peak in potential for flea-borne transmission in March, during high O. tuberculata cynomuris abundance, and in September-October when O. hirsuta is common. Our findings may be useful in determining the timing of insecticidal dusting to slow plague transmission in black-tailed prairie dogs.

  12. [The time course of changes in cell immunological parameters during administration of live dry plague vaccine].

    Science.gov (United States)

    Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V

    2009-08-01

    The study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all T lymphocyte subpopulations on day 14 after vaccination. These changes are most typical of a primary vaccinated cohort. The increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines produce the time-course of changes in T lymphocyte populations (subpopulations) in response to the regular administration of plague vaccine. A high immunological load in man also promotes a significant reduction in the level of B lymphocytes.

  13. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007

    National Research Council Canada - National Science Library

    Riehm, Julia M; Projahn, Michaela; Vogler, Amy J; Rajerison, Minoaerisoa; Andersen, Genevieve; Hall, Carina M; Zimmermann, Thomas; Soanandrasana, Rahelinirina; Andrianaivoarimanana, Voahangy; Straubinger, Reinhard K; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Scholz, Holger C

    2015-01-01

    .... Unfortunately, poor infrastructure makes outbreak investigations challenging. DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007...

  14. Soro ou vacina: controvérsia no controle da peste bubônica no Rio de Janeiro (1899-1901 = Serum or vaccine: controversy in the control of the bubonic plague in Rio de Janeiro (1899-1901

    Directory of Open Access Journals (Sweden)

    Silva, Matheus Alves Duarte da

    2015-01-01

    Full Text Available O artigo analisa uma controvérsia entre Camillo Terni e Oswaldo Cruz, ocorrida no ano de 1900, em torno do controle da peste bubônica no Rio de Janeiro. Oswaldo Cruz, um dos principais líderes do recém inaugurado Instituto Soroterápico Federal, defendia que o soro antipestoso era o produto a ser utilizado para tratar as vítimas de peste e também para imunizar a população, processo conhecido como soro-vacinação. Camillo Terni, diretor do Laboratório Bacteriológico de Messina, na Itália, e enviado ao Brasil para estudar a doença, ao contrário, defendia que o soro era ineficaz e que a principal estratégia para controlar a doença deveria ser vacinar a população, propagandeando o seu método de preparação da vacina antipestosa. O embate entre os dois foi veiculado na imprensa leiga e especializada e acabou vencido por Oswaldo Cruz, pois o soro tornou-se a principal arma contra a peste e a vacina antipestosa utilizada no Rio de Janeiro não foi a de Terni, mas uma versão modificada daquela criada originalmente pela Comissão Alemã enviada à Índia. O presente artigo investiga como essa vitória foi construída, acompanhando os passos de Terni e de sua vacina no Brasil e as alianças e traduções de interesse que ele e Oswaldo Cruz efetuaram de modo a vencer o debate. Dessa forma, o artigo pretende lançar luzes sobre um capítulo pouco conhecido da história do Instituto Soroterápico Federal

  15. AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

    Science.gov (United States)

    Tollenaere, C; Duplantier, J-M; Rahalison, L; Ranjalahy, M; Brouat, C

    2011-03-01

    The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

  16. Recombinant raccoon pox vaccine protects mice against lethal plague

    Science.gov (United States)

    Osorio, J.E.; Powell, T.D.; Frank, R.S.; Moss, K.; Haanes, E.J.; Smith, S.R.; Rocke, T.E.; Stinchcomb, D.T.

    2003-01-01

    Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7??104LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague. ?? 2002 Elsevier Science Ltd. All rights reserved.

  17. Assessing plague risk and presence through surveys of small mammal flea communities

    Science.gov (United States)

    M. M. Friggens; P. L. Ford; R. R. Parmenter; M. Boyden; K. Gage

    2011-01-01

    Plague, caused by the bacterium Yersinia pestis, remains a threat to human and wildlife populations in the Western United States (Gage and Kosoy 2005). Several rodent species have been implicated as important maintenance hosts in the U.S., including Peromyscus maniculatus and Dipodomys spp. Fleas are a critical component of plague foci (Gage and Kosoy 2005)....

  18. Pattern and spatial distribution of plague in Lushoto, north-eastern ...

    African Journals Online (AJOL)

    A review of plague records from 1986 to 2002 and household interviews were carried out in the plague endemic villages to establish a pattern and spatial distribution of the disease in Lushoto district, Tanzania. Spatial data of households and village centres were collected and mapped using a hand held Global Positioning ...

  19. A plague epizootic in the black-tailed prairie dog (Cynomys ludovicianus).

    Science.gov (United States)

    Pauli, Jonathan N; Buskirk, Steven W; Williams, Elizabeth S; Edwards, William H

    2006-01-01

    Plague is the primary cause for the rangewide decline in prairie dog (Cynomys spp.) distribution and abundance, yet our knowledge of plague dynamics in prairie dog populations is limited. Our understanding of the effects of plague on the most widespread species, the black-tailed prairie dog (C. ludovicianus), is particularly weak. During a study on the population biology of black-tailed prairie dogs in Wyoming, USA, plague was detected in a colony under intensive monitoring, providing a unique opportunity to quantify various consequences of plague. The epizootic reduced juvenile abundance by 96% and adult abundance by 95%. Of the survivors, eight of nine adults and one of eight juveniles developed antibodies to Yersinia pestis. Demographic groups appeared equally susceptible to infection, and age structure was unaffected. Survivors occupied three small coteries and exhibited improved body condition, but increased flea infestation compared to a neighboring, uninfected colony. Black-tailed prairie dogs are capable of surviving a plague epizootic and reorganizing into apparently functional coteries. Surviving prairie dogs may be critical in the repopulation of plague-decimated colonies and, ultimately, the evolution of plague resistance.

  20. Population genetic structure of the prairie dog flea and plague vector, Oropsylla hirsuta.

    Science.gov (United States)

    Brinkerhoff, R Jory; Martin, Andrew P; Jones, Ryan T; Collinge, Sharon K

    2011-01-01

    Oropsylla hirsuta is the primary flea of the black-tailed prairie dog and is a vector of the plague bacterium, Yersinia pestis. We examined the population genetic structure of O. hirsuta fleas collected from 11 prairie dog colonies, 7 of which had experienced a plague-associated die-off in 1994. In a sample of 332 O. hirsuta collected from 226 host individuals, we detected 24 unique haplotype sequences in a 480 nucleotide segment of the cytochrome oxidase II gene. We found significant overall population structure but we did not detect a signal of isolation by distance, suggesting that O. hirsuta may be able to disperse relatively quickly at the scale of this study. All 7 colonies that were recently decimated by plague showed signs of recent population expansion, whereas 3 of the 4 plague-negative colonies showed haplotype patterns consistent with stable populations. These results suggest that O. hirsuta populations are affected by plague-induced prairie dog die-offs and that flea dispersal among prairie dog colonies may not be dependent exclusively on dispersal of prairie dogs. Re-colonization following plague events from plague-free refugia may allow for rapid flea population expansion following plague epizootics.

  1. Duck plague epizootics in the United States, 1967-1995

    Science.gov (United States)

    Converse, K.A.; Kidd, Gregory A.

    2001-01-01

    In 1967, the first confirmed diagnosis of duck plague (DP) in the USA was made from pekin ducks (Anas platyrhynchos domesticus) on commercial duck farms on Long Island, New York. Within 10 mo, DP was confirmed as the cause of death in migratory waterfowl on a Long Island bay. This paper reviews 120 DP epizootics reported from 1967 to 1995 that involved waterfowl species native to North America or were reported in areas with free-flying waterfowl at risk. Duck plague epizootics occurred in 21 states with the greatest number reported in Maryland (29), New York (18), California (16), and Pennsylvania (13). The greatest frequency of epizootics (86%) was detected during the months of March to June. At least 40 waterfowl species were affected with the highest frequency of epizootics reported in captive or captive-reared ducks including muscovy ducks (Cairina moschata) (68%), mallard ducks (A. platyrhynchos) (18%) and black ducks (A. rubripes) (14%). The greatest number of waterfowl died in three epizootics that involved primarily migratory birds in 1967 and 1994 in New York (USA) and 1973 in South Dakota (USA). The greatest number of DP epizootics reported since 1967 appear to have involved flocks of non-migratory rather than migratory waterfowl; therefore, in our opinion it remains unknown if DP is enzootic in either non-migratory or migratory waterfowl.

  2. Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus.

    Science.gov (United States)

    Bos, Kirsten I; Herbig, Alexander; Sahl, Jason; Waglechner, Nicholas; Fourment, Mathieu; Forrest, Stephen A; Klunk, Jennifer; Schuenemann, Verena J; Poinar, Debi; Kuch, Melanie; Golding, G Brian; Dutour, Olivier; Keim, Paul; Wagner, David M; Holmes, Edward C; Krause, Johannes; Poinar, Hendrik N

    2016-01-21

    The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.

  3. [Historical and biological approaches to the study of Modern Age French plague mass burials].

    Science.gov (United States)

    Bianuccii, Raffaella; Tzortzis, Stéfan; Fornaciari, Gino; Signoli, Michel

    2010-01-01

    The "Black Death" and subsequent epidemics from 1346 to the early 18th century spread from the Caspian Sea all over Europe six hundred years after the outbreak of the Justinian plague (541-767 AD). Plague has been one of the most devastating infectious diseases that affected the humankind and has caused approximately 200 million human deaths historically. Here we describe the different approaches adopted in the study of several French putative plague mass burials dating to the Modern Age (16th-18th centuries). Through complementation of historical, archaeological and paleobiological data, ample knowledge of both the causes that favoured the spread of the Medieval plague in cities, towns and small villages and of the modification of the customary funerary practices in urban and rural areas due to plague are gained.

  4. Climate-driven introduction of the Black Death and successive plague reintroductions into Europe.

    Science.gov (United States)

    Schmid, Boris V; Büntgen, Ulf; Easterday, W Ryan; Ginzler, Christian; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr

    2015-03-10

    The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

  5. Climate-driven introduction of the Black Death and successive plague reintroductions into Europe

    Science.gov (United States)

    Büntgen, Ulf; Easterday, W. Ryan; Ginzler, Christian; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr.

    2015-01-01

    The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe. PMID:25713390

  6. East to West or West to East: Plague Spread after the Black Death

    Directory of Open Access Journals (Sweden)

    Yujun Cui

    2016-07-01

    Full Text Available The Black Death, one of the most destructive pandemics in human history, has claimed millions of lives and considerably influenced human civilization. Following the Black Death, plague outbreaks in Europe lasted for several hundred years until late the 18th century. It is generally presumed that the Black Death was caused by Yersinia pestis (Y. pestis and spread from China to Europe in one or more waves. However, because of the lack of etiological research during the medieval period and absence of a natural plague focus in Europe today, the causative agent of this pandemic and its transmission has led to long-term debate among researchers. Thus, several questions remain including whether Y. pestis actually caused the Black Death, whether a natural plague focus existed in medieval Europe and led to post-Black Death plague outbreaks, and whether the Europe plague focus played a role in the spread and evolution of Y. pestis.

  7. Biotechnology: Genetically Engineered Pathogens (The Counterproliferation Papers, Future Warfare Series No. 53)

    Science.gov (United States)

    2010-06-01

    masses of fleas carrying the bubonic plague .18 Analysis of the destructive effect of conventional biological weapons is further supported by reports...acknowledge the Imperial Japanese Army’s deliberate infection of Chinese prisoners with bubonic plague in 1940-42.”57...pestis ( plague ), Francisella tularensis (tularemia), Brucella sp. (brucellosis), and Coxiella burnetti (Q fever), are all bacterial agents that

  8. Influence of human activity patterns on epidemiology of plague in Western Usambara Mountains, Tanzania.

    Science.gov (United States)

    Hubeau, Marianne; Gulinck, Hubert; Kimaro, Didas N; Hieronimo, Proches; Meliyo, Joel

    2014-07-01

    Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs to broaden its scope and formulate new hypotheses. This study was carried out to establish relationships between the nature and the spatial extent of selected human activities on one hand, and the reported plague cases on the other hand. Three outdoor activities namely, fetching water, collecting firewood and going to the market, were selected. Through enquiries the activity patterns related to these activities were mapped in 14 villages. Standard deviation ellipses represent the extent of action spaces. Over 130 activity types were identified and listed. Of these, fetching water, collecting firewood and going to the market were used for further analysis. The results indicate a significant correlation between the plague frequency and the size of these action spaces. Different characteristics of land use and related human activities were correlated with the plague frequency at village and hamlet levels. Significant relationships were found between plague frequency and specific sources of firewood and water, and specific market places.

  9. The history of the plague and the research on the causative agent Yersinia pestis.

    Science.gov (United States)

    Zietz, Björn P; Dunkelberg, Hartmut

    2004-02-01

    The plague is an infectious bacterial disease having a high fatality rate without treatment. It has occurred in three huge pandemics since the 6th century with millions of deaths and numerous smaller epidemics and sporadic cases. Referring to specific clinical symptoms of pulmonary plague the disease became known as the Black Death. This pandemic probably originated in central Asia and began spreading westward along major trade routes. Upon the arrival in the eastern Mediterranean the disease quickly spread especially by sea traffic to Italy, Greece and France and later throughout Europe by land. Until the 18th century many European cities were frequently affected by other great plague epidemics. The worldwide spread of the third pandemic began when the plague reached Hong Kong and Canton in the year 1894. The gram-negative coccobacillus now designated as Yersinia pestis has been discovered as the causative agent of plague in this Hong Kong outbreak. In the following years the role of rats and fleas and their detailed role in the transmission of plague has been discovered and experimentally verified. Today the plague is still endemic in many countries of the world.

  10. Burrow dusting or oral vaccination prevents plague-associated prairie dog colony collapse

    Science.gov (United States)

    Tripp, Daniel W.; Rocke, Tonie E.; Runge, Jonathan P.; Abbott, Rachel C.; Miller, Michael W.

    2017-01-01

    Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant “sylvatic plague vaccine” [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots (“blocks”) receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P dogs captured on dust plots had fewer fleas (P dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

  11. Burrow Dusting or Oral Vaccination Prevents Plague-Associated Prairie Dog Colony Collapse.

    Science.gov (United States)

    Tripp, Daniel W; Rocke, Tonie E; Runge, Jonathan P; Abbott, Rachel C; Miller, Michael W

    2017-09-01

    Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant "sylvatic plague vaccine" [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots ("blocks") receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

  12. The abundance threshold for plague as a critical percolation phenomenon

    DEFF Research Database (Denmark)

    Davis, S; Trapman, P; Leirs, H

    2008-01-01

    that it is a percolation threshold, which arises from the difference in scale between the movements that transport infectious fleas between family groups and the vast size of contiguous landscapes colonized by gerbils. Conventional theory predicts that abundance thresholds for the spread of infectious disease arise when......Percolation theory is most commonly associated with the slow flow of liquid through a porous medium, with applications to the physical sciences 1 . Epidemiological applications have been anticipated for disease systems where the host is a plant or volume of soil 2, 3 , and hence is fixed in space....... However, no natural examples have been reported. The central question of interest in percolation theory 4 , the possibility of an infinite connected cluster, corresponds in infectious disease to a positive probability of an epidemic. Archived records of plague (infection with Yersinia pestis...

  13. The climatic context of major plague outbreaks in late medieval England

    Science.gov (United States)

    Pribyl, Kathleen

    2017-04-01

    The climatological triggers of major plague outbreaks in late medieval and early modern Europe remain unclear; recent studies have been inconclusive. Plague is primarily a rodent disease and due to the involvement of rodent hosts and insect vectors, the epidemiology of plague is complicated, but research on outbreaks in the Third Pandemic, which began in the late nineteenth century, has shown that in central and eastern Asia plague is linked to specific meteorological conditions. The disease adapts to a varied spectrum of ecological and climatological settings, which influence the development of plague waves, and due to Europe's geographical diversity, this paper focuses on one region, England, in its search for meteorological parameters contributing to plague outbreaks. The study period of this paper is defined by the arrival of Yersinia pestis in the British Isles in 1348 and the end of the fifteenth century. During this time, England's population dynamics were mortality-driven due to recurrent epidemic disease; and public health measures, such as quarantining, had not yet been introduced, hence the influence of social factors on the formation of major plague waves was very limited. The geographical and temporal focus of this study allows for the combination of the series of English major plague outbreaks, verified in the original texts, with the high-quality climate reconstructions based on both documentary sources and proxy data available for this region. The detailed analysis of the mechanisms contributing to English plague waves presented in this paper, reveals a complex interplay of time-lag responses and concurrent conditions involving temperature and precipitation parameters.

  14. The Stone Age Plague and Its Persistence in Eurasia.

    Science.gov (United States)

    Andrades Valtueña, Aida; Mittnik, Alissa; Key, Felix M; Haak, Wolfgang; Allmäe, Raili; Belinskij, Andrej; Daubaras, Mantas; Feldman, Michal; Jankauskas, Rimantas; Janković, Ivor; Massy, Ken; Novak, Mario; Pfrengle, Saskia; Reinhold, Sabine; Šlaus, Mario; Spyrou, Maria A; Szécsényi-Nagy, Anna; Tõrv, Mari; Hansen, Svend; Bos, Kirsten I; Stockhammer, Philipp W; Herbig, Alexander; Krause, Johannes

    2017-12-04

    Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6th century AD, which persisted until the 8th century [1]; the renowned Black Death of the 14th century [2, 3], with recurrent outbreaks until the 18th century [4]; and the most recent 19th century pandemic, in which Y. pestis spread worldwide [5] and became endemic in several regions [6]. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic [7]. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange [8, 9]. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A bibliography of literature pertaining to plague (Yersinia pestis)

    Science.gov (United States)

    Ellison, Laura E.; Frank, Megan K. Eberhardt

    2011-01-01

    Plague is an acute and often fatal zoonotic disease caused by the bacterium Yersinia pestis. Y. pestis mainly cycles between small mammals and their fleas; however, it has the potential to infect humans and frequently causes fatalities if left untreated. It is often considered a disease of the past; however, since the late 1800s, plagueis geographic range has expanded greatly, posing new threats in previously unaffected regions of the world, including the Western United States. A literature search was conducted using Internet resources and databases. The keywords chosen for the searches included plague, Yersinia pestis, management, control, wildlife, prairie dogs, fleas, North America, and mammals. Keywords were used alone or in combination with the other terms. Although this search pertains mostly to North America, citations were included from the international research community, as well. Databases and search engines used included Google (http://www.google.com), Google Scholar (http://scholar.google.com), SciVerse Scopus (http://www.scopus.com), ISI Web of Knowledge (http://apps.isiknowledge.com), and the USGS Library's Digital Desktop (http://library.usgs.gov). The literature-cited sections of manuscripts obtained from keyword searches were cross-referenced to identify additional citations or gray literature that was missed by the Internet search engines. This Open-File Report, published as an Internet-accessible bibliography, is intended to be periodically updated with new citations or older references that may have been missed during this compilation. Hence, the authors would be grateful to receive notice of any new or old papers that the audience (users) think need to be included.

  16. Plague in Egypt: Disease biology, history and contemporary analysis: A minireview

    Directory of Open Access Journals (Sweden)

    Wael M. Lotfy

    2015-07-01

    Full Text Available Plague is a zoonotic disease with a high mortality rate in humans. Unfortunately, it is still endemic in some parts of the world. Also, natural foci of the disease are still found in some countries. Thus, there may be a risk of global plague re-emergence. This work reviews plague biology, history of major outbreaks, and threats of disease re-emergence in Egypt. Based on the suspected presence of potential natural foci in the country, the global climate change, and the threat posed by some neighbouring countries disease re-emergence in Egypt should not be excluded. The country is in need for implementation of some preventive measures.

  17. Early apoptosis of macrophages modulated by injection of Yersinia pestis YopK promotes progression of primary pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Kristen N Peters

    Full Text Available Yersinia pestis causes pneumonic plague, a disease characterized by inflammation, necrosis and rapid bacterial growth which together cause acute lung congestion and lethality. The bacterial type III secretion system (T3SS injects 7 effector proteins into host cells and their combined activities are necessary to establish infection. Y. pestis infection of the lungs proceeds as a biphasic inflammatory response believed to be regulated through the control of apoptosis and pyroptosis by a single, well-conserved T3SS effector protein YopJ. Recently, YopJ-mediated pyroptosis, which proceeds via the NLRP3-inflammasome, was shown to be regulated by a second T3SS effector protein YopK in the related strain Y. pseudotuberculosis. In this work, we show that for Y. pestis, YopK appears to regulate YopJ-mediated apoptosis, rather than pyroptosis, of macrophages. Inhibition of caspase-8 blocked YopK-dependent apoptosis, suggesting the involvement of the extrinsic pathway, and appeared cell-type specific. However, in contrast to yopJ, deletion of yopK caused a large decrease in virulence in a mouse pneumonic plague model. YopK-dependent modulation of macrophage apoptosis was observed at 6 and 24 hours post-infection (HPI. When YopK was absent, decreased populations of macrophages and dendritic cells were seen in the lungs at 24 HPI and correlated with resolution rather than progression of inflammation. Together the data suggest that Y. pestis YopK may coordinate the inflammatory response during pneumonic plague through the regulation of apoptosis of immune cells.

  18. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007: e0003844

    National Research Council Canada - National Science Library

    Julia M Riehm; Michaela Projahn; Amy J Vogler; Minoaerisoa Rajerison; Genevieve Andersen; Carina M Hall; Thomas Zimmermann; Rahelinirina Soanandrasana; Voahangy Andrianaivoarimanana; Reinhard K Straubinger; Roxanne Nottingham; Paul Keim; David M Wagner; Holger C Scholz

    2015-01-01

    .... Unfortunately, poor infrastructure makes outbreak investigations challenging. Methodology/Principal Findings DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007...

  19. [The plague: A disease that is still haunting our collective memory].

    Science.gov (United States)

    Peiffer-Smadja, N; Thomas, M

    2017-06-01

    Although the plague has practically disappeared from Europe since the beginning of the 20th century, it is still present in everyone's memory. Owing to three pandemics, it has left an indelible mark on mankind and has given rise to many popular phrases, paintings, books or more recently movies and video games. After a brief description of the plague as a disease, we will try to trace the history of the plague through some of the works of art it inspired and then to show how the plague is still haunting our collective memory. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  20. Epidemiology of Human Plague in the United States, 1900–2012

    Centers for Disease Control (CDC) Podcasts

    2015-02-23

    Dr. Kiersten Kugeler discusses the Epidemiology of Human Plague in the United States.  Created: 2/23/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 2/23/2015.

  1. No evidence of deer mouse involvement in plague (Yersinia pestis) epizootics in prairie dogs.

    Science.gov (United States)

    Salkeld, Daniel J; Stapp, Paul

    2008-06-01

    Plague, the disease caused by the bacterium Yersinia pestis, can have devastating impacts on black-tailed prairie dog (Cynomys ludovicianus) colonies. One suggested mechanism behind sporadic prairie dog die-offs involves an alternative mammal host, such as the deer mouse (Peromyscus maniculatus), which often inhabits prairie dog colonies. We examined the flea populations of deer mice to investigate the potential of flea-borne transmission of plague between deer mice and prairie dogs in northern Colorado, where plague is active in prairie dog colonies. Deer mice were predominantly infested with the flea Aetheca wagneri, and were rarely infested with prairie dog fleas, Oropsylla hirsuta. Likelihood of flea infestation increased with average monthly temperature, and flea loads were higher in reproductive animals. These results suggest that the deer mouse is an unlikely maintenance host of plague in this region.

  2. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007

    OpenAIRE

    Riehm, Julia M.; Michaela Projahn; Vogler, Amy J; Minoaerisoa Rajerison; Genevieve Andersen; Hall, Carina M.; Thomas Zimmermann; Rahelinirina Soanandrasana; Voahangy Andrianaivoarimanana; Straubinger, Reinhard K.; Roxanne Nottingham; Paul Keim; David M Wagner; Scholz, Holger C

    2015-01-01

    International audience; BackgroundYersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging. Methodology/Principal FindingsDNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007....

  3. A Field Study of Plague and Tularemia in Rodents, Western Iran.

    Science.gov (United States)

    Mostafavi, Ehsan; Shahraki, Abdolrazagh Hashemi; Japoni-Nejad, Alireza; Esmaeili, Saber; Darvish, Jamshid; Sedaghat, Mohammad Mehdi; Mohammadi, Ali; Mohammadi, Zeinolabedin; Mahmoudi, Ahmad; Pourhossein, Behzad; Ghasemi, Ahmad; Gyuranecz, Miklós; Carniel, Elisabeth

    2017-04-01

    Kurdistan Province in Iran is a historical focus for plague and tularemia. This study aimed at assessing the current status of these two foci by studying their rodent reservoirs. Rodents were trapped and their ectoparasites were collected. The genus and species of both rodents and ectoparasites were determined. Serological analyses of rodent blood samples were done by enzyme-linked immunosorbent assay for plague and by standard tube agglutination assay for tularemia. Rodent spleen samples were subjected to bacterial culture, microscopic examination, and real-time PCR to search for active plague or tularemia infection. During this study, 245 rodents were trapped, of which the most abundant genera were Apodemus (40%), Mus (24.49%), and Meriones (12.65%). One hundred fifty-three fleas, 37 mites, and 54 ticks were collected on these rodents. The results of all direct and indirect tests were negative for plague. Serological tests were positive for tularemia in 4.8% of trapped rodents. This study is the first report on the presence of tularemia infection in rodents in Western Iran. Since Meriones persicus is a known reservoir for plague and tularemia, and this rodent carried plague and tularemia vectors in Marivan and Sanandaj districts, there is a real potential for the occurrence of these two diseases in this region.

  4. Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania.

    Science.gov (United States)

    Hieronimo, Proches; Gulinck, Hubert; Kimaro, Didas N; Mulungu, Loth S; Kihupi, Nganga I; Msanya, Balthazar M; Leirs, Herwig; Deckers, Jozef A

    2014-07-01

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto District. Data were collected in three landscapes differing in plague incidence. Field survey coupled with Geographic Information System (GIS) and physical sample collections were used to collect data in wet (April to June 2012) and dry (August to October 2012) seasons. Data analysis was done using GIS, one-way ANOVA and nonparametric statistical tools. The degree of spatial co-occurrence of potential disease vectors (fleas) and humans in Lushoto focus differs significantly (p ≤ 0.05) among the selected landscapes, and in both seasons. This trend gives a coarse indication of the possible association of the plague outbreaks and the human frequencies of contacting environments with fleas. The study suggests that plague surveillance and control programmes at landscape scale should consider the existence of plague vector contagion risk gradient from high to low incidence landscapes due to human presence and intensity of activities.

  5. Small mammal distribution and diversity in a plague endemic area in West Usambara Mountains, Tanzania.

    Science.gov (United States)

    Ralaizafisoloarivony, Njaka A; Kimaro, Didas N; Kihupi, Nganga I; Mulungu, Loth S; Leirs, Herwig; Msanya, Balthazar M; Deckers, Jozef A; Gulinck, Hubert

    2014-07-01

    Small mammals play a role in plague transmission as hosts in all plague endemic areas. Information on distribution and diversity of small mammals is therefore important for plague surveillance and control in such areas. The objective of this study was to investigate small mammals' diversity and their distribution in plague endemic area in the West Usambara Mountains in north-eastern Tanzania. Landsat images and field surveys were used to select trapping locations in different landscapes. Three landscapes with different habitats were selected for trapping of small mammals. Three types of trap were used in order to maximise the number of species captured. In total, 188 animals and thirteen species were captured in 4,905 trap nights. Praomys delectorum and Mastomys natalensis both reported as plague hosts comprised 50% of all the animals trapped. Trap success increased with altitude. Species diversity was higher in plantation forest followed by shrub, compared to other habitats, regardless of landscape type. It would therefore seem that chances of plague transmission from small mammals to humans are much higher under shrub, natural and plantation forest habitats.

  6. [The North African plague and Charles Nicolle's theory of infectious diseases].

    Science.gov (United States)

    Ben, Néfissa Kmar; Moulin, Anne Marie

    2010-01-01

    Many infectious diseases were described in North Africa in 18th-19th centuries by European travellers. Most of them were allegedly imported by new migrant populations coming from sub-Saharan, European or Middle East countries. Plague outbreaks have been described since the Black Death as diseases of the Mediterranean harbours. Charles Nicolle and his collaborators at the Pasteur Institute were witnesses to the extinction of plague and typhus fever in Tunisia. Both could be considered as endemo-epidemic diseases propagated by ancient nomad communities for centuries. Typhus was exported to other countries; plague was imported by Mediterranean travellers but also hid in unknown wild-animal reservoirs. The role of the bite of a rat's flea was not confirmed and the pneumonic form might have prevailed in the medieval North African cities. Association between plague, typhus, flu and other causes of immune deficiencies could explain the high morbidity and mortality caused by plague in the past. The authors comment the local history of plague at the light of the evolutionary laws of infectious disease proposed by Charles Nicolle in 1930.

  7. Comparative genomics of 2009 seasonal plague (Yersinia pestis in New Mexico.

    Directory of Open Access Journals (Sweden)

    Henry S Gibbons

    Full Text Available Plague disease caused by the gram-negative bacterium Yersinia pestis routinely affects animals and occasionally humans, in the western United States. The strains native to the North American continent are thought to be derived from a single introduction in the late 19(th century. The degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of North American plague are highly desired. To assay genetic diversity of plague isolates within confined geographic areas, draft genome sequences were generated by 454 pyrosequencing from nine environmental and clinical plague isolates. In silico assemblies of Variable Number Tandem Repeat (VNTR loci were compared to laboratory-generated profiles for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels were compared to previously sequenced Y. pestis isolates. The resulting panel of mutations allowed clustering of the strains and tracing of the most likely evolutionary trajectory of the plague strains. The sequences also allowed the identification of new putative SNPs that differentiate the 2009 isolates from previously sequenced plague strains and from each other. In addition, new insertion points for the abundant insertion sequences (IS of Y. pestis are present that allow additional discrimination of strains; several of these new insertions potentially inactivate genes implicated in virulence. These sequences enable whole-genome phylogenetic analysis and allow the unbiased comparison of closely related isolates of a genetically monomorphic pathogen.

  8. Flea abundance on black-tailed prairie dogs (Cynomys ludovicianus) increases during plague epizootics.

    Science.gov (United States)

    Tripp, Daniel W; Gage, Kenneth L; Montenieri, John A; Antolin, Michael F

    2009-06-01

    Black-tailed prairie dogs (Cynomys ludovicianus) on the Great Plains of the United States are highly susceptible to plague, caused by the bacterium Yersinia pestis, with mortality on towns during plague epizootics often approaching 100%. The ability of flea-borne transmission to sustain disease spread has been questioned because of inefficiency of flea vectors. However, even with low individual efficiency, overall transmission can be increased if flea abundance (the number of fleas on hosts) increases. Changes in flea abundance on hosts during plague outbreaks were recorded during a large-scale study of plague outbreaks in prairie dogs in north central Colorado during 3 years (2004-2007). Fleas were collected from live-trapped black-tailed prairie dogs before and during plague epizootics and tested by PCR for the presence of Y. pestis. The predominant fleas were two prairie dog specialists (Oropsylla hirsuta and Oropsylla tuberculata cynomuris), and a generalist flea species (Pulex simulans) was also recorded from numerous mammals in the area. The three species differ in seasonal abundance, with greatest abundance in spring (February and March) and fall (September and October). Flea abundance and infestation intensity increased during epizootics and were highest on prairie dogs with Y. pestis-infected fleas. Seasonal occurrence of epizootics among black-tailed prairie dogs was found to coincide with seasonal peaks in flea abundance. Concentration of infected fleas on surviving animals may account for rapid spread of plague during epizootics. In particular, the role of the generalist flea P. simulans was previously underappreciated.

  9. Efficacy and activity prediction by molecular topology of new drugs against the Tetranychus urticae plague.

    Science.gov (United States)

    Mérida, Salvador; Fustero, Santos; Villar, Vincent M; Gálvez, María; Román, Raquel; Amigó, José M

    2013-07-01

    Tetranychus urticae Koch is an important pest affecting citrus, for which biological control has not yet been achieved; therefore, acaricides are commonly used instead. The goal of the work reported in this paper was to measure the efficacy of different new compounds--uracil derivatives--on this mite and conduct a quantitative structure-activity relationship (QSAR) study based on the results obtained, in order to set up a model capable of predicting the acaricidal activity of further new compounds. Some of the tested new products proved highly effective against T. urticae. Besides, topological indices were used as structural descriptors. The result was a topological model consisting of two discriminant functions for distinguishing between active and inactive compounds, and a predictive equation for the adult mortality percentage on the sixth day. This model was then sequentially applied to a large database of compounds with unknown activity against the Tetranychus urticae plague. Finally, a preliminary toxicity study of the most effective novel compounds supports their non-toxicity, performing even better than commercial referents.

  10. Potential role of viruses in white plague coral disease.

    Science.gov (United States)

    Soffer, Nitzan; Brandt, Marilyn E; Correa, Adrienne M S; Smith, Tyler B; Thurber, Rebecca Vega

    2014-02-01

    White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.

  11. Duration of plague (Yersinia pestis) outbreaks in black-tailed prairie dog (Cynomys ludovicianus) colonies of northern Colorado.

    Science.gov (United States)

    St Romain, Krista; Tripp, Daniel W; Salkeld, Daniel J; Antolin, Michael F

    2013-09-01

    Plague, caused by the bacterium Yersinia pestis, triggers die-offs in colonies of black-tailed prairie dogs (Cynomys ludovicianus), but the time-frame of plague activity is not well understood. We document plague activity in fleas from prairie dogs and their burrows on three prairie dog colonies that suffered die-offs. We demonstrate that Y. pestis transmission occurs over periods from several months to over a year in prairie dog populations before observed die-offs.

  12. Oropsylla hirsuta (Siphonaptera: Ceratophyllidae) can support plague epizootics in black-tailed prairie dogs (Cynomys ludovicianus) by early-phase transmission of Yersinia pestis.

    Science.gov (United States)

    Wilder, Aryn P; Eisen, Rebecca J; Bearden, Scott W; Montenieri, John A; Gage, Kenneth L; Antolin, Michael F

    2008-06-01

    Plague, caused by the bacterium Yersinia pestis, often leads to rapid decimation of black-tailed prairie dog colonies. Flea-borne transmission of Y. pestis has been thought to occur primarily via blocked fleas, and therefore studies of vector efficiency have focused on the period when blockage is expected to occur (> or =5 days post-infection [p.i.]). Oropsylla hirsuta, a prairie dog flea, rarely blocks and transmission is inefficient > or =5 days p.i.; thus, this flea has been considered incapable of explaining rapid dissemination of Y. pestis among prairie dogs. By infecting wild-caught fleas with Y. pestis and exposing naïve mice to groups of fleas at 24, 48, 72, and 96 h p.i., we examined the early-phase (1-4 days p.i.) efficiency of O. hirsuta to transmit Y. pestis to hosts and showed that O. hirsuta is a considerably more efficient vector at this largely overlooked stage (5.19% of fleas transmit Y. pestis at 24 h p.i.) than at later stages. Using a model of vectorial capacity, we suggest that this level of transmission can support plague at an enzootic level in a population when flea loads are within the average observed for black-tailed prairie dogs in nature. Shared burrows and sociality of prairie dogs could lead to accumulation of fleas when host population is reduced as a result of the disease, enabling epizootic spread of plague among prairie dogs.

  13. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs.

    Science.gov (United States)

    Busch, Joseph D; Van Andel, Roger; Stone, Nathan E; Cobble, Kacy R; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William; Shuey, Megan M; Foster, Jeffrey T; Schupp, James M; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L; Rocke, Tonie E; Wagner, David M

    2013-10-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  14. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Stone, Nathan E.; Cobble, Kacy R.; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William E.; Shuey, Megan M.; Foster, Jeffrey T.; Schupp, James M.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L.; Rocke, Tonie E.; Wagner, David M.

    2013-01-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  15. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Directory of Open Access Journals (Sweden)

    Voahangy Andrianaivoarimanana

    Full Text Available Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci.We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks.Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  16. Sylvatic plague vaccine partially protects prairie dogs (Cynomys spp.) in field trials

    Science.gov (United States)

    Rocke, Tonie E.; Tripp, Daniel W.; Russell, Robin E.; Abbott, Rachel C.; Richgels, Katherine; Matchett, Marc R.; Biggins, Dean E.; Griebel, Randall; Schroeder, Greg; Grassel, Shaun M.; Pipkin, David R.; Cordova, Jennifer; Kavalunas, Adam; Maxfield, Brian; Boulerice, Jesse; Miller, Michael W.

    2017-01-01

    Sylvatic plague, caused by Yersinia pestis, frequently afflicts prairie dogs (Cynomys spp.), causing population declines and local extirpations. We tested the effectiveness of bait-delivered sylvatic plague vaccine (SPV) in prairie dog colonies on 29 paired placebo and treatment plots (1–59 ha in size; average 16.9 ha) in 7 western states from 2013 to 2015. We compared relative abundance (using catch per unit effort (CPUE) as an index) and apparent survival of prairie dogs on 26 of the 29 paired plots, 12 with confirmed or suspected plague (Y. pestis positive carcasses or fleas). Even though plague mortality occurred in prairie dogs on vaccine plots, SPV treatment had an overall positive effect on CPUE in all three years, regardless of plague status. Odds of capturing a unique animal were 1.10 (95% confidence interval [C.I.] 1.02–1.19) times higher per trap day on vaccine-treated plots than placebo plots in 2013, 1.47 (95% C.I. 1.41–1.52) times higher in 2014 and 1.19 (95% C.I. 1.13–1.25) times higher in 2015. On pairs where plague occurred, odds of apparent survival were 1.76 (95% Bayesian credible interval [B.C.I.] 1.28–2.43) times higher on vaccine plots than placebo plots for adults and 2.41 (95% B.C.I. 1.72–3.38) times higher for juveniles. Our results provide evidence that consumption of vaccine-laden baits can protect prairie dogs against plague; however, further evaluation and refinement are needed to optimize SPV use as a management tool.

  17. Construction and screening of attenuated ΔphoP/Q Salmonella typhimurium vectored plague vaccine candidates.

    Science.gov (United States)

    Sizemore, Donata R; Warner, Elizabeth A; Lawrence, Julie A; Thomas, Lawrence J; Roland, Kenneth L; Killeen, Kevin P

    2012-03-01

    Preclinical studies evaluating plague vaccine candidates have demonstrated that the F1 and V protein antigens of Yersinia pestis confer protection against challenge from virulent strains. Live-attenuated ΔphoP/Q Salmonella typhimurium recombinants were constructed expressing either F1, V antigens, F1 and V antigens, or a F1-V fusion from Asd (+) balanced-lethal plasmids. To improve antigen delivery, genes encoding plague antigens were modified in order to localize antigens to specific bacterial cellular compartments which include cytoplasmic, outer membrane, or secreted. Candidate vaccine strains were evaluated for growth characteristics, full-length lipopolysaccharide (LPS), plasmid stability, and antigen expression in vitro. Plague vaccine candidate strains with favorable in vitro profiles were evaluated in murine or rabbit preclinical oral immunogenicity studies. Attenuated S. typhimurium strains expressing cytoplasmically localized F1-V and V antigen antigens were more immunogenic than strains that secreted or localized plague antigens to the outer membrane. In particular, S. typhimurium M020 and M023, which express Asd(+)-plasmid derived soluble F1-V and soluble V antigen, respectively, at high levels in the bacterial cell cytoplasm were found to induce the highest levels of plague-specific serum antibodies. To further evaluate balanced-lethal plasmid retention capacity, ΔphoP/Q S. typhimurium PurB(+) and GlnA(+) balanced-lethal plasmid systems harboring F1-V were compared with M020 in vitro and in BALB/c mice in a immunogenicity study. Although there was no detectable difference in plague antigen expression in vitro, S. typhimurium M020 was the most immunogenic plague antigen vector strain evaluated, inducing high-titer serum IgG antibodies specific against F1, V and F1-V.

  18. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    Science.gov (United States)

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  19. Opposing roles for interferon regulatory factor-3 (IRF-3 and type I interferon signaling during plague.

    Directory of Open Access Journals (Sweden)

    Ami A Patel

    Full Text Available Type I interferons (IFN-I broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

  20. Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia

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    Hang'ombe Bernard M

    2012-01-01

    Full Text Available Abstract Background Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. Findings Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02% for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. Conclusions We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia.

  1. Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

    Directory of Open Access Journals (Sweden)

    Adélaïde Miarinjara

    2016-02-01

    Full Text Available Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines. Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur. Only one insecticide (dieldrin was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

  2. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007.

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    Julia M Riehm

    2015-06-01

    Full Text Available Yersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging.DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007. The extracted DNAs were then genotyped using three molecular genotyping methods, including, single nucleotide polymorphism (SNP typing, multi-locus variable-number tandem repeat analysis (MLVA, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR analysis. These methods provided increasing resolution, respectively. The results of these analyses revealed that, in 2007, ten molecular groups, two newly described here and eight previously identified, were responsible for causing human plague in geographically distinct areas of Madagascar.Plague in Madagascar is caused by numerous distinct types of Y. pestis. Genotyping method choice should be based upon the discriminatory power needed, expense, and available data for any desired comparisons. We conclude that genotyping should be a standard tool used in epidemiological investigations of plague outbreaks.

  3. [Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010].

    Science.gov (United States)

    Donaires, Luis F; Céspedes, Manuel; Valencia, Pedro; Salas, Juan Carlos; Luna, María E; Castañeda, Alex; Peralta, Víctor; Cabezas, César; Pachas, Paul E

    2010-09-01

    Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4). Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

  4. Gene flow in a Yersinia pestis vector, Oropsylla hirsuta, during a plague epizootic.

    Science.gov (United States)

    Jones, Philip H; Washburn, Leigh R; Britten, Hugh B

    2011-09-01

    Appreciating how Yersinia pestis, the etiological agent of plague, spreads among black - tailed prairie dog (Cynomys ludovicianus) colonies (BTPD), is vital to wildlife conservation programs in North American grasslands. A little - studied aspect of the system is the role of Y. pestis vectors, i.e. fleas, play in the spreading of plague in natural settings. We investigated the genetic structure and variability of a common prairie dog flea (Oropsylla hirsuta) in BTPD colonies in order to examine dispersal patterns. Given that this research took place during a widespread plague epizootic, there was the added advantage of gaining information on the dynamics of sylvatic plague. Oropsylla hirsuta were collected from BTPD burrows in nine colonies from May 2005 to July 2005, and eight polymorphic microsatellite markers were used to generate genotypic data from them. Gene flow estimates revealed low genetic differentiation among fleas sampled from different colonies. NestedPCR plague assays confirmed the presence of Y. pestis with the average Y. pestis prevalence across all nine colonies at 12%. No significant correlations were found between the genetic variability and gene flow of O. hirsuta and Y. pestis prevalence on a per -colony basis. Oropsylla hirsuta dispersal among BTPD colonies was high, potentially explaining the rapid spread of Y. pestis in our study area in 2005 and 2006.

  5. Sylvatic plague reduces genetic variability in black-tailed prairie dogs.

    Science.gov (United States)

    Trudeau, Kristie M; Britten, Hugh B; Restani, Marco

    2004-04-01

    Small, isolated populations are vulnerable to loss of genetic diversity through in-breeding and genetic drift. Sylvatic plague due to infection by the bacterium Yersinia pestis caused an epizootic in the early 1990s resullting in declines and extirpations of many black-tailed prairie dog (Cynomys ludovicianus) colonies in north-central Montana, USA. Plague-induced population bottlenecks may contribute to significant reductions in genetic variability. In contrast, gene flow maintains genetic variability within colonies. We investigated the impacts of the plague epizootic and distance to nearest colony on levels of genetic variability in six prairie dog colonies sampled between June 1999 and July 2001 using 24 variable randomly amplified polymorphic DNA (RAPD) markers. Number of effective alleles per locus (n(e)) and gene diversity (h) were significantly decreased in the three colonies affected by plague that were recovering from the resulting bottlenecks compared with the three colonies that did not experience plague. Genetic variability was not significantly affected by geographic distance between colonies. The majority of variance in gene fieqnencies was found within prairie clog colonies. Conservation of genetic variability in black-tailed prairie dogs will require the preservation of both large and small colony complexes and the gene flow amonog them.

  6. Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

    Science.gov (United States)

    Miarinjara, Adélaïde; Boyer, Sébastien

    2016-02-01

    Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

  7. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007.

    Science.gov (United States)

    Riehm, Julia M; Projahn, Michaela; Vogler, Amy J; Rajerison, Minoaerisoa; Andersen, Genevieve; Hall, Carina M; Zimmermann, Thomas; Soanandrasana, Rahelinirina; Andrianaivoarimanana, Voahangy; Straubinger, Reinhard K; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Scholz, Holger C

    2015-06-01

    Yersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging. DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007. The extracted DNAs were then genotyped using three molecular genotyping methods, including, single nucleotide polymorphism (SNP) typing, multi-locus variable-number tandem repeat analysis (MLVA), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) analysis. These methods provided increasing resolution, respectively. The results of these analyses revealed that, in 2007, ten molecular groups, two newly described here and eight previously identified, were responsible for causing human plague in geographically distinct areas of Madagascar. Plague in Madagascar is caused by numerous distinct types of Y. pestis. Genotyping method choice should be based upon the discriminatory power needed, expense, and available data for any desired comparisons. We conclude that genotyping should be a standard tool used in epidemiological investigations of plague outbreaks.

  8. Two medieval plague treatises and their afterlife in early modern England.

    Science.gov (United States)

    Keiser, George R

    2003-07-01

    This study of an adaptation of the popular John of Burgundy plague treatise by Thomas Moulton, a Dominican friar, ca. 1475, and a translation of the so-called Canutus plague treatise by Thomas Paynell, printed 1534, shows how the medieval traditions they represent were carried forward, well into the sixteenth century, and also subjected to change in light of religious, moral, and medical concerns of early modern England. The former had a long life in print, ca. 1530-1580, whereas Paynell's translation exists in one printed version. Moulton's adaptation differs from its original and from the Canutus treatise in putting great emphasis on the idea that onsets of plague were acts of divine retribution for human sinfulness. In this respect, Moulton reshaped the tradition of the medieval plague treatise and anticipated the religious and social construction of plague that would take shape in the first half of the sixteenth century. Its long history in print indicates that Moulton's treatise expressed the spirit of that construction and probably influenced the construction as well. The contrasting histories of the two treatises attest not only to the dramatic change brought about by religious and social forces in the sixteenth century, but to a growing recognition of the value of the printing press for disseminating medical information-in forms that served social and ideological ends.

  9. Napoleon’s Missed Opportunities to Maintain Combat Forces through Medical Innovations and Battling the Hidden Enemy

    Science.gov (United States)

    2011-12-07

    different countries resulted in baffling new challenges for Napoleon’s doctors. Firstly during the Egyptian campaign in 1798 and 1799, bubonic plague swept...the bubonic plague but were based on the wrong etiology. Plague is caused by a bacterium called Yersenia pestis and is transmitted from rodent- to... Plague Napoleon’s Forces Despite living in an era with incessant conflict, Napoleon’s forces were more likely to succumb to disease than meet a

  10. [A NATURAL PLAGUE FOCUS. IN GORNYI ALTAI: FORMATION, DEVELOPMENT, AND FUNCTIONING].

    Science.gov (United States)

    Korzun, V M; Balakhoiov, S V; Chpanin, E V; Denisov, A V; Mikhailov, E P; Mischenko, A J; Yarygina, M B; Rozhdestvensky, E N; Fomina, L A

    2016-01-01

    The paper gives the results of analyzing the data of long-term studies of the natural focal pattern of plague in the Gornyi Altai natural focus. It describes a wide range of biological processes occurring in the focus and shows the most important patterns of its functioning as a complex multilevel ecological system. The key features of the formation of the focus have been revealed. The plague focus in South-Western Altai has formed relatively, recently, about half a century ago, then it has intensively developed and its enzootic area and the activity of epizootic manifestations have considerably increased. This process is due to the space-time transformations of the basic ecological and population characteristics of Pallas' pika (Ochotoma pallasi), the principal vector of the pathogen of plague and fleas parasitizing the mammal, which is in turn related to the aridization of mountain steppes in South-Western Altai.

  11. Further development of raccoon poxvirus-vectored vaccines against plague (Yersinia pestis)

    Science.gov (United States)

    Rocke, T.E.; Iams, Keith P.; Dawe, S.; Smith, S.R.; Williamson, J.L.; Heisey, D.M.; Osorio, J.E.

    2009-01-01

    In previous studies, we demonstrated protection against plague in mice and prairie dogs using a raccoon pox (RCN) virus-vectored vaccine that expressed the F1 capsular antigen of Yersinia pestis. In order to improve vaccine efficacy, we have now constructed additional RCN-plague vaccines containing two different forms of the lcrV (V) gene, including full-length (Vfull) and a truncated form (V307). Mouse challenge studies with Y. pestis strain CO92 showed that vaccination with a combination of RCN-F1 and the truncated V construct (RCN-V307) provided the greatest improvement (P = 0.01) in protection against plague over vaccination with RCN-F1 alone. This effect was mediated primarily by anti-F1 and anti-V antibodies and both contributed independently to increased survival of vaccinated mice.

  12. Findings of bacterial microflora in piglets infected with conventional swine plague

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    Prodanov Jasna

    2002-01-01

    Full Text Available Piglets infected with the conventional swine plague virus as a result of secondary bacterial infections sometimes show an insufficiently clear clinical and pathoanatomical picture, which is why the very procedure of diagnosis is complex and the final diagnosis unreliable. That is why these investigations were aimed at examining the presence of bacterial microflora in diseased and dead pilgets which were found to have the viral antigen for CSP using the fluorescent antibody technique, in cases where the pathomorphological finding was not characteristic for conventional swine plague. Autopsies of dead piglets most often showed changes in the digestive tract and lungs, with resulting technopathy and diseases of infective nature. Such findings on knowledge of a present bacterial microflora are especially important in cases when conventional swine plague is controlled on farms and an announcement that the disease has been contained is in the offing.

  13. Seroprevalence of hantavirus and Yersinia pestis antibodies in professionals from the Plague Control Program

    Directory of Open Access Journals (Sweden)

    Erika de Cassia Vieira da Costa

    2013-07-01

    Full Text Available Introduction Professionals who handle rodents in the field and in the laboratory are at risk of infection by the microorganisms harbored by these animals. Methods Serum samples from professionals involved in rodent and Yersinia pestis handling in field or laboratory work were analyzed to determine hantavirus and plague seroprevalence and to establish a relationship between these activities and reports of illnesses. Results Two individuals had antibodies against hantavirus, and two harbored antibodies against the plague; none of the individuals had experienced an illness related to their duties. Conclusions These results confirm the risks of hantavirus- and plague-related field and laboratory activities and the importance of protective measures for such work.

  14. 275 years since the epidemic of plague in Cluj: Dr. Alexandru Lenghel's contribution to its investigation.

    Science.gov (United States)

    Rogozea, Liliana; LeaȘu, Florin; Dumitrascu, Dinu Iuliu; Dumitrascu, Dan L

    2015-01-01

    Plague is one of the most impressive diseases in the cultural history of mankind. Its lethality has influenced the evolution of society and it is frequently represented in fine arts and literature. The principality of Transylvania was also affected by this infection, the plague having strongly impacted both economic and social development. Between 1738 and 1739 an important plague epidemic spread in Transylvania. The authors introduce and discuss a less known work on this epidemic, with focus on its impact on the city of Cluj - a book written in 1930 by Dr. Alexandru Lenghel, who later became a target of political persecution during the Stalinist period, while his work entered a cone of shadow.

  15. [Preventive measures against plague and the control of Chinese coolies in colonial Korea].

    Science.gov (United States)

    Kim, Youngsoo

    2014-12-01

    This paper aims to examine the preventive measures taken against the plague in colonial Korea, particularly as applied to the control of Chinese coolies in 1911, soon after the annexation. The Government General of Korea began preventive measures with a train quarantine in Shin'uiju and Incheon in response to the spread of the plague to the Southern Manchuria. Shin' uiju had become urbanized due the development of the transportation network, and the seaport of Incheon was the major hub for traffic with China. Examining the transportation routes for the entry and exit of Chinese to and from Korea makes clear the reason why the Korea Government General initiated preventive measures in mid-January, 1911. The Government General of Korea tried to block the entry of Chinese through the land border crossing with China and through ports of entry, primarily Incheon. During the implementation of the preventive measures, quarantine facilities were built, including a quarantine station and isolation facility in Incheon. It was also needed to investigate the population and residential locations of Chinese in Korea to prevent the spread of plague. A certificate of residence was issued to all Chinese in Korea, which they needed to carry when they travelled. The preventive measures against plague which broke out in Manchuria were removed gradually. However, there was no specific measures against Chinese coolies, those who had migrated from China to work in the spring in Korea. Still the Government General of Korea had doubt about an infection of the respiratory system. As a result, the labor market in colonial Korea underwent changes in this period. The Government General recruited Korean laborers, instead of Chinese coolies whose employment had been planned. This move explains the Government General's strong preventive measures against plague and uncertainty in the route of plague infection, which influenced subsequent regulations on the prohibition of Chinese coolies working on

  16. Age at Vaccination May Influence Response to Sylvatic Plague Vaccine (SPV) in Gunnison's Prairie Dogs (Cynomys gunnisoni).

    Science.gov (United States)

    Rocke, Tonie E; Tripp, Dan; Lorenzsonn, Faye; Falendysz, Elizabeth; Smith, Susan; Williamson, Judy; Abbott, Rachel

    2015-06-01

    Gunnison's prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or "montane" population and a C. g. zuniensis or "prairie" population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P plague challenge at a much higher rate than adults (P plague in the C. g. gunnisoni or "montane" populations of Gunnison's prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

  17. Spatial distribution patterns of plague hosts : point pattern analysis of the burrows of great gerbils in Kazakhstan

    NARCIS (Netherlands)

    Wilschut, Liesbeth I; Laudisoit, Anne; Hughes, Nelika K; Addink, Elisabeth A; de Jong, Steven M; Heesterbeek, Hans A P; Reijniers, Jonas; Eagle, Sally; Dubyanskiy, Vladimir M; Begon, Mike

    AIM: The spatial structure of a population can strongly influence the dynamics of infectious diseases, yet rarely is the underlying structure quantified. A case in point is plague, an infectious zoonotic disease caused by the bacterium Yersinia pestis. Plague dynamics within the Central Asian desert

  18. Spatial analysis and identification of high risk plague regions in Pakistan based on associated rodent species distribution.

    Science.gov (United States)

    Shabbir, Madiha; Aleem, Maha; Javed, Sundus; Wagner, David M; Keim, Paul S; Eqani, Syed Ali Musstjab Akbar Shah; Bokhari, Habib

    2016-08-02

    Plague, caused by Yersinia pestitis, is an infectious bacterial disease that has a high fatality rate if untreated. Rodents are plague reservoirs and play an important role in disease spread. Plague cases have been reported extensively since the second pandemic from the 14th century in countries sharing borders with Pakistan, such as China and India, as well as nearby countries including Russia and central Asia. Despite being centrally located in a plague-infested geographical zone, there has been no plague incidence reported from Pakistan. This study aims to pinpoint some of the potentially important aspects of the disease, which have to be considered when assessing potential risk associated with a plague outbreak in Pakistan. In this context, the occurrence and distribution of plague-associated rodent reservoirs in different regions of Pakistan in relation to those found in the neighboring countries were mapped. In addition, the climatic factors that may also influence disease spread by affecting the growth of the bacteria are also discussed. The combined epidemiological and ecological surveillance studies suggest a prevalence of several potential rodent carriers in certain districts with the possibility of a plague outbreak in Pakistan.

  19. Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

    Science.gov (United States)

    Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E.

    2011-01-01

    Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations 10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

  20. Transverse--Harris--lines in a skeletal population from the 1711 Danish plague site

    DEFF Research Database (Denmark)

    Fiscella, Gabriela N; Bennike, Pia; Lynnerup, Niels

    2008-01-01

    This study examines the occurrence and distribution of transverse lines in skeletal remains from the Copenhagen site, a plague cemetery dated 1711 AD. A relatively low frequency for evidence of line formation was observed in the individuals comprising the total sample and no transverse lines were...... present in the subadult category. This paper addresses the pattern of transverse line occurrence and cohort-specific distribution in a plague sample in light of the multiple factors influencing line formation and resorption and discusses the significance of transverse lines as measures of non...

  1. Socio-epidemiological determinants of 2002 plague outbreak in Himachal Pradesh, India: a qualitative study.

    Science.gov (United States)

    Goel, Sonu; Kaur, Harvinder; Gupta, Anil Kumar; Chauhan, Umesh; Singh, Amarjeet

    2014-04-08

    This qualitative investigation was conducted to determine the socio-epidemiological factors related to the plague outbreak (2002) in Himachal Pradesh (HP), India. The data for socio-epidemiological factors related to the plague outbreak (2002) in HP was obtained from residents through 150 in-depth Interviews (IDI) and 30 Focus Group Discussions (FGD) during six visits (from May 2011 to April 2012) by the research team. Natives, health officials and the nomadic population were interviewed. According to their opinion and viewpoints data was collected and their lifestyle and hunting practices were studied in detail. Tape recorders were used during various FGDs and IDIs. The interviews and FGDs were later transcribed and coded. In-depth analysis of the recorded data was done using an inductive thematic analysis approach. The study reports that the outbreak in 2002 in a few villages of Himachal Pradesh was that of plague and it occurred by the contact of an index case with wild animals after hunting and de-skinning. The first wave of plague transmission which took 16 lives of residents was followed by a second wave of transmission in a ward of a tertiary care hospital where one visitor acquired it from relatives of the index case and succumbed. The life-style practices of residents (hunting behavior, long stay in caves and jungles, overcrowding in houses, poor hygiene and sanitation, belief in 'God' and faith healers for cure of diseases) was optimal for the occurrence and rapid spread of such a communicable disease. The man-rodent contact is intensified due to the practice of hunting in such a rodent-ridden environment. The residents harbor a strong belief that plague occurs due to the wrath of gods. Various un-reported outbreaks of plague were also observed by officials, residents and old folk. The persistence of plague in HP is favoured by its hilly terrain, inaccessible areas, inclement weather (snow) in winters, unhygienic lifestyle, hunting practices of residents

  2. Assessment of Rhodamine B for labelling the plague reservoir Rattus rattus in Madagascar

    OpenAIRE

    Rahelinirina, S.; Duplantier, Jean-Marc; Ratsimba, M.; Ratovonjato, J.; Ramilijaona, O.; Papillon, Yves; Rahalison, L.

    2010-01-01

    The black rat is the main plague reservoir in rural foci in Madagascar, inside the villages as well as in the cultivated areas around. We have evaluated the potentialities of mass-marking of rats, using baits containing Rhodamine B (RB) in order to get a tool to study the movements of rats and to understand the spread of plague. Laboratory experiments demonstrated that: (i) rats were more attracted by the rodent granules and peanut butter; (ii) incorporation of RB in baits did not reduce thei...

  3. Use of rhodamine B as a biomarker for oral plague vaccination of prairie dogs.

    Science.gov (United States)

    Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E

    2011-07-01

    Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of black-tailed prairie dogs (C. ludovicianus) when used at concentrations 10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

  4. The use of high-resolution remote sensing for plague surveillance in Kazakhstan

    DEFF Research Database (Denmark)

    Addink, E A; De Jong, S M; Davis, S A

    2010-01-01

    in Kazakhstan the great gerbil is the major host of plague, a social rodent well-adapted to desert environments. Intensive monitoring and prevention of plague in gerbils started in 1947, reducing the number of human cases and mortalities drastically. However, the monitoring is labour-intensive and hence...... of the classification reached 60 and 86%, respectively, providing proof of concept that automatic mapping of burrow systems using high-resolution satellite images is possible. Such maps, by better defining great gerbil foci, locating new or expanding foci and measuring the density of great gerbil burrow systems could...

  5. Ovid’s Aeginetan plague and the metamorphosis of the Georgics

    OpenAIRE

    Heerink, M.A.J.

    2011-01-01

    The influence of the ancient literary tradition upon the Georgics is as broad as it is profound , but in Virgil’s highly allusive didactic poem, the description of the Noric cattle plague at the end of Georgics 3 holds a unique position. As R.F. THOMAS comments, "nowhere else does Virgil draw so deeply from a single source" . This source is Lucretius’ account of the human plague of Athens in the sixth book of his De Rerum Natura, which in its turn draws heavily on Thucydides’ account of the s...

  6. The Black Death | Matemu | Dar Es Salaam Medical Students' Journal

    African Journals Online (AJOL)

    occurred in Vietnam, India, Algeria, Madagascar, and the northeastern part of the Democratic Republic of the Congo. [2] During 2000-2001, 95% of the world's cases occurred in Africa. Bubonic plague has a 1-15% mortality rate in treated cases and a 40-60% mortality rate in untreated cases. Conclusions Bubonic plague is ...

  7. Contrasted patterns of selection on MHC-linked microsatellites in natural populations of the Malagasy plague reservoir.

    Directory of Open Access Journals (Sweden)

    Charlotte Tollenaere

    Full Text Available Plague (Yersinia pestis infection is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2. For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21 showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague.

  8. Contrasted patterns of selection on MHC-linked microsatellites in natural populations of the Malagasy plague reservoir.

    Science.gov (United States)

    Tollenaere, Charlotte; Ivanova, Svilena; Duplantier, Jean-Marc; Loiseau, Anne; Rahalison, Lila; Rahelinirina, Soanandrasana; Brouat, Carine

    2012-01-01

    Plague (Yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus) is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar) are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2). For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague.

  9. [Risk assessments and control strategies of plague in five key surveillance counties, Zhejiang province].

    Science.gov (United States)

    Shi, Guoxiang; Ju, Cheng; Zhang, Rong; Zhang, Zheng; Sun, Jimin; Wang, Miaoruo; Zhang, Xiaohe; Ye, Xianming; Zhu, Zhihong; Xing, Jianguang; Liao, Xiaowei; Chen, Zhiping

    2015-10-01

    To analyze the epidemiology data on plague in five counties in Zhejiang province and to evaluate the risk of plague in theses areas. We selected five monitoring stations as a risk assessment (Qingyuan county, Longquan city, Yiwu city, Wencheng county, and Ruian city) in Zhejiang province where the plague epidemic more serious in the history. At least one constant site and 1-4 variable sites where plague occurred in history were selected for monitoring. We collected the five counties (cities) surveillance data of indoor rat density, indoor Rattus flavipectus density, the Xenopsylla cheopis index of rat, the Xenopsylla cheopis index of Rattus flavipectus in 1995-2014. Isolation of Yersinia pestis was conducted among 171,201 liver samples and F1 antibody were detected among 228,775 serum samples. Risk matrix, Borda count method, and Delphi approach were conducted to assess risk of the plague of five counties (cities) in Zhejiang province. Indoor rat density in Qingyuan county, Longquan city, Yiwu city, Wencheng county, Ruian city was 1.58%-5.50%, 1.13%-9.76%, 0.56%-3.67%, 2.83%-16.08%, 7.16%-15.96%, respectively; Indoor Rattus flavipectus density of five counties (cities) was 0.08%-2.23%, 0-2.02%, 0-0.54%, 0.71%-5.58%, 0.55%-4.92%, respectively. The Xenopsylla cheopis index of rat in Qingyuan county and Wencheng county was 0.011-0.500 and 0.015-0.227, respectively; The Xenopsylla cheopis index of Rattus flavipectus of Qingyuan county and Wencheng county was 0.119-3.412 and 0.100-1.430, respectively; Ruian City and Yiwu city cannot collected Xenopsylla cheopis, Long quan city only collected the Xenopsylla cheopis index of rat in the five years. Yersinia pestis were not isolated in five counties (cities).There were 3 Apodemus agrarius samples positive of plague F1 antibody test, in Longquan city and Yiwu city in 2005. Borda count method to assess the Longquan city, Yiwu (Borda point were both 321) plague risk was higher than three other regions; Delphi approach to

  10. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

    Directory of Open Access Journals (Sweden)

    Rasha Hammamieh

    Full Text Available Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre-symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential.

  11. [Analysis on the results of etiology and serology of plague in Qinghai province from 2001 to 2010].

    Science.gov (United States)

    Yang, Yonghai; Wang, Mei; Zhao, Xiaolong; Zhao, Zhongzhi; Zhang, Aiping; Wei, Rongjie; Wei, Baiqing; Wang, Zuyun

    2014-02-01

    To analyze the results of etiology and serology of plague among human and infected animals in Qinghai province from 2001 to 2010. Thirty-seven cases of human infected with plague, 53 541 different animal samples, 5 685 sets of vector insects flea and 49 039 different animal serum samples were obtained between 2001 and 2010. A total of 7 811 samples of serum from healthy farmers and herdsmen in 14 counties in Qinghai from 2005 to 2007 were collected. Yersinia pestis (Y. pestis) were detected in visceral and secretions from human, infected animals and vector insects, respectively. Plague antigen was detected by reverse indirect hemagglutination assay (RIHA) in those samples. Indirect hemagglutination assay (IHA) was used to test plague FI antibody in serum of human and infected animals. 37 human plague cases were confirmed, 21 strains of plague Y. pestis were isolated from human cases and 14 positive were detected out. 133 of 7 811 samples of human serum were IHA positive, with the positive rate at 1.7%. A total of 146 strains of plague were isolated from infected animals and vector insects, 99 out of which were from infected animals, with a ratio of Marmota himalayan at 72.7% (72/99) and the other 47 were from vector insects, with a ratio of callopsylla solaris at 68.1% (32/47). The number of IHA and PIHA positive were 300 and 10, respectively. A total of 3 animals and 3 insects species were identified as new epidemic hosts for plague. The natural plague focus of Microtus fuscus was discovered and confirmed and coexisted with natural focus of Marmota himalayan in Chengduo county, Yushu prefecture. The epidemic situation of plague is distributed mainly in Haixi, Yushu and Hainan prefectures. From 2001 to 2010, animal infected with plague was detected in successive years and human plague was very common in Qinghai. New infected animals and vector insects species and new epidemic areas were confirmed, hence the trend of plague prevalence for humans and animals is very

  12. Remote sensing for landscape epidemiology : spatial analysis of plague hosts in Kazakhstan

    NARCIS (Netherlands)

    Wilschut, L.I.

    2015-01-01

    The spatial distribution of hosts is a crucial aspect for the understanding of infectious disease dynamics. In Kazakhstan, the great gerbil (Rhombomys opimus) is the main host for plague (Yersinia pestis infection) and poses a public health threat, yet their spatial distribution is unknown. Great

  13. Evaluation of systemic insecticides mixed in rodenticide baits for plague vector control

    DEFF Research Database (Denmark)

    Larsen, Kim Søholt; Lodal, Jens

    1997-01-01

    Rodenticide baits containing systemic insecticides were evaluated in the laboratory for their palatability to the house rat Rattus rattus and for their toxicity against the oriental rat flea Xenopsylla cheopis - both animals are important Vectors of plague in Africa. The test bait and a non...

  14. Protecting Black-Footed Ferrets and Prairie Dogs Against Sylvatic Plague

    Science.gov (United States)

    Rocke, Tonie E.

    2008-01-01

    Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at other federal agencies and the University of Wisconsin, are developing and testing vaccines that can be used to protect black-footed ferrets and prairie dogs against plague. The black-footed ferret is commonly regarded as the most endangered mammal in North America, and sylvatic plague is a major impediment to its recovery. The three prairie dog species (Gunnison's, black-tailed, and white-tailed prairie dogs), upon which the ferret depends for food and whose burrows they use for shelter, have been drastically reduced from historical levels, resulting in the near extinction of the ferret. All three species are considered 'at risk' and have been petitioned for listing as 'threatened' or 'endangered' by the U.S. Fish and Wildlife Service (FWS). Additionally, the Utah prairie dog is listed as threatened and the Mexican prairie dog is considered endangered in Mexico. Like the black-footed ferret, all five prairie dog species are highly susceptible to plague and regularly experience outbreaks with devastating losses. Controlling plague outbreaks in prairie dogs and ferrets is a vital concern for ongoing recovery programs and conservation efforts for both species.

  15. Demographic and spatio-temporal variation in human plague at a persistent focus in Tanzania

    DEFF Research Database (Denmark)

    Davis, S; Makundi, R H; Machang'u, R S

    2006-01-01

    Human plague in the Western Usambara Mountains in Tanzania has been a public health problem since the first outbreak in 1980. The wildlife reservoir is unknown and eradication measures that have proved effective elsewhere in Tanzania appear to fail in this region. We use census data from 2002 and...

  16. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis.

    Science.gov (United States)

    Achtman, M; Zurth, K; Morelli, G; Torrea, G; Guiyoule, A; Carniel, E

    1999-11-23

    Plague, one of the most devastating diseases of human history, is caused by Yersinia pestis. In this study, we analyzed the population genetic structure of Y. pestis and the two other pathogenic Yersinia species, Y. pseudotuberculosis and Y. enterocolitica. Fragments of five housekeeping genes and a gene involved in the synthesis of lipopolysaccharide were sequenced from 36 strains representing the global diversity of Y. pestis and from 12-13 strains from each of the other species. No sequence diversity was found in any Y. pestis gene, and these alleles were identical or nearly identical to alleles from Y. pseudotuberculosis. Thus, Y. pestis is a clone that evolved from Y. pseudotuberculosis 1,500-20,000 years ago, shortly before the first known pandemics of human plague. Three biovars (Antiqua, Medievalis, and Orientalis) have been distinguished by microbiologists within the Y. pestis clone. These biovars form distinct branches of a phylogenetic tree based on restriction fragment length polymorphisms of the locations of the IS100 insertion element. These data are consistent with previous inferences that Antiqua caused a plague pandemic in the sixth century, Medievalis caused the Black Death and subsequent epidemics during the second pandemic wave, and Orientalis caused the current plague pandemic.

  17. God as father: the representation of the tenth plague in children's ...

    African Journals Online (AJOL)

    The Book of Exodus' account of the ten plagues as moment of Israelite liberation from Egyptian servitude is particularly poignant. The troublesome nature of the story's climax — the slaying of the firstborn — proves difficult to relate to a contemporary child audience in light of the nature and seeming injustice of the ...

  18. Ovid’s Aeginetan plague and the metamorphosis of the Georgics

    NARCIS (Netherlands)

    Heerink, M.A.J.

    2011-01-01

    The influence of the ancient literary tradition upon the Georgics is as broad as it is profound , but in Virgil’s highly allusive didactic poem, the description of the Noric cattle plague at the end of Georgics 3 holds a unique position. As R.F. THOMAS comments, "nowhere else does Virgil draw so

  19. Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague

    Centers for Disease Control (CDC) Podcasts

    2014-11-18

    Sarah Gregory reads an abridged version of the essay, Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague.  Created: 11/18/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/20/2014.

  20. A Scottish doctor's association with the discovery of the plague bacillus.

    Science.gov (United States)

    Yule, W L

    1995-12-01

    Plague killed at least a quarter of the population of Europe in 1348. This was the first wave of the epidemic known as 'The Black Death' which continued for two years and then recurred sporadically till the late 17th Century. In London in 1603, 22.6% of the population died from plague and in the outbreak known as The Great Plague of London in 1694 there were over 70,000 deaths out of a population of 460,000. Many English villages were completely wiped out at this time. Marseilles suffered severely in 1720. The next serious outbreak was in Canton in China in 1894, the disease spreading to Hong Kong. 80,000 died, the great majority of these being in China. A Scottish doctor played an important part in the management of this epidemic when it reached the British colony, and by chance found himself on the periphery of the controversy about who first discovered Yersinia Pestis, the Gram negative bacillus that causes plague.

  1. Survey of the crayfisch plague pathogen presence in the Netherlands reveals a new Aphanomyces astaci carrier.

    NARCIS (Netherlands)

    Tilmans, M.H.J.; Mrugala, A.; Svoboda, J.; Engelsma, M.Y.; Petie, M.; Soes, D.M.; Nutbeam-Tuffs, S.; Oidtmann, B.; Roessink, I.; Petrusek, A.

    2014-01-01

    North American crayfish species as hosts for the crayfish plague pathogen Aphanomyces astaci contribute to the decline of native European crayfish populations. At least six American crayfish species have been reported in the Netherlands but the presence of this pathogenic oomycete with substantial

  2. Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th-Centruy Alghero, Sardinia

    Centers for Disease Control (CDC) Podcasts

    2013-10-28

    Reginald Tucker reads an abridged version of the Emerging Infectious Diseases’ historical Review, Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th -Centruy Alghero, Sardinia.  Created: 10/28/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/30/2013.

  3. Lessons from the History of Quarantine, from Plague to Influenza A

    Centers for Disease Control (CDC) Podcasts

    2013-05-08

    Reginald Tucker reads an abridged version of the Emerging Infectious Diseases’ Historical Review, Lessons from the History of Quarantine, from Plague to Influenza A.  Created: 5/8/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 5/15/2013.

  4. REINTRODUCTION OF NOBLE CRAYFISH ASTACUS ASTACUS AFTER CRAYFISH PLAGUE IN NORWAY

    Directory of Open Access Journals (Sweden)

    TAUGBØL T.

    2004-01-01

    Full Text Available The Glomma and Halden watercourses in Norway were hit by crayfish plague in 1987 and 1989. Reintroduction of the noble crayfish started in 1989 in the Glomma and in 1995 in the Halden watercourse. Norway has especially good conditions for reintroduction of the native crayfish after crayfish plague, as there is no alien plague-carrying crayfish species in the country. In the Glomma watercourse, approx. 15 000 adult crayfish and 10 000 juveniles have been stocked while in the Halden watercourse the figures are 19 000 adults and 26 500 juveniles. All stocking sites were previously regarded as very good crayfish localities. Four years after stocking, natural recruitment was recorded at all adult crayfish stocking sites in the Glomma watercourse and at most sites in the Halden watercourse. Current crayfish density is, however, much lower than pre-plague densities even at the sites where population development has been in progress for more than 10 years. Extensive post-stocking movements were recorded among adult crayfish. Some sites seemed more suitable for settling, resulting in a great variation in CPUE between the different test-fishing sites. Juveniles seem more appropriate as stocking material if the goal is to re-establish a population in a particular area, due to their stationary behaviour, which seems to remain as they grow larger.

  5. The galenic plague: a breakdown of the imperial pathocoenosis. Pathocoenosis and longue durée.

    Science.gov (United States)

    Gourevitch, Danielle

    2005-01-01

    Is 'pathocoenosis', a notion conceived and a word coined by Mirko Grmek (1969), useful as far as ancient history is concerned? The author is interested in Galenic pathocoenosis, that of doctor Galen and his Emperor Marcus Aurelius (IInd cent. A.D.), when a new 'pestilence' or 'plague' (smallpox?) devastated the whole empire, from Mesopotamia to the Danube at least.

  6. Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in Montana

    Science.gov (United States)

    Matchett, Marc R.; Biggins, Dean E.; Carlson, Valerie; Powell, Bradford; Rocke, Tonie E.

    2010-01-01

    Black-footed ferrets (Mustela nigripes) require extensive prairie dog colonies (Cynomys spp.) to provide habitat and prey. Epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. In addition to epizootics, we hypothesized that enzootic plague, that is, presence of disease-causing Yersinia pestis without any noticeable prairie dog die off, may also affect ferret survival. We reduced risk of plague on portions of two ferret reintroduction areas by conducting flea control for 3 years. Beginning in 2004, about half of the ferrets residing on dusted and nondusted colonies were vaccinated against plague with an experimental vaccine (F1-V fusion protein). We evaluated 6-month reencounter rates (percentage of animals observed at the end of an interval that were known alive at the beginning of the interval), an index to survival, for ferrets in four treatment groups involving all combinations of vaccination and flea control. For captive-reared ferrets (115 individuals observed across 156 time intervals), reencounter rates were higher for vaccinates (0.44) than for nonvaccinates (0.23, p = 0.044) on colonies without flea control, but vaccination had no detectable effect on colonies with flea control (vaccinates = 0.41, nonvaccinates = 0.42, p = 0.754). Flea control resulted in higher reencounter rates for nonvaccinates (p = 0.026), but not for vaccinates (p = 0.508). The enhancement of survival due to vaccination or flea control supports the hypothesis that enzootic plague reduces ferret survival, even when there was no noticeable decline in prairie dog abundance. The collective effects of vaccination and flea control compel a conclusion that fleas are required for maintenance, and probably transmission, of plague at enzootic levels. Other studies have demonstrated similar effects of flea control on several species of prairie dogs and, when combined with this study, suggest

  7. Spatiotemporal dynamics of black-tailed prairie dog colonies affected by plague

    Science.gov (United States)

    Augustine, D.J.; Matchett, M.R.; Toombs, T.P.; Cully, J.F.; Johnson, T.L.; Sidle, John G.

    2008-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) are a key component of the disturbance regime in semi-arid grasslands of central North America. Many studies have compared community and ecosystem characteristics on prairie dog colonies to grasslands without prairie dogs, but little is known about landscape-scale patterns of disturbance that prairie dog colony complexes may impose on grasslands over long time periods. We examined spatiotemporal dynamics in two prairie dog colony complexes in southeastern Colorado (Comanche) and northcentral Montana (Phillips County) that have been strongly influenced by plague, and compared them to a complex unaffected by plague in northwestern Nebraska (Oglala). Both plague-affected complexes exhibited substantial spatiotemporal variability in the area occupied during a decade, in contrast to the stability of colonies in the Oglala complex. However, the plague-affected complexes differed in spatial patterns of colony movement. Colonies in the Comanche complex in shortgrass steppe shifted locations over a decade. Only 10% of the area occupied in 1995 was still occupied by prairie dogs in 2006. In 2005 and 2006 respectively, 74 and 83% of the total area of the Comanche complex occurred in locations that were not occupied in 1995, and only 1% of the complex was occupied continuously over a decade. In contrast, prairie dogs in the Phillips County complex in mixed-grass prairie and sagebrush steppe primarily recolonized previously occupied areas after plague-induced colony declines. In Phillips County, 62% of the area occupied in 1993 was also occupied by prairie dogs in 2004, and 12% of the complex was occupied continuously over a decade. Our results indicate that plague accelerates spatiotemporal movement of prairie dog colonies, and have significant implications for landscape-scale effects of prairie dog disturbance on grassland composition and productivity. These findings highlight the need to combine landscape-scale measures of

  8. Exposure of small rodents to plague during epizootics in black-tailed prairie dogs.

    Science.gov (United States)

    Stapp, Paul; Salkeld, Daniel J; Eisen, Rebecca J; Pappert, Ryan; Young, John; Carter, Leon G; Gage, Kenneth L; Tripp, Daniel W; Antolin, Michael F

    2008-07-01

    Plague, caused by the bacterium Yersinia pestis, causes die-offs of colonies of prairie dogs (Cynomys ludovicianus). It has been argued that other small rodents are reservoirs for plague, spreading disease during epizootics and maintaining the pathogen in the absence of prairie dogs; yet there is little empirical support for distinct enzootic and epizootic cycles. Between 2004 and 2006, we collected blood from small rodents captured in colonies in northern Colorado before, during, and for up to 2 yr after prairie dog epizootics. We screened 1,603 blood samples for antibodies to Y. pestis, using passive hemagglutination and inhibition tests, and for a subset of samples we cultured blood for the bacterium itself. Of the four species of rodents that were common in colonies, the northern grasshopper mouse (Onychomys leucogaster) was the only species with consistent evidence of plague infection during epizootics, with 11.1-23.1% of mice seropositive for antibody to Y. pestis during these events. Seropositive grasshopper mice, thirteen-lined ground squirrels (Spermophilus tridecemlineatus), and deer mice (Peromyscus maniculatus) were captured the year following epizootics. The appearance of antibodies to Y. pestis in grasshopper mice coincided with periods of high prairie dog mortality; subsequently, antibody prevalence rates declined, with no seropositive individuals captured 2 yr after epizootics. We did not detect plague in any rodents off of colonies, or on colonies prior to epizootics, and found no evidence of persistent Y. pestis infection in blood cultures. Our results suggest that grasshopper mice could be involved in epizootic spread of Y. pestis, and possibly, serve as a short-term reservoir for plague, but provide no evidence that the grasshopper mouse or any small rodent acts as a long-term, enzootic host for Y. pestis in prairie dog colonies.

  9. Yersinia pestis DNA from skeletal remains from the 6(th century AD reveals insights into Justinianic Plague.

    Directory of Open Access Journals (Sweden)

    Michaela Harbeck

    Full Text Available Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th and 20(th centuries, during which plague was spread around the world, and the second pandemic of the 14(th-17(th centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th-8(th centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics.

  10. Yersinia pestis DNA from skeletal remains from the 6(th) century AD reveals insights into Justinianic Plague.

    Science.gov (United States)

    Harbeck, Michaela; Seifert, Lisa; Hänsch, Stephanie; Wagner, David M; Birdsell, Dawn; Parise, Katy L; Wiechmann, Ingrid; Grupe, Gisela; Thomas, Astrid; Keim, Paul; Zöller, Lothar; Bramanti, Barbara; Riehm, Julia M; Scholz, Holger C

    2013-01-01

    Yersinia pestis, the etiologic agent of the disease plague, has been implicated in three historical pandemics. These include the third pandemic of the 19(th) and 20(th) centuries, during which plague was spread around the world, and the second pandemic of the 14(th)-17(th) centuries, which included the infamous epidemic known as the Black Death. Previous studies have confirmed that Y. pestis caused these two more recent pandemics. However, a highly spirited debate still continues as to whether Y. pestis caused the so-called Justinianic Plague of the 6(th)-8(th) centuries AD. By analyzing ancient DNA in two independent ancient DNA laboratories, we confirmed unambiguously the presence of Y. pestis DNA in human skeletal remains from an Early Medieval cemetery. In addition, we narrowed the phylogenetic position of the responsible strain down to major branch 0 on the Y. pestis phylogeny, specifically between nodes N03 and N05. Our findings confirm that Y. pestis was responsible for the Justinianic Plague, which should end the controversy regarding the etiology of this pandemic. The first genotype of a Y. pestis strain that caused the Late Antique plague provides important information about the history of the plague bacillus and suggests that the first pandemic also originated in Asia, similar to the other two plague pandemics.

  11. Single-Nucleotide Polymorphisms Reveal Spatial Diversity Among Clones of Yersinia pestis During Plague Outbreaks in Colorado and the Western United States.

    Science.gov (United States)

    Lowell, Jennifer L; Antolin, Michael F; Andersen, Gary L; Hu, Ping; Stokowski, Renee P; Gage, Kenneth L

    2015-05-01

    In western North America, plague epizootics caused by Yersinia pestis appear to sweep across landscapes, primarily infecting and killing rodents, especially ground squirrels and prairie dogs. During these epizootics, the risk of Y. pestis transmission to humans is highest. While empirical models that include climatic conditions and densities of rodent hosts and fleas can predict when epizootics are triggered, bacterial transmission patterns across landscapes, and the scale at which Y. pestis is maintained in nature during inter-epizootic periods, are poorly defined. Elucidating the spatial extent of Y. pestis clones during epizootics can determine whether bacteria are propagated across landscapes or arise independently from local inter-epizootic maintenance reservoirs. We used DNA microarray technology to identify single-nucleotide polymorphisms (SNPs) in 34 Y. pestis isolates collected in the western United States from 1980 to 2006, 21 of which were collected during plague epizootics in Colorado. Phylogenetic comparisons were used to elucidate the hypothesized spread of Y. pestis between the mountainous Front Range and the eastern plains of northern Colorado during epizootics. Isolates collected from across the western United States were included for regional comparisons. By identifying SNPs that mark individual clones, our results strongly suggest that Y. pestis is maintained locally and that widespread epizootic activity is caused by multiple clones arising independently at small geographic scales. This is in contrast to propagation of individual clones being transported widely across landscapes. Regionally, our data are consistent with the notion that Y. pestis diversifies at relatively local scales following long-range translocation events. We recommend that surveillance and prediction by public health and wildlife management professionals focus more on models of local or regional weather patterns and ecological factors that may increase risk of widespread

  12. [IMPACT OF CASPIAN SEA LEVEL FLUCTUATIONS ON THE EPIZOOTIC ACTIVITY OF THE CASPIAN SANDY NATURAL PLAGUE FOCUS].

    Science.gov (United States)

    Popov, N V; Udovikov, A I; Eroshenko, G A; Karavaeva, T B; Yakovlev, S A; Porshakov, A M; Zenkevich, E S; Kutyrev, V V

    2016-01-01

    There is evidence that in 1923-2014 the sharp aggravations of the epizootic situation of plague in the area of its Caspian sandy natural focus after long interepizootic periods are in time with the ups of the Caspian Sea in the extrema of 11-year solar cycles. There were cases of multiple manifestations of plague in the same areas in the epizootic cycles of 1946-1954, 1979-1996, 2001, and 2013-2014. The paper considers the possible role of amebae of the genus Acanthamoeba and nematodes, the representatives of the orders Rhabditida and Tylenchida in the microfocal pattern of plague manifestations.

  13. In search of the plague. The Greek peninsula faces the black death, 14th to 19th centuries.

    Science.gov (United States)

    Kostis, K P

    1998-01-01

    Histories of the plague are based on the belief that we can locate epidemics in the related sources and classify them according to present-day medical categories. This article rests upon the assumption that present day medical discourse which is based upon laboratory observation is totally incompatible with history which lacks analogous techniques in constructing its own discourse. It explores the possibilities and the limits of a history of the plague based upon the phenomenology of the disease as recorded in the sources that concern the period of the second pandemic of the plague.

  14. Plague Studies in California: A Review of Long-Term Disease Activity, Flea-Host Relationships and Plague Ecology in the Coniferous Forests of the Southern Cascades and Northern Sierra Nevada Mountains

    National Research Council Canada - National Science Library

    Charles R. Smith; James R. Tucker; Barbara A. Wilson; James R. Clover

    2010-01-01

    ... in the northern Sierra Nevada and the Southern Cascade mountains of northeastern California. We identify rodent hosts and their fleas and document long-term plague activity in each habitat type...

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

    Science.gov (United States)

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

    2016-06-08

    Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Effects of weather and plague-induced die-offs of prairie dogs on the fleas of northern grasshopper mice.

    Science.gov (United States)

    Salkeld, Daniel J; Stapp, Paul

    2009-05-01

    Plague, the disease caused by the bacterium Yersinia pestis, can have devastating impacts on black-tailed prairie dogs (Cynomys ludovicianus Ord). Other mammal hosts living on prairie dog colonies may be important in the transmission and maintenance of plague. We examined the flea populations of northern grasshopper mice (Onychomys leucogaster Wied) before, during, and after plague epizootics in northern Colorado and studied the influence of host and environmental factors on flea abundance patterns. Grasshopper mice were frequently infested with high numbers of fleas, most commonly Pleochaetis exilis Jordan and Thrassis fotus Jordan. Flea loads changed in response to both environmental temperature and rainfall. After plague-induced prairie dog die-offs, flea loads and likelihood of infestation were unchanged for P. exilis, but T. fotus loads declined.

  17. Plague studies in California: a review of long-term disease activity, flea-host relationships and plague ecology in the coniferous forests of the Southern Cascades and northern Sierra Nevada mountains.

    Science.gov (United States)

    Smith, Charles R; Tucker, James R; Wilson, Barbara A; Clover, James R

    2010-06-01

    We review 28 years of long-term surveillance (1970-1997) for plague activity among wild rodents from ten locations within three coniferous forest habitat types in the northern Sierra Nevada and the Southern Cascade mountains of northeastern California. We identify rodent hosts and their fleas and document long-term plague activity in each habitat type. The highest seroprevalence for Yersinia pestis occurred in the chipmunks, Tamias senex and T. quadrimaculatus, and the pine squirrel, Tamiasciurus douglasii. The most commonly infected fleas were Ceratophyllus ciliatus and Eumolpianus eumolpi from chipmunks and Oropsylla montana and O. idahoensis from ground squirrels. Serological surveillance demonstrated that populations of T. senex, T. quadrimaculatus and T. douglasii are moderately resistant to plague, survive infection, and are, therefore, good sentinels for plague activity. Recaptured T. senex and T. quadrimaculatus showed persistence of plague antibodies and evidence of re-infection over a two year period. These rodent species, their fleas, and the ecological factors common to the coniferous forest habitats likely promote the maintenance of plague foci in northeastern California.

  18. Athumia and philanthrôpia. Social reactions to plagues in late antiquity and early Byzantine society.

    Science.gov (United States)

    Leven, K H

    1995-01-01

    Thucydides' description of the plague at Athens stands as a paradigm that influenced eyewitness accounts throughout Greek and Byzantine history. Christian authors in Late Antiquity use his dark picture as heathen background against which they highlight Christian virtues of charity and mercy. The descriptions of the Justinianic plague of AD 542 rely on Thucydides not only stylistically but also in substance, as the early Byzantine society reacts like the people of ancient Athens rather than early Christian communities.

  19. Interannual variability of human plague occurrence in the Western United States explained by tropical and North Pacific Ocean climate variability.

    OpenAIRE

    Ari, Tamara Ben; Gershunov, Alexander; Tristan, Rouyer; Cazelles, Bernard; Gage, Kenneth; Stenseth, Nils C.

    2010-01-01

    International audience; Plague is a vector-borne, highly virulent zoonotic disease caused by the bacterium Yersinia pestis. It persists in nature through transmission between its hosts (wild rodents) and vectors (fleas). During epizootics, the disease expands and spills over to other host species such as humans living in or close to affected areas. Here, we investigate the effect of large-scale climate variability on the dynamics of human plague in the western United States using a 56-year ti...

  20. Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus

    Science.gov (United States)

    Brouat, Carine; Rahelinirina, Soanandrasana; Loiseau, Anne; Rahalison, Lila; Rajerison, Minoariso; Laffly, Dominique; Handschumacher, Pascal; Duplantier, Jean-Marc

    2013-01-01

    Background Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. Methodology/Principal Findings We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150–200 km2 within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. Conclusions/Significance Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations. PMID:23755317

  1. Mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015).

    Science.gov (United States)

    Wang, Xin; Wei, Xiaoyu; Song, Zhizhong; Wang, Mingliu; Xi, Jinxiao; Liang, Junrong; Liang, Yun; Duan, Ran; Tian, Kecheng; Zhao, Yong; Tang, Guangpeng; You, Lv; Yang, Guirong; Liu, Xuebin; Chen, Yuhuang; Zeng, Jun; Wu, Shengrong; Luo, Shoujun; Qin, Gang; Hao, Huijing; Jing, Huaiqi

    2017-03-01

    Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma. We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years' surveillance. The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

  2. Plague circulation and population genetics of the reservoir Rattus rattus: the influence of topographic relief on the distribution of the disease within the Madagascan focus.

    Directory of Open Access Journals (Sweden)

    Carine Brouat

    Full Text Available Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar.We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2 within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats.Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations.

  3. Plague circulation and population genetics of the reservoir Rattus rattus: the influence of topographic relief on the distribution of the disease within the Madagascan focus.

    Science.gov (United States)

    Brouat, Carine; Rahelinirina, Soanandrasana; Loiseau, Anne; Rahalison, Lila; Rajerison, Minoariso; Laffly, Dominique; Handschumacher, Pascal; Duplantier, Jean-Marc

    2013-01-01

    Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations.

  4. Early host cell targets of Yersinia pestis during primary pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Roger D Pechous

    Full Text Available Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

  5. Level of damages and economical threshold, decisive aspects in the integrated management of plagues.

    Directory of Open Access Journals (Sweden)

    Rafael Meneses

    2011-03-01

    Full Text Available The establishment and application of economical levels demand a procedure to find with precision the insects population in a given moment. In the integrated management of plagues is not allowed the idea that any insect which is feeding from a part of plants requires a control action, that is why it is very important to determine the real effect that this insect population causes to the cultivation. Any decrease in the crop, constitutes a real waste of time; but when the economical level is defined, it is included an additional factor which is the measure cost of the plagues control. The determination of damages of levels is very important for economists, farming experts and specialists; while for producers is very significant its implementation with the objective to count with a sustainable and beneficial agriculture.

  6. High throughput, multiplexed pathogen detection authenticates plague waves in medieval Venice, Italy.

    Directory of Open Access Journals (Sweden)

    Thi-Nguyen-Ny Tran

    Full Text Available BACKGROUND: Historical records suggest that multiple burial sites from the 14th-16th centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics. METHODOLOGY/PRINCIPAL FINDINGS: High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9% samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7% samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype. CONCLUSIONS: These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century.

  7. High throughput, multiplexed pathogen detection authenticates plague waves in medieval Venice, Italy.

    Science.gov (United States)

    Tran, Thi-Nguyen-Ny; Signoli, Michel; Fozzati, Luigi; Aboudharam, Gérard; Raoult, Didier; Drancourt, Michel

    2011-03-10

    Historical records suggest that multiple burial sites from the 14th-16th centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics. High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9%) samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7%) samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype. These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century.

  8. The effects of plague on the distribution of property: Ivrea, Northern Italy 1630.

    Science.gov (United States)

    Alfani, Guido

    2010-03-01

    The demographic effects of the epidemics of plague in Early Modern Europe and their economic consequences illuminate the evolution of property structures and of wealth distribution during and after a mortality crisis. An analysis of the high-quality data available for the Italian city of Ivrea at the time of the 1630 plague shows the exceptional resilience of property structures. Like the social structures of the period, property structures were able to recover quickly, informed as they were by the lessons learnt by trial and error by the patrician families of the late Middle Ages, whose patrimonies had been badly damaged by the Black Death. In a period of recurrent catastrophes that struck European populations during the Old Demographic Regime, apparently 'inegalitarian' institutions seem to have had long-term 'egalitarian' effects.

  9. The plague under Marcus Aurelius and the decline and fall of the Roman Empire.

    Science.gov (United States)

    Fears, J Rufus

    2004-03-01

    The Roman Empire of the second century was a superpower that, in relative terms, dominated its world as much as the United States does today. In 166 AD, a plague broke out od pandemic proportions. The pandemic ravaged the entire extent of the Roman Empire, from its eastern frontiers in Iraq to its western frontiers on the Rhine River and Gaul, modern France, and western Germany. The disease is identified most often as smallpox, but it may have been anthrax. The study of bacterial DNA may enable identification of this plague that ravaged the Roman Empire at recurrent intervals for more than 100 years and that had a significant role in the decline and fall of this great superpower.

  10. Integrating land cover and terrain characteristics to explain plague risks in Western Usambara Mountains, Tanzania: a geospatial approach.

    Science.gov (United States)

    Hieronimo, Proches; Meliyo, Joel; Gulinck, Hubert; Kimaro, Didas N; Mulungu, Loth S; Kihupi, Nganga I; Msanya, Balthazar M; Leirs, Herwig; Deckers, Jozef A

    2014-07-01

    Literature suggests that higher resolution remote sensing data integrated in Geographic Information System (GIS) can provide greater possibility to refine the analysis of land cover and terrain characteristics for explanation of abundance and distribution of plague hosts and vectors and hence of health risk hazards to humans. These technologies are not widely used in East Africa for studies on diseases including plague. The objective of this study was to refine the analysis of single and combined land cover and terrain characteristics in order to gain an insight into localized plague infection risks in the West Usambara Mountains in north-eastern Tanzania. The study used a geospatial approach to assess the influence of land cover and terrain factors on the abundance and spatial distribution of plague hosts (small mammals) and plague vectors (fleas). It considered different levels of scale and resolution. Boosted Regression Tree (BRT) statistical method was used to clarify the relationships between land cover and terrain variables with small mammals and fleas. Results indicate that elevation positively influenced the presence of small mammals. The presence of fleas was clearly influenced by land management features such as miraba. Medium to high resolution remotely sensed data integrated in a GIS have been found to be quite useful in this type of analysis. These findings contribute to efforts on plague surveillance and awareness creation among communities on the probable risks associated with various landscape factors during epidemics.

  11. Age at vaccination may influence response to sylvatic plague vaccine (SPV) in Gunnison’s prairie dogs (Cynomys gunnisoni)

    Science.gov (United States)

    Rocke, Tonie E.; Tripp, Daniel W.; Lorenzsonn, Faye; Falendysz, Elizabeth A.; Smith, Susan; Williamson, Judy L.; Abbott, Rachel C.

    2015-01-01

    Gunnison’s prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or “montane” population and a C. g. zuniensis or “prairie” population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

  12. Identification of Risk Factors Associated with Transmission of Plague Disease in Eastern Zambia.

    Science.gov (United States)

    Nyirenda, Stanley S; Hang'ombe, Bernard M; Machang'u, Robert; Mwanza, Jackson; Kilonzo, Bukheti S

    2017-09-01

    Plague is a fatal, primarily rodent-flea-borne zoonotic disease caused by Yersinia pestis. The identification of risk factors of plague was investigated through questionnaire interview and conducting focus group discussion (FGD) in Sinda and Nyimba districts of eastern Zambia. A total of 104 questionnaires were administered to individual respondents and 20 groups consisting of 181 discussants, which comprised FGD team in this study. The study revealed that trapping, transportation, and preparation of rodents for food exposed the community to rodent and their fleas suggesting that plague may have occurred primarily by either flea bites or contact with infected wild rodents. The study also revealed that most people in communities consumed rodents as part of their regular diet; therefore, contact with small wild mammals was a common practice. The mode of transportation of freshly trapped rodents, in particular, carcasses risked human to flea bites. Questionnaire respondents (75%) and FGD discussants (55%) indicated that trappers preferred to carry rodent carcasses in small bags, whereas 55.8% and 20% respectively, reported hunters carrying carcasses in their pockets. Carrying of carcass skewers on trappers' shoulders was reported by 38.4% and 20% of individual respondents and FGD, respectively. All these activities were exposing humans to rodents and their fleas, the natural reservoirs and vectors of plague, respectively. This study also showed that there is a statistically significant (χ2 = 4.6878, P < 0.05), between digging of rodents from their burrows and the presence of fleas on the hunter's bodies or clothes, which exposes humans to potentially flea bites in an enzootic cycle.

  13. Early Modern “Citation Index”? Medical Authorities in Academic Treatises on Plague (1480–1725)

    OpenAIRE

    Karel Černý

    2012-01-01

    The paper deals with the problem of early modern scientific citations. It attempts to establish a measure of scientific popularity in a specific area of the academic medicine in a way which resembles a modern evaluation of scientific activity (citation index). For this purpose an analysis of a series of plague treatises written between 1480 and 1725 in Europe was conducted. Citations for various historical medical authorities (Hippocrates, Galen, etc.) are given in Tables which reflect a long...

  14. Design and construction of an UAV for plague-control purposes

    OpenAIRE

    Garcia Durban, Alberto; Duijneveld Gavin, Coen

    2014-01-01

    An UAV or Unmanned Aerial Vehicle is a multi-purpose platform that is capable of achieving tasks that lie beyond anything that has ever been achieved thanks to the performance, capabilities and inner characteristics that make these vehicles excel in certain aspects. The technical development of this vehicles is just as remarkable as their possible applications. This project is allocated within one of these yet undeveloped applications, which is the plague control, focusing on the mosquito nes...

  15. A rapid field test for sylvatic plague exposure in wild animals

    Science.gov (United States)

    Abbott, Rachel C.; Hudak, Robert; Mondesire, Roy; Baeten, Laurie A.; Russell, Robin E.; Rocke, Tonie E.

    2014-01-01

    Plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. The most common surveillance method for sylvatic plague is detection of antibodies to Yersinia pestis F1 capsular antigen in sentinel animals, such as coyotes (Canis latrans). Current serologic tests for Y. pestis, hemagglutination (HA) test and enzyme-linked immunosorbent assay (ELISA), are expensive and labor intensive. To address this need, we developed a complete lateral flow device for the detection of specific antibodies to Y. pestis F1 and V antigens. Our test detected anti-F1 and anti-V antibodies in serum and Nobuto filter paper samples from coyotes, and in serum samples from prairie dogs (Cynomys ludovicianus), lynx (Lynx canadensis), and black-footed ferrets (Mustela nigripes). Comparison of cassette results for anti-F1 and anti-V antibodies with results of ELISA or HA tests showed correlations ranging from 0.68 to 0.98. This device provides an affordable, user-friendly tool that may be useful in plague surveillance programs and as a research tool.

  16. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria.

    Science.gov (United States)

    Liu, He; Jiao, Mingli; Zhao, Siqi; Xing, Kai; Li, Ye; Ning, Ning; Liang, Libo; Wu, Qunhong; Hao, Yanhua

    2015-04-01

    The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    Science.gov (United States)

    Eddy, Justin L; Schroeder, Jay A; Zimbler, Daniel L; Bellows, Lauren E; Lathem, Wyndham W

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Immunization of black-tailed prairie dog against plague through consumption of vaccine-laden baits

    Science.gov (United States)

    Rocke, T.E.; Smith, S.R.; Stinchcomb, D.T.; Osorio, J.E.

    2008-01-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis and, along with other wild rodents, are significant reservoirs of plague for other wildlife and humans in the western United States. A recombinant raccoon poxvirus, expressing the F1 antigen of Y. pestis, was incorporated into a palatable bait and offered to three groups (n = 18, 19, and 20) of black-tailed prairie dogs (Cynomys ludovicianus) for voluntary consumption, either one, two, or three times, at roughly 3-wk intervals. A control group (n = 19) received baits containing raccoon poxvirus without the inserted antigen. Mean antibody titers to Y. pestis F1 antigen increased significantly in all groups ingesting the vaccine-laden baits, whereas the control group remained negative. Upon challenge with virulent Y. pestis, immunized groups had higher survival rates (38%) than the unimmunized control group (11%). The mean survival time of groups ingesting vaccine-laden baits either two or three times was significantly higher than that of animals ingesting vaccine-laden baits just one time and of animals in the control group. These results show that oral immunization of prairie dogs against plague provides some protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous (3-10) flea bites. ?? Wildlife Disease Association 2008.

  19. Unreliability and the Animal Narrator in Richard Adams’s The Plague Dogs

    Directory of Open Access Journals (Sweden)

    Anja Höing

    2017-03-01

    Full Text Available Richard Adams’s talking animal story The Plague Dogs (1978, with its deeply genre-atypical mode of narration, offers a multiplicity of avenues to explore the literary animal as animal. The story draws much of its power from the psychological complexity and related unreliability of both canine narrators, two research lab escapees gone feral. Both the terrier Snitter and the black mongrel Rowf are mentally ill and experience a highly subjective, part-fantastic world. In episodes of zero focalization, a sarcastic voice comments on the plot from the off, aggressively attacking a thoroughly anthropocentric superstructure the protagonists themselves are oblivious of, and presenting all that is normally constructed as “rational” in the implied reader’s world as a carnivalesque farce. Combining these equally unreliable narratives, The Plague Dogs creates a unique mixture of what Phelan (2007 calls “estranging” and “bonding” unreliability and brings to light the devastating consequences of anthropocentrism. The Plague Dogs not only defamiliarizes a genre usually committed to conventional means of storytelling, but the dominant Western conception of the status of animals in the world, showing that once we start to read the animal as animal, this sets into motion an avalanche of other concepts in need of re-reading, among them the very ones making up the fundamental pillars of Western societies’ anthropocentric self-conception.

  20. [Recrudescence and geographic extension of the plague in Madagascar from 1980 to 1999].

    Science.gov (United States)

    Ratsitorahina, M; Migliani, R; Ratsifasoamanana, L; Ratsimba, M; Chan Ho Thin, F; Rahalison, L; Chanteau, S

    2001-01-01

    Plague was introduced to Madagascar in 1898, and it has been characterized by a predominant distribution to the central highlands in the following decades. An increase of plague cases has been observed in the past 20 years, in particular in the capital, Antananarivo, and in the coastal town, Mahajanga, after long periods of silence in 28 and 63 years, respectively. A total of 2,982 confirmed or presumptive cases were reviewed in order to describe the changes in the epidemiological pattern of the disease from 1980 through 1999. The mean annual number of plague cases has increased from 33 during the 1980-1984 period to 298 during the 1995-1999 period. A similar trend of distribution has been observed from the first period to the second by an increase of endemic districts above 800 m altitude from 17 to 37. However, the lethality rate has in the same 20 years observation period decreased from 41.6% to 20.7%, probably due to re-enforcing measures as part of the national control program.

  1. First evidence of crayfish plague agent in populations of the marbled crayfish (Procambarus fallax forma virginalis

    Directory of Open Access Journals (Sweden)

    Keller N.S.

    2014-01-01

    Full Text Available The introduction of non-indigenous species and associated diseases can cause declines in indigenous flora and fauna and threaten local biodiversity. The crayfish plague pathogen (Aphanomyces astaci, carried and transmitted by latent infected North American crayfish, can lead to high mortalities in indigenous European crayfish populations. Although the parthenogenetic marbled crayfish (Procambarus fallax (Hagen, 1870  forma virginalis is common in the aquarium trade and has established wild populations in Europe, its carrier status is still unknown. This study investigated one captive and three established wild-living marbled crayfish populations for an infection with the crayfish plague pathogen applying real-time PCR. We demonstrate that captive, as well as two wild marbled crayfish populations were infected by A. astaci. Although infection status in laboratory kept specimens reached high levels, marbled crayfish showed no obviously plague-related mortality. Furthermore, sequence analysis revealed that captive crayfish carried the A. astaci genotype Pc, which has earlier been isolated from the North American red swamp crayfish (Procambarus clarkii. The results indicate that due to its positive carrier status marbled crayfish poses a greater threat to local biodiversity in Europe than considered until now.

  2. Factors influencing uptake of sylvatic plague vaccine baits by prairie dogs

    Science.gov (United States)

    Abbott, Rachel C.; Russell, Robin E.; Richgels, Katherine; Tripp, Daniel W.; Matchett, Marc R.; Biggins, Dean E.; Rocke, Tonie E.

    2017-01-01

    Sylvatic plague vaccine (SPV) is a virally vectored bait-delivered vaccine expressing Yersinia pestis antigens that can protect prairie dogs (Cynomys spp.) from plague and has potential utility as a management tool. In a large-scale 3-year field trial, SPV-laden baits containing the biomarker rhodamine B (used to determine bait consumption) were distributed annually at a rate of approximately 100–125 baits/hectare along transects at 58 plots encompassing the geographic ranges of four species of prairie dogs. We assessed site- and individual-level factors related to bait uptake in prairie dogs to determine which were associated with bait uptake rates. Overall bait uptake for 7820 prairie dogs sampled was 70% (95% C.I. 69.9–72.0). Factors influencing bait uptake rates by prairie dogs varied by species, however, in general, heavier animals had greater bait uptake rates. Vegetation quality and day of baiting influenced this relationship for black-tailed, Gunnison’s, and Utah prairie dogs. For these species, baiting later in the season, when normalized difference vegetation indices (a measure of green vegetation density) are lower, improves bait uptake by smaller animals. Consideration of these factors can aid in the development of species-specific SPV baiting strategies that maximize bait uptake and subsequent immunization of prairie dogs against plague.

  3. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria

    Directory of Open Access Journals (Sweden)

    He Liu

    2015-04-01

    Full Text Available The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa.

  4. The crisis of the sixth century: climatic change, natural disasters and the plague

    Science.gov (United States)

    Hirschfeld, Yizhar

    The Byzantine period (fourth-sixth centuries) is considered an era of peak prosperity in agriculture and trade in the eastern and southern Mediterranean. Paleoclimatic studies have pointed to a significant increase in rainfall from the early fourth century onward, the beginning of a more humid period that lasted some two hundred years. However, the economic prosperity of the Byzantine Empire and its achievements in the fields of urban development and trade were halted in the mid-sixth century. In the second half of the sixth century and through the seventh century we can discern a sharp decline in both urban and rural settlement. The plague known as the "Justinianic plague" broke out in the summer of 541 and spread rapidly via trade ships throughout the Empire. At the same time the period of humid climate that had begun in the fourth century came to an end. For the Byzantine farmer the combination of plague and drought was disastrous. This paper focuses on the circumstances and implications of the severe crisis that affected the Levant during the sixth century.

  5. A rapid field test for sylvatic plague exposure in wild animals.

    Science.gov (United States)

    Abbott, Rachel C; Hudak, Robert; Mondesire, Roy; Baeten, Laurie A; Russell, Robin E; Rocke, Tonie E

    2014-04-01

    Plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. The most common surveillance method for sylvatic plague is detection of antibodies to Yersinia pestis F1 capsular antigen in sentinel animals, such as coyotes (Canis latrans). Current serologic tests for Y. pestis, hemagglutination (HA) test and enzyme-linked immunosorbent assay (ELISA), are expensive and labor intensive. To address this need, we developed a complete lateral flow device for the detection of specific antibodies to Y. pestis F1 and V antigens. Our test detected anti-F1 and anti-V antibodies in serum and Nobuto filter paper samples from coyotes, and in serum samples from prairie dogs (Cynomys ludovicianus), lynx (Lynx canadensis), and black-footed ferrets (Mustela nigripes). Comparison of cassette results for anti-F1 and anti-V antibodies with results of ELISA or HA tests showed correlations ranging from 0.68 to 0.98. This device provides an affordable, user-friendly tool that may be useful in plague surveillance programs and as a research tool.

  6. Immunization of black-tailed prairie dog against plague through consumption of vaccine-laden baits.

    Science.gov (United States)

    Rocke, Tonie E; Smith, Susan R; Stinchcomb, Dan T; Osorio, Jorge E

    2008-10-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis and, along with other wild rodents, are significant reservoirs of plague for other wildlife and humans in the western United States. A recombinant raccoon poxvirus, expressing the F1 antigen of Y. pestis, was incorporated into a palatable bait and offered to three groups (n = 18, 19, and 20) of black-tailed prairie dogs (Cynomys ludovicianus) for voluntary consumption, either one, two, or three times, at roughly 3-wk intervals. A control group (n = 19) received baits containing raccoon poxvirus without the inserted antigen. Mean antibody titers to Y. pestis F1 antigen increased significantly in all groups ingesting the vaccine-laden baits, whereas the control group remained negative. Upon challenge with virulent Y. pestis, immunized groups had higher survival rates (38%) than the unimmunized control group (11%). The mean survival time of groups ingesting vaccine-laden baits either two or three times was significantly higher than that of animals ingesting vaccine-laden baits just one time and of animals in the control group. These results show that oral immunization of prairie dogs against plague provides some protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous (3-10) flea bites.

  7. Reorganizing Hospital Space: The 1894 Plague Epidemic in Hong Kong and the Germ Theory*

    Directory of Open Access Journals (Sweden)

    Kyu-hwan Sihn

    2017-04-01

    Full Text Available This paper examined whether the preventive measures taken by the Hong Kong’s colonial authorities were legitimate during the 1894 Hong Kong plague epidemic, and illuminated the correlation between the plague epidemic and hospital space in Hong Kong in the late 19th century. The quarantine measures taken by the colonial authorities were neither a clear-cut victory for Western medicine nor for a rational quarantine based on scientific medical knowledge. Hong Kong’s medical officials based on the miasma theory, and focused only on house-to-house inspections and forced quarantine or isolation, without encouraging people to wear masks and without conducting disinfection. Even after Hong Kong plague spread, the Hong Kong’s colonial authorities were not interested in what plague bacilli were, but in where they were to be found and how to prevent and control an outbreak of the disease. The germ theory brought significant changes to the disease classification system. Until the 1890s, Hong Kong’s colonial authority had classified cause of death mainly on the basis of symptoms, infectious diseases, parts of the body and diseases of systems. Microbiological analysis of the cause of death in Hong Kong was started by Hunter, a bacteriologist, in 1902. He used bacteriological tests with a microscope to analyze the cause of death. New disease recognition and medical recognition brought large changes to hospital space as well. In particular, from the 1880s to the early 1900s, Western medical circles witnessed shifts from miasma theory to the germ theory, thereby influencing Hong Kong’s hospital spaces. As the germ theory took ground in Hong Kong in 1894, the bacteriological laborato