WorldWideScience

Sample records for bubonic plague model

  1. 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

  2. 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

  3. 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

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

    Science.gov (United States)

    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 R 0 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).

  5. 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.

    2007-01-01

    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

  6. 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.

  7. 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

    2014-01-01

    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 adaption 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. PMID:24675805

  8. 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.

  9. 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

  10. Human bubonic plague transmitted by a domestic cat scratch.

    Science.gov (United States)

    Weniger, B G; Warren, A J; Forseth, V; Shipps, G W; Creelman, T; Gorton, J; Barnes, A M

    1984-02-17

    Bubonic plague was transmitted to a 10-year-old girl in Oregon by a scratch wound inflicted by a domestic cat. The cat probably was infected by contact with infected wild rodents or their fleas. Yersinia pestis was identified in Diamanus montanus fleas collected from an abandoned burrow near the patient's home. Domestic cats may infect humans with Y pestis by inoculation from a scratch.

  11. 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.

  12. 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. PMID:23675291

  13. 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.

  14. 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

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

    Science.gov (United States)

    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

  16. Epidemics which never came: yellow fever (1883) and bubonic plague (1902-1903) in Baja California

    Science.gov (United States)

    Fierros-Hernández, Arturo; Ayala-Zúñiga, Alejandro

    2018-01-01

    This paper seeks to clarify the epidemic panorama that was generated in Baja California in the late nineteenth and early twentieth 20 th century’s, specifically that occurred in 1883 and 1902, years in which it is claimed occurred epidemics of yellow fever and bubonic plague respectively. However, as demonstrated in our study they never occurred due to social-demographic conditions in the area. Copyright: © 2018 SecretarÍa de Salud.

  17. Fumigating the Hygienic Model City: Bubonic Plague and the Sulfurozador in Early-Twentieth-Century Buenos Aires.

    Science.gov (United States)

    Engelmann, Lukas

    2018-07-01

    The 1899/1900 arrival of bubonic plague in Argentina had thrown the model status of Buenos Aires as a hygienic city into crisis. Where the idea of foreign threats and imported epidemics had dominated the thinking of Argentina's sanitarians at that time, plague renewed concerns about hidden threats within the fabric of the capital's dense environment; concerns that led to new sanitary measures and unprecedented rat-campaigns supported by the large-scale application of sulphur dioxide. The article tells the story of early twentieth-century urban sanitation in Buenos Aires through the lens of a new industrial disinfection apparatus. The Aparato Marot, also known as Sulfurozador was acquired and integrated in the capital's sanitary administration by the epidemiologist José Penna in 1906 to materialise two key lessons learned from plague. First, the machine was supposed to translate the successful disinfection practices of global maritime sanitation into urban epidemic control in Argentina. Second, the machine's design enabled public health authorities to reinvigorate a traditional hygienic concern for the entirety of the city's terrain. While the Sulfurozador offered effective destruction of rats, it promised also a comprehensive - and utopian - disinfection of the whole city, freeing it from all imaginable pathogens, insects as well as rodents. In 1910, the successful introduction of the Sulfurozador encouraged Argentina's medico-political elite to introduce a new principle of 'general prophylaxis'. This article places the apparatus as a technological modernisation of traditional sanitary practices in the bacteriological age, which preserved the urban environment - 'el terreno' - as a principal site of intervention. Thus, the Sulfurozador allowed the 'higienistas' to sustain a long-standing utopian vision of all-encompassing social, bodily and political hygiene into the twentieth century.

  18. 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

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Plague dynamics are driven by climate variation

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...

  7. 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

  8. [The plague: An overview and hot topics].

    Science.gov (United States)

    Galy, A; Loubet, P; Peiffer-Smadja, N; Yazdanpanah, Y

    2018-04-05

    Plague is a bacterial zoonosis caused by Yersinia pestis, usually found in fleas and small rodents that constitute the reservoir of the disease. It is transmitted to humans by flea bite, contact with rodents or inhalation of infected droplets. There are three clinical forms: bubonic plague, pulmonary plague and septicemic plague. The usual presentation is a flu-like syndrome possibly accompanied by an inflammatory lymphadenopathy which appears after 1 to 7days of incubation. Bubonic plague has a case fatality rate of about 50% while other forms of plague are almost always fatal without treatment. Diagnosis can be confirmed by usual bacteriological techniques (Gram examination, culture) but also by serological examination, use of rapid diagnostic tests or PCR. Although aminoglycosides are traditionally regarded as the most effective treatment, fluoroquinolones or cyclins are currently recommended in France. Plague is one of the re-emerging diseases according to the WHO and Madagascar suffered in 2017 the most important plague epidemic of the 21st century with more than 2000 cases and 200 deaths. Peru and the Democratic Republic of Congo are also considered endemic areas. Public health measures and a relentless fight against poverty are the cornerstone of the control of the disease. Vaccine improvement in endemic areas may also play an important role. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. 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 Cys 273 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 Cys 273 Ala in lcrV Moreover, the lcrV C273A 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 Cys 273 Ala substitution. Furthermore, macrophages infected by the lcrV C273A 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 Δ gshB 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. IMPORTANCE Yersinia 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

  10. Plague and the gallium scan: case report

    International Nuclear Information System (INIS)

    Stahly, T.L.; Shoop, J.D.

    1975-01-01

    Inflammation in the right axillary lymph nodes and the meninges was detected by 67 Ga-citrate scans in an 11-year-old boy with Yersinia pestis infection. This case provides another example of 67 Ga localizing to areas of infection, indicating potential utility in future cases of bubonic plague

  11. An overview of plague in the United States and a report of investigations of two human cases in Kern county, California, 1995.

    Science.gov (United States)

    Madon, M B; Hitchcock, J C; Davis, R M; Myers, C M; Smith, C R; Fritz, C L; Emery, K W; O'Rullian, W

    1997-06-01

    Plague was confirmed in the United States from nine western states during 1995. Evidence of Yersinia pestis infection was identified in 28 species of wild or domestic mammals. Thirteen of the plague positive species were wild rodents; 15 were predators/carnivores. Yersinia pestis was isolated from eight species of fleas. Seven confirmed cases of human plague were reported in 1995 (New Mexico 3; California 2; Arizona and Oregon 1 each). Five of the seven cases were bubonic; one was septicemic and one a fatal pneumonic case. Months of onset ranged from March through August. In California, during 1995, plague was recorded from 15 of the 58 counties. Over 1,500 animals were tested, of which 208 were plague positive. These included 144 rodents and 64 predators/carnivores. Two confirmed human cases (one bubonic and one fatal pneumonic) occurred, both in Kern County. Case No. 1 was reported from the town of Tehachapi. The patient, a 23 year-old male resident, died following a diagnosis of plague pneumonia. The patient's source of plague infection could not be determined precisely. Field investigations revealed an extensive plague epizootic surrounding Tehachapi, an area of approximately 500-600 square miles (800-970 square kilometers). Case No. 2 was a 57 year-old female diagnosed with bubonic plague; she was placed on an antibiotic regimen and subsequently recovered. The patient lives approximately 20 miles (32 km) north of Tehachapi. Field investigations revealed evidence of a plague epizootic in the vicinity of the victim's residence and adjacent areas. Overall results of the joint field investigations throughout the entire Kern county area revealed a high rate of plague positive animals. Of the numerous samples submitted, 48 non-human samples were plague positive.

  12. 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.

  13. [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.

  14. [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

  15. 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. PMID:22496846

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. [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.

  1. 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

  2. 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.

  3. [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.

  4. 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

  5. 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.

  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. 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

  8. 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.

  9. 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

  10. Collateral Damage and Communicable Disease with Particular Reference to Tactical Nuclear War in Europe.

    Science.gov (United States)

    1978-10-31

    incidence of communicable disease attrib- utable to the radiation exposure. Measles, chicken pox , etc., did occur but were within the normal range. 4.4...SMALLPOX MEXICO MILLIONS 50 1603 BUBONIC PLAGUE LONDON 34,000 14 1628 TYPHUS LYONS, FRANCE 60,000 1665 BUBONIC PLAGUE LONDON 100,000 27 1711 BUBONIC PLAGUE

  11. 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.

    2012-01-01

    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. PMID:22851745

  12. 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

    2011-11-01

    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.

  13. 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.

  14. The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis.

    Science.gov (United States)

    Perry, Robert D; Bobrov, Alexander G; Fetherston, Jacqueline D

    2015-06-01

    Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent.

  15. 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.

  16. 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...... examine six hypotheses that could explain the resulting false positive predictions, namely (i) including end-of-outbreak data erroneously lowers the estimated threshold, (ii) too few gerbils were tested, (iii) plague becomes locally extinct, (iv) the abundance of fleas was too low, (v) the climate...

  17. 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).

  18. 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.

  19. The Black Death

    African Journals Online (AJOL)

    northern and southern Europe that the pathogen responsible is the Yersinia pestis bacterium that causes bubonic ... To describe the risks of getting the disease (Bubonic plague). 2. .... The plague bacillus grows readily on most culture media.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. 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.

  8. 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

  9. Land use determinants of small mammal abundance and distribution in a plague endemic area of Lushoto District, Tanzania.

    Science.gov (United States)

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

    2014-07-01

    Small mammals are considered to be involved in the transmission cycle of bubonic plague, still occurring in different parts of the world, including the Lushoto District in Tanzania. The objective of this study was to determine the relationship between land use types and practices and small mammal abundance and distribution. A field survey was used to collect data in three landscapes differing in plague incidences. Data collection was done both in the wet season (April-June 2012) and dry season (August-October 2012). Analysis of variance and Boosted Regression Trees (BRT) modelling technique were used to establish the relationship between land use and small mammal abundance and distribution. Significant variations (p ≤ 0.05) of small mammal abundance among land use types were identified. Plantation forest with farming, natural forest and fallow had higher populations of small mammals than the other aggregated land use types. The influence of individual land use types on small mammal abundance level showed that, in both dry and wet seasons, miraba and fallow tended to favour small mammals' habitation whereas land tillage practices had the opposite effect. In addition, during the wet season crop types such as potato and maize appeared to positively influence the distribution and abundance of small mammals which was attributed to both shelter and food availability. Based on the findings from this study it is recommended that future efforts to predict and map spatial and temporal human plague infection risk at fine scale should consider the role played by land use and associated human activities on small mammal abundance and distribution.

  10. Low dimensional chaotic models for the plague epidemic in Bombay (1896–1911)

    International Nuclear Information System (INIS)

    Mangiarotti, Sylvain

    2015-01-01

    A plague epidemic broke out in Bombay in 1896 and became endemic. From 1905 to 1911, the epidemic was closely monitored by an Advisory Committee appointed to investigate the causes of the disease in any way. An impressive quantity of information was gathered, analyzed and published. Published data include records of the number of people who died from plague, and of the two main populations of rodents which were infected by plague in Bombay city. In the present paper, these data are revisited using a global modeling technique. This technique is applied to both single and multivariate observational time series. Several models are obtained for which a chaotic behavior can be observed. Obtaining such models proves that the dynamics of plague can be approximated by low-dimensional deterministic systems that can produce chaos. The multivariate models give a strong argument for interactive couplings between the epidemic and the epizootics of the two main species of rat. An interpretation of this coupling is given.

  11. 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.

  12. Distinct CCR2(+) Gr1(+) cells control growth of the Yersinia pestis ΔyopM mutant in liver and spleen during systemic plague.

    Science.gov (United States)

    Ye, Zhan; Uittenbogaard, Annette M; Cohen, Donald A; Kaplan, Alan M; Ambati, Jayakrishna; Straley, Susan C

    2011-02-01

    We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of ΔyopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, ΔyopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and ΔyopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

  13. 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.

  14. 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; Sha, Jian; Erova, Tatiana E; Kozlova, Elena V; Kirtley, Michelle L; Tiner, Bethany L; Andersson, Jourdan A; Chopra, Ashok K

    2015-05-01

    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

  15. 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.

  16. 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 ...

  17. Plague

    Science.gov (United States)

    Abbott, Rachel C.; Rocke, Tonie E.

    2012-01-01

    Plague offers readers an overview of this highly complex disease caused by the bacteria Yersinia pestis. The history of the disease, as well as information about Yersinia pestis and its transmission by fleas, is described. The section Geographic Distribution presents areas of the world and United States where plague occurs most commonly in rodents and humans. Species Susceptibility describes infection and disease rates in rodents, humans, and other animals. Disease Ecology considers the complex relationship among rodents, domestic and wild animals, and humans and explores possible routes of transmission and maintenance of the organism in the environment. The effects of climate change, the potential for Y. pestis to be used as a bioweapon, and the impact of plague on conservation of wildlife are considered in Points to Ponder. Disease Prevention and Control outlines methods of prevention and treatment including vaccination for prairie dogs and black-footed ferrets. A glossary of technical terms is included. Tonie E. Rocke, the senior author and an epizootiologist at the USGS National Wildlife Health Center (NWHC), is a prominent researcher on oral vaccination of prairie dogs to prevent plague. She is currently working to transfer her success in the laboratory to the field to control plague in prairie dogs. Rachel C. Abbott, a biologist at the NWHC, is assisting Dr. Rocke in this process and will coordinate field trials of the vaccine. Milt Friend, first director of the NWHC, wrote the foreword. Plague is intended for scholars and the general public. The material is presented in a simple, straightforward manner that serves both audiences. Numerous illustrations and tables provide easily understood summaries of key points and information.

  18. 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

    Background Plague is a rapidly progressing, serious illness in humans that is likely to be fatal if not treated. It remains a public health threat, especially in sub-Saharan Africa. In spite of plague's highly focal nature, a thorough ecological understanding of the general distribution pattern...... of plague across sub-Saharan Africa has not been established to date. In this study, we used human plague data from sub-Saharan Africa for 1970-2007 in an ecological niche modeling framework to explore the potential geographic distribution of plague and its ecological requirements across Africa. Results We...... 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...

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

    Directory of Open Access Journals (Sweden)

    Kausrud Kyrre

    2010-08-01

    Full Text Available Abstract 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

  20. Xenopsylla cheopis (Siphonaptera: Pulicidae susceptibility to Deltamethrin in Madagascar.

    Directory of Open Access Journals (Sweden)

    Sebastien Boyer

    Full Text Available The incidence of bubonic plague in Madagascar is high. This study reports the susceptibility of 32 different populations of a vector, the flea Xenopsylla cheopis (Siphonaptera: Pulicidae, to the insecticide Deltamethrin. Despite the use of Deltamethrin against fleas, plague epidemics have re-emerged in Madagascar. The majority of the study sites were located in the Malagasy highlands where most plague cases have occurred over the last 10 years. X. cheopis fleas were tested for susceptibility to Deltamethrin (0.05%: only two populations were susceptible to Deltamethrin, four populations were tolerant and 26 populations were resistant. KD50 (50% Knock-Down and KD90 (90% Knock-Down times were determined, and differed substantially from 9.4 to 592.4 minutes for KD50 and 10.4 min to 854.3 minutes for KD90. Susceptibility was correlated with latitude, but not with longitude, history of insecticide use nor date of sampling. Combined with the number of bubonic plague cases, our results suggest that an immediate switch to an insecticide other than Deltamethrin is required for plague vector control in Madagascar.

  1. 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 ...

  2. 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.

  3. 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.

  4. 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 ... them at higher risk. Reported Cases of Human Plague - United States, 1970-2016 Since the mid–20th ...

  5. Genome-scale reconstruction of the metabolic network in Yersinia pestis, strain 91001

    Energy Technology Data Exchange (ETDEWEB)

    Navid, A; Almaas, E

    2009-01-13

    The gram-negative bacterium Yersinia pestis, the aetiological agent of bubonic plague, is one the deadliest pathogens known to man. Despite its historical reputation, plague is a modern disease which annually afflicts thousands of people. Public safety considerations greatly limit clinical experimentation on this organism and thus development of theoretical tools to analyze the capabilities of this pathogen is of utmost importance. Here, we report the first genome-scale metabolic model of Yersinia pestis biovar Mediaevalis based both on its recently annotated genome, and physiological and biochemical data from literature. Our model demonstrates excellent agreement with Y. pestis known metabolic needs and capabilities. Since Y. pestis is a meiotrophic organism, we have developed CryptFind, a systematic approach to identify all candidate cryptic genes responsible for known and theoretical meiotrophic phenomena. In addition to uncovering every known cryptic gene for Y. pestis, our analysis of the rhamnose fermentation pathway suggests that betB is the responsible cryptic gene. Despite all of our medical advances, we still do not have a vaccine for bubonic plague. Recent discoveries of antibiotic resistant strains of Yersinia pestis coupled with the threat of plague being used as a bioterrorism weapon compel us to develop new tools for studying the physiology of this deadly pathogen. Using our theoretical model, we can study the cell's phenotypic behavior under different circumstances and identify metabolic weaknesses which may be harnessed for the development of therapeutics. Additionally, the automatic identification of cryptic genes expands the usage of genomic data for pharmaceutical purposes.

  6. Flea diversity as an element for persistence of plague bacteria in an East African plague focus.

    Directory of Open Access Journals (Sweden)

    Rebecca J Eisen

    Full Text Available Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (~725-1160 m to higher elevation sites within the focus (~1380-1630 m. Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence.

  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. 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...

  9. Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice.

    Science.gov (United States)

    Demeure, Christian E; Blanchet, Charlène; Fitting, Catherine; Fayolle, Corinne; Khun, Huot; Szatanik, Marek; Milon, Geneviève; Panthier, Jean-Jacques; Jaubert, Jean; Montagutelli, Xavier; Huerre, Michel; Cavaillon, Jean-Marc; Carniel, Elisabeth

    2012-01-01

    Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1α, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.

  10. 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

  11. 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.

  12. Human plague occurrences in Africa

    DEFF Research Database (Denmark)

    Neerinckx, Simon; Bertherat, Eric; Leirs, Herwig

    2010-01-01

    Plague remains a public health concern worldwide, but particularly in Africa. Despite the long-standing history of human plague, it is difficult to get a historical and recent overview of the general situation. We searched and screened available information sources on human plague occurrences in ...

  13. 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

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

    Science.gov (United States)

    Lewnard, Joseph A; Townsend, Jeffrey P

    2016-12-20

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

  15. 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 ...

  16. Influences of introduced plague on North American mammals: Implications from ecology of plague in Asia

    Science.gov (United States)

    Biggins, D.E.; Kosoy, M.Y.

    2001-01-01

    Intercontinental movements of invasive species continue to modify the world's ecosystems. The plague bacterium (Yersinia pestis) has colonized and altered animal communities worldwide but has received much more attention as a human pathogen. We reviewed studies on the ecology of Y. pestis in ancient foci of central Asia and in western North America, where the bacterium apparently has become established much more recently. Although rodent populations on both continents are affected dramatically by epizootics of plague, the epidemiologically important species of Asia demonstrate resistance in portions of their populations, whereas those of North America are highly susceptible. Individual variation in resistance, which is widespread in Asian rodents and allows a microevolutionary response, has been documented in few North American species of rodents. Plague increases costs of sociality and coloniality in susceptible hosts, increases benefits of disease resistance in general, and increases benefits of adaptability to variable environments for species at higher trophic levels. Prairie dogs (Cynomys) epitomize taxa with high risk to plague because prairie dogs have uniformly low resistance to plague and are highly social. Relationships to plague are poorly understood for many North American rodents, but more than one-half of the species of conservation concern occur within the geographic range of plague.

  17. Towards a theoretically informed policy against a rakghoul plague outbreak.

    Science.gov (United States)

    Kontopoulos, Dimitrios-Georgios; Kontopoulou, Theano; Ho, Hsi-Cheng; García-Carreras, Bernardo

    2017-12-11

    A long time ago in a galaxy far, far away, the Sith Lord Karness Muur engineered the rakghoul plague, a disease that transformed infected humans into near-mindless predatory rakghouls. At its peak, the disease infected millions of individuals, giving rise to armies of rakghouls on a number of planets. Whether rakghoul populations have persisted until this day is not known, making a rakghoul invasion on Earth not completely improbable. Further, a strategy for defence against an outbreak of the disease on Earth has not yet been proposed. To fill this glaring gap, we developed the first mathematical model of the population dynamics of humans and rakghouls during a rakghoul plague outbreak. Using New South Wales as a model site, we then obtained ensembles of model predictions for the outcome of the rakghoul plague in two different disease control strategy scenarios (population evacuation and military intervention), and in the absence thereof. Finally, based on these predictions, we propose a set of policy guidelines for successfully controlling and eliminating outbreaks of the rakghoul plague in Australian states.

  18. Recent findings regarding maintenance of enzootic variants of Yersinia pestis in sylvatic reservoirs and their significance in the evolution of epidemic plague.

    Science.gov (United States)

    Bearden, Scott W; Brubaker, Robert R

    2010-01-01

    Despite the widespread presence of bubonic plague in sylvatic reservoirs throughout the world, the causative agent (Yersinia pestis) evolved in its present form within the last 20,000 years from enteropathogenic Yersinia pseudotuberculosis. Comparison of the genomes from the two species revealed that Y. pestis possesses only a few unique plasmid-encoded genes that contribute to acute disease, whereas this organism has lost about 13% of the chromosomal genes that remain active in Y. pseudotuberculosis. These losses reflect readily detectable additions, deletions, transpositions, inversions, and acquisition of about 70 insertion sequence (IS) inserts, none of which are likely to promote increased virulence. In contrast, major enzymes of intermediary metabolism, including glucose 6-phosphate dehydrogenase (Zwf ) and aspartase, are present but not catalytically functional due to the presence of missense mutations. The latter are generally not detectable by the technology of bioinformatics and, in the case of Y. pestis, result in radical changes in the metabolic flow of carbon. As an important consequence, plague bacilli exhibit a stringent low-calcium response characterized by conversion of L-glutamate (and metabolically related amino acids) to L-aspartate with secretion of the latter into supernatant fluid at 37 degrees C in culture media containing Na(+) but lacking added Ca(2+). This phenomenon also occurs in vivo and likely adversely affects the bioenergetics of host amino acid pools. Curiously, aspartase is functional in all tested enzootic (pestoides) strains of Y. pestis. These isolates are typically restricted to the ancient plague reservoirs of Central Asia and Africa and are fully virulent in members of the rodent Superfamily Muroidea but avirulent in guinea pigs and man. The implications of these findings for the distribution and ecology of Y. pestis could be significant.

  19. Duck plague

    Science.gov (United States)

    Friend, M.

    1999-01-01

    Duck plague is caused by a herpesvirus. Infection often results in an acute, contagious, and fatal disease. As with many other herpesviruses, duck plague virus can establish inapparent infections in birds that survive exposure to it, a state referred to as latency. During latency, the virus cannot be detected by standard methods for virus isolation. Studies of domestic species of waterfowl have detected multiple strains of the virus that vary in their ability to cause disease and death. Little is known about the response of wild waterfowl to strain differences.Duck plague outbreaks are thought to be caused when birds that carry the virus shed it through fecal or oral discharge, thus releasing the virus into food and water with which susceptible birds may have contact. Experimental studies have demonstrated spontaneous virus shedding by duck plague carriers during spring. Changes in the duration of daylight and onset of breeding are thought to be physiological stresses that stimulate virus shedding at this time of year. The carriers are immune to the disease, but the virus shed by them causes infection and disease among susceptible waterfowl. Bird-to-bird contact and contact with virus that has contaminated the environment perpetuate an outbreak. Scavenging and decomposition of carcasses of infected birds also contaminate the environment by releasing viruses from tissues and body fluids. Virus transmission through the egg has been reported, but the role of the egg in the disease cycle remains to be resolved.

  20. Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

    Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

  1. 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, ...

  2. 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.

  3. DoD Global Emerging Infections Surveillance and Response System -- Partnering in the Fight Against Emerging Infections, Fiscal Year 2006

    Science.gov (United States)

    2007-02-01

    Cairo), nutritional surveys in Honduras (through NMRCD in Lima), malaria research on the Burmese border (through AFRIMS in Bangkok), and brucel - losis...collected specimens of from cases of cutaneous anthrax, bubonic plague, brucel - losis, Venezuelan equine encephalomyelitis, and Hantavirus. These

  4. [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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Exploring Other Genomes: Bacteria.

    Science.gov (United States)

    Flannery, Maura C.

    2001-01-01

    Points out the importance of genomes other than the human genome project and provides information on the identified bacterial genomes Pseudomonas aeuroginosa, Leprosy, Cholera, Meningitis, Tuberculosis, Bubonic Plague, and plant pathogens. Considers the computer's use in genome studies. (Contains 14 references.) (YDS)

  11. 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

  12. 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 to expl...

  13. 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.

  14. 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.

  15. Preliminary validation of real-time PCR assays for the identification of Yersinia pestis (Authors' personal document)

    NARCIS (Netherlands)

    Tomaso, H.; Jacobs, D.; Eickhoff, M.; Scholz, H.C.; Dahouk, S.al; Kattar, M.M.; Reischl, U.; Plicka, H.; Strand Olsen, J.; Nikkari, S.; Matero, P.; Beuret, C.; Ciammaruconi, A.; Lista, F.; Gala, J.-L.; Broll, H.; Appel, B.; Sellek Cano, R.E.; Ybarra de Villavicencio, M.d.C.; Broekhuijsen, M.P.; Indra, A.; Petersen, R.; Neubauer, H.

    2008-01-01

    Background: Yersinia pestis (Y. pestis) is a zoonotic bacterium mainly circulating among rodents and their fleas. Transmission to humans can cause bubonic, pneumonic or septicemic plague with a high case-fatality rate. Therefore, rapid and reliable diagnostic tools are crucial. The objective of this

  16. 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.

  17. Trade routes and plague transmission in pre-industrial Europe.

    Science.gov (United States)

    Yue, Ricci P H; Lee, Harry F; Wu, Connor Y H

    2017-10-11

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

  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. Inactivation of avirulent pgm+ and delta pgm Yersinia pestis by ultraviolet light (UV-C)

    Science.gov (United States)

    Yersinia pestis is the causative agent of bubonic plague. Though not considered a foodborne pathogen, Y. pestis can survive, and even grow, in some foods, and the foodborne route of transmission is not without precedent. As such, concerns exist over the possible intentional contamination of foods wi...

  20. Plague Prevention

    Science.gov (United States)

    ... visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics Info for ... or working outdoors. Products containing DEET can be applied to the skin as well as clothing and ...

  1. Interspecific comparisons of sylvatic plague in prairie dogs

    Science.gov (United States)

    Cully, J.F.; Williams, E.S.

    2001-01-01

    Of the 3 major factors (habitat loss, poisoning, and disease) that limit abundance of prairie dogs today, sylvatic plague caused by Yersinia pestis is the 1 factor that is beyond human control. Plague epizootics frequently kill >99% of prairie dogs in infected colonies. Although epizootics of sylvatic plague occur throughout most of the range of prairie dogs in the United States and are well described, long-term maintenance of plague in enzootic rodent species is not well documented or understood. We review dynamics of plague in white-tailed (Cynomys leucurus), Gunnison's (C. gunnisoni), and black-tailed (C. ludovicianus) prairie dogs, and their rodent and flea associates. We use epidemiologic concepts to support an enzootic hypothesis in which the disease is maintained in a dynamic state, which requires transmission of Y. pestis to be slower than recruitment of new susceptible mammal hosts. Major effects of plague are to reduce colony size of black-tailed prairie dogs and increase intercolony distances within colony complexes. In the presence of plague, black-tailed prairie dogs will probably survive in complexes of small colonies that are usually >3 km from their nearest neighbor colonies.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.

    Directory of Open Access Journals (Sweden)

    Wieslaw Swietnicki

    Full Text Available Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC(50 values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.

  8. Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.

    Science.gov (United States)

    Swietnicki, Wieslaw; Carmany, Daniel; Retford, Michael; Guelta, Mark; Dorsey, Russell; Bozue, Joel; Lee, Michael S; Olson, Mark A

    2011-01-01

    Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC(50) values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.

  9. 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.

  10. 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

  11. 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.

  12. Overcrowding and disease epidemics in colonial Lagos: rethinking ...

    African Journals Online (AJOL)

    Thus, it degenerated to overcrowding and disease epidemics as epitomised by the outbreak of tuberculosis and bubonic plague in 1919 and between 1924 and 1930 respectively. The paper, therefore, concludes that with the available evidence at our disposal, it is obvious that the road and railway were constructed to ...

  13. Small mammals distribution and diversity in a plague endemic area ...

    African Journals Online (AJOL)

    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 ...

  14. 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.

  15. 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.

  16. 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

  17. 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...... the landscape, such that the host population may be considered a metapopulation, with each occupied burrow system a subpopulation. We examine plague transmission within and between family groups and its effect on survival. Transmission of plague occurred disproportionately within family groups although not all...... gerbils became infected once plague entered a burrow system. There were no spatial patterns to suggest that family groups in close proximity to infected burrow systems were more at risk of infection than those far away. At one site, infection increased the chances of burrow-system extinction. Overall...

  18. 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.

  19. 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.

  20. 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.

  1. Early emergence of Yersinia pestis as a severe respiratory pathogen.

    Science.gov (United States)

    Zimbler, Daniel L; Schroeder, Jay A; Eddy, Justin L; Lathem, Wyndham W

    2015-06-30

    Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

  2. 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.

  3. 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.

  4. Efficacy of Primate Humoral Passive Transfer in a Murine Model of Pneumonic Plague Is Mouse Strain-Dependent

    Directory of Open Access Journals (Sweden)

    V. A. Graham

    2014-01-01

    Full Text Available 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.

  5. 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

  6. 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.

  7. 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.

  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. [The plague in Finland in 1710].

    Science.gov (United States)

    Engström, N G

    1994-01-01

    In the autumn of 1710 Helsinki was struck by the so-called oriental plague during four months. The infection was transferred by black rats which harboured fleas. The flea-bites caused boils. It was believed that the plague was air-borne, and the air was very humid that autumn. Big fires were lit in order to reduce the humidity, the purpose being to make it easier for the infected to breathe. Attempts were also made to dissect the boils. The carriers of the contamination came as refugees from Estland over the Gulf of Finland. The infection had spread from Turkey to Poland and Balticum after the defeat of the Finnish-Swedish army in the summer of 1709 at Poltava in Ucraine. Helsingfors (Helsinki) was struck extremely hard. About two-thirds of the inhabitants died of the pestilence. Some escaped by fleeing to the countryside. The plague spread through the country as far north as to Uleåborg (Oulu) and Cajana (Kajaani). Marketplaces became important centres of infection. With the advent of the frost in December the plague dwindled. At that time Helsinki was practically a dead town.

  10. 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

  11. [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....

  12. 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.

  13. 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.

  14. 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

  15. [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

  16. Genome-scale reconstruction of the metabolic network in Yersinia pestis CO92

    Science.gov (United States)

    Navid, Ali; Almaas, Eivind

    2007-03-01

    The gram-negative bacterium Yersinia pestis is the causative agent of bubonic plague. Using publicly available genomic, biochemical and physiological data, we have developed a constraint-based flux balance model of metabolism in the CO92 strain (biovar Orientalis) of this organism. The metabolic reactions were appropriately compartmentalized, and the model accounts for the exchange of metabolites, as well as the import of nutrients and export of waste products. We have characterized the metabolic capabilities and phenotypes of this organism, after comparing the model predictions with available experimental observations to evaluate accuracy and completeness. We have also begun preliminary studies into how cellular metabolism affects virulence.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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 ...

  3. 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.

  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. Use of an in vitro pharmacodynamic model to derive a moxifloxacin regimen that optimizes kill of Yersinia pestis and prevents emergence of resistance.

    Science.gov (United States)

    Louie, A; Heine, H S; VanScoy, B; Eichas, A; Files, K; Fikes, S; Brown, D L; Liu, W; Kinzig-Schippers, M; Sörgel, F; Drusano, G L

    2011-02-01

    Yersinia pestis, the causative agent of bubonic, septicemic, and pneumonic plague, is classified as a CDC category A bioterrorism pathogen. Streptomycin and doxycycline are the "gold standards" for the treatment of plague. However, streptomycin is not available in many countries, and Y. pestis isolates resistant to streptomycin and doxycycline occur naturally and have been generated in laboratories. Moxifloxacin is a fluoroquinolone antibiotic that demonstrates potent activity against Y. pestis in in vitro and animal infection models. However, the dose and frequency of administration of moxifloxacin that would be predicted to optimize treatment efficacy in humans while preventing the emergence of resistance are unknown. Therefore, dose range and dose fractionation studies for moxifloxacin were conducted for Y. pestis in an in vitro pharmacodynamic model in which the half-lives of moxifloxacin in human serum were simulated so as to identify the lowest drug exposure and the schedule of administration that are linked with killing of Y. pestis and with the suppression of resistance. In the dose range studies, simulated moxifloxacin regimens of ≥175 mg/day killed drug-susceptible bacteria without resistance amplification. Dose fractionation studies demonstrated that the AUC (area under the concentration-time curve)/MIC ratio predicted kill of drug-susceptible Y. pestis, while the C(max) (maximum concentration of the drug in serum)/MIC ratio was linked to resistance prevention. Monte Carlo simulations predicted that moxifloxacin at 400 mg/day would successfully treat human infection due to Y. pestis in 99.8% of subjects and would prevent resistance amplification. We conclude that in an in vitro pharmacodynamic model, the clinically prescribed moxifloxacin regimen of 400 mg/day is predicted to be highly effective for the treatment of Y. pestis infections in humans. Studies of moxifloxacin in animal models of plague are warranted.

  6. Coping with Catastrophe: The Black Death of the 14th Century. A Unit of Study for Grades 7-12.

    Science.gov (United States)

    Chapman, Anne

    This unit of study explains the causes, course, characteristics, and results of the Black Death during the 14th century. The Black Death, also known as the bubonic plague, left virtually no one untouched in Europe, Asia, and Northern Africa. Europe lost a third or more of its population. In a broader context, study of the unit alerts students to…

  7. Life style of people and surveillance of management related to cockroaches in Southern Punjab, Pakistan

    OpenAIRE

    NAEEM, Afifa; JALEEL, Waqar; SAEED, Qamar; ZAKA, Syed Muhammad; SAEED, Shafqat; NAQQASH, Muhammad Nadir; BAKHTAWAR, Marryam; AYUB, Waleed Bin

    2014-01-01

    Cockroaches are the major household pests which prefer humid areas for habitation i.e. bathrooms, kitchens, sewerage systems etc., where warmth, moisture and food are satisfactory. Cockroaches are responsible for transmitting microorganisms like pathogenic bacteria, virus and fungi. Some examples of common bacterial diseases of human beings transmitted by cockroaches are Pasteurellapestisand bubonic plague; Shigellaalkalescensand dysentery; Staphylococcus aureusand boils and abscesses; Shigel...

  8. [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.

  9. 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.

  10. 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.

  11. 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.

  12. Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago

    Science.gov (United States)

    Rasmussen, Simon; Allentoft, Morten Erik; Nielsen, Kasper; Orlando, Ludovic; Sikora, Martin; Sjögren, Karl-Göran; Pedersen, Anders Gorm; Schubert, Mikkel; Van Dam, Alex; Kapel, Christian Moliin Outzen; Nielsen, Henrik Bjørn; Brunak, Søren; Avetisyan, Pavel; Epimakhov, Andrey; Khalyapin, Mikhail Viktorovich; Gnuni, Artak; Kriiska, Aivar; Lasak, Irena; Metspalu, Mait; Moiseyev, Vyacheslav; Gromov, Andrei; Pokutta, Dalia; Saag, Lehti; Varul, Liivi; Yepiskoposyan, Levon; Sicheritz-Pontén, Thomas; Foley, Robert A.; Lahr, Marta Mirazón; Nielsen, Rasmus; Kristiansen, Kristian; Willerslev, Eske

    2015-01-01

    Summary The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics. PMID:26496604

  13. Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago

    DEFF Research Database (Denmark)

    Rasmussen, Simon; Allentoft, Morten Erik; Nielsen, Kasper

    2015-01-01

    The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asi...... genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics....... and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of...

  14. 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.

  15. 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 ...

  16. 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.

  17. Impact of Twitter intensity, time, and location on message lapse of bluebird's pursuit of fleas in Madagascar.

    Science.gov (United States)

    Da'ar, Omar B; Yunus, Faisel; Md Hossain, Nassif; Househ, Mowafa

    The recent outbreak of bubonic plague in Madagascar reminds us of the continuing public health challenges posed by such deadly diseases in various parts of the world years after their eradication. This study examines the role of Twitter in public health disease surveillance with special focus on how Twitter intensity, time, and location issues explain Twitter plague message delay. We retrospectively analyzed the Twitter feeds of the 2014 bubonic plague outbreak in Madagascar. The analyses are based on the plague-related data available in the public domain between November 19th and 27th 2014. The data were compiled in March 2015. We calculated the time differential between the tweets and retweets, and analyzed various characteristics of the Tweets including Twitter intensity of the users. A total of 6873 Twitter users were included in the study, of which 52% tweeted plague-related information during the morning hours (before mid-day), and 87% of the tweets came from the west of the epicenter of the plague. More importantly, while session of tweet lease and relative location had effect on message lapse, absolute location did not. Additionally, we found no evidence of differential effect of location on message lapse based on relative location i.e. tweets from west or east nor number of following. However, there is evidence that more intense Twitter use appears to have significant effect on message lapse such that as the number of tweets became more intense, time differential between the tweets and retweets increased while higher number of retweets diminished message lapse. This study affirms that Twitter can play an important role in ongoing disease surveillance and the timely dissemination of information during public health emergencies independent of the time and space restrictions. Further ways should be explored to embed social media channels in routine public health practice. Copyright © 2017 King Saud Bin Abdulaziz University for Health Sciences. Published by

  18. 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."

  19. 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

  20. [Plague in Zaire].

    Science.gov (United States)

    Janssens, P G; Pattyn, S R

    1994-01-01

    Two endemic foci of plague have been discovered in Zaïre, the first in the Ituri in 1928, the other in North-Kivu in 1938. They are situated in the region of the great East-African Rift and are adjacent to the Ugandan focus, identified in 1877. A strict surveillance of these endemic foci makes it possible to state that, between 1928 and 1959, 632 cases of plague have been diagnosed in the Ituri, or 20 a year, and 190 in the N-Kivu, or 8 a year. Since then several flare ups have been notified. This situation is very remote from the "black death" concept. Yersinia pestis presents, besides its bipolar staining, many other characteristics such as the indispensable presence of iron to produce virulence, or the fermentation of glycerine and reduction of nitrates as parameters for the identification of 3 biovars, corresponding with a specific geographic distribution: antiqua, medievalis, orientalis or maritima. The antigenic structure has been discussed and also the role of plasmids. Plague is a disease of rats, a variegated gathering of rodents with different degrees of tolerance and sensitiveness to Y.pestis, living in a frail equilibrium. The multimammate houserat was in the Ituri the principal agent until the black rat Rattus rattus invaded the region and a new balance came into being. The frequent changes in taxonomy of Mastomys caused uncertainties. The transmission is due to fleas subject to a blocking of their ventriculum by Y.pestis. Fleas play an active part in the process. Man is only a casual intruder. The pathogenicity is related to its invasiveness and its intracellular localization in macrophages and other R.E. cells, in which Y.pestis can survive. The bubo is characteristic of the disease. In Zaïre a septicaemic tendency has been observed, with a possible involvement of the C.N.S. and of the lungs. The latter may produce among the surrounding relatives primary pneumonic plague. The clinical diagnosis ought to be confirmed by bacteriologic investigation

  1. 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.

  2. [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.

  3. Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago.

    Science.gov (United States)

    Rasmussen, Simon; Allentoft, Morten Erik; Nielsen, Kasper; Orlando, Ludovic; Sikora, Martin; Sjögren, Karl-Göran; Pedersen, Anders Gorm; Schubert, Mikkel; Van Dam, Alex; Kapel, Christian Moliin Outzen; Nielsen, Henrik Bjørn; Brunak, Søren; Avetisyan, Pavel; Epimakhov, Andrey; Khalyapin, Mikhail Viktorovich; Gnuni, Artak; Kriiska, Aivar; Lasak, Irena; Metspalu, Mait; Moiseyev, Vyacheslav; Gromov, Andrei; Pokutta, Dalia; Saag, Lehti; Varul, Liivi; Yepiskoposyan, Levon; Sicheritz-Pontén, Thomas; Foley, Robert A; Lahr, Marta Mirazón; Nielsen, Rasmus; Kristiansen, Kristian; Willerslev, Eske

    2015-10-22

    The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

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

    DEFF Research Database (Denmark)

    Reijniers, Jonas; Davis, Stephen; Begon, Mike

    2012-01-01

    , 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...

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

    African Journals Online (AJOL)

    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 ...

  8. [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.

  9. 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.

  10. 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.

  11. Structural Insights into Ail-Mediated Adhesion in Yersinia pestis

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Satoshi; Lukacik, Petra; Barnard, Travis J.; Noinaj, Nicholas; Felek, Suleyman; Tsang, Tiffany M.; Krukonis, Eric S.; Hinnebusch, B. Joseph; Buchanan, Susan K. (Michigan); (NIH); (Michigan-Med)

    2012-01-30

    Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells.

  12. 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.

  13. [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.

  14. 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

  15. Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus

    OpenAIRE

    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

    2016-01-01

    eLife digest A bacterium called Yersina pestis is responsible for numerous human outbreaks of plague throughout history. It is carried by rats and other rodents and can spread to humans causing what we conventionally refer to as plague. The most notorious of these plague outbreaks ? the Black Death ? claimed millions of lives in Europe in the mid-14th century. Several other plague outbreaks emerged in Europe over the next 400 years. Then, there was a large gap before the plague re-emerged as ...

  16. 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.

  17. 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 ...

  18. The Formula of Plague Narratives

    DEFF Research Database (Denmark)

    Christensen, Jørgen Riber

    2015-01-01

    The article is a narratological investigation of a selection of plague tales. The selection spans millennia and different text types, technologies and genres, from The Bible to apocalyptical films, iPhone games and testimonials from Médecins Sans Frontières. The research question is whether...

  19. Plague Law or Martial Law?: Sinaloa and Baja California, 1902-1903

    Directory of Open Access Journals (Sweden)

    Ana María Carrillo

    2005-04-01

    Full Text Available This paper analyzes the social importance of the plague epidemic that caught Sinaloa and Baja California,  Mexico, in 1902 and 1903. It describes the health campaign  that was organized, the first one —in Mexico— based on the recent scientific fields of microbiology, immunology and tropical medicine.  It was also the first one in which a state turned control of sanitary activities in to the federal government. The author shows that in this campaign, health personnel  and political authorities used persuasion and, above all, compulsion, and describes how the population resisted the health measures. She analyzes the contradictions between the different actors of the campaign, explains the causes of its success and points  out  that the 1902-1903 campaign against plague became a model for further health campaigns in Mexico.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. The first case record of a female patient with bubonic lymphogranuloma venereum (LGV), serovariant L2b.

    Science.gov (United States)

    Verweij, Stephan P; Ouburg, Sander; de Vries, Harry; Morré, Servaas A; van Ginkel, Cees J W; Bos, Hanna; Sebens, Fré W

    2012-08-01

    Since 2003, a lymphogranuloma venereum epidemic has been reported in The Netherlands and other European countries. This epidemic is caused by Chlamydia trachomatis serovariant L2b and has only been seen in men having sex with men. The authors investigated a woman presenting with a bubo in her right groin. The authors showed by real-time PCR that the woman was infected with C trachomatis, serovariant L2b. This is the first reported case study of a female patient with bubonic lymphogranuloma venereum caused by serovariant L2b, which was probably contracted via her bisexual male partner.

  8. [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

  9. Critical Factors for Parameterisation of Disease Diagnosis Modelling for Anthrax, Plague and Smallpox

    Science.gov (United States)

    2012-09-01

    which could potentially differentiate the occurrence of a bio - weapon induced illness from the more common and prevailing endemic diseases that show... weapon of choice by terrorists to inflict casualties and disrupt daily life of the general populace. The Amerithrax incident has highlighted the...are no widely available rapid diagnostic tests for plague. A rapid antigen detection of soluble F1 capsular antigen in many clinical specimens of

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

    OpenAIRE

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

    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...

  11. The Impact of the Black Death on the Golden Horde: Politics, Economy, Society, Civilization

    Directory of Open Access Journals (Sweden)

    Uli Schamiloglu

    2017-06-01

    Full Text Available Research objectives and materials: This essay offers an overview of the political, economic, social, and cultural consequences of the Black Death (the epidemic of bubonic plague cause by the bacteria Yersinia pestis in the territories of the Golden Horde in the 14th–15th centuries. It considers the framework which has been developed for medieval Europe and the Middle East. It considers whether there was a medieval growth in population in the Golden Horde prior to the arrival of the Black Death in the mid-14th century. It considers the level of depopulation and how it led to political instability. It notes how bubonic plague was used as a weapon by the Mongol armies. It considers economic consequences such as the decline in certain professions and crafts, the threat to the food supply, and the rising cost of labor which led to inflation. It also considers the social crisis brought about by the sudden death of substantial portions of the population. Results and novelty of the research: The rise in urbanization in the 13th to mid-14th century was followed by a collapse in the population and decline in urban centers beginning in the second half of the 14th century. The Black Death also led to population pressure as most sedentary centers declined, while at the same time certain sedentary areas escaped the plague, as could many nomadic populations who were less susceptible to disease. It also examines the decline in literary languages and the growth in religiosity. Finally, it considers the recovery in the population beginning in the mid-15th century.

  12. YopP-expressing variant of Y. pestis activates a potent innate immune response affording cross-protection against yersiniosis and tularemia [corrected].

    Directory of Open Access Journals (Sweden)

    Ayelet Zauberman

    Full Text Available Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+P that over-expresses Y. enterocolitica YopP. When this strain was administered subcutaneously to mice, it elicited a fast and effective protective immune response in models of bubonic, pneumonic and septicemic plague. In the present study, we further characterized the immune response induced by the Kim53ΔJ+P recombinant strain. Using a panel of mouse strains defective in specific immune functions, we observed the induction of a prompt protective innate immune response that was interferon-γ dependent. Moreover, inoculation of mice with Y. pestis Kim53ΔJ+P elicited a rapid protective response against secondary infection by other bacterial pathogens, including the enteropathogen Y. enterocolitica and the respiratory pathogen Francisella tularensis. Thus, the development of new therapies to enhance the innate immune response may provide an initial critical delay in disease progression following the exposure to highly virulent bacterial pathogens, extending the time window for successful treatment.

  13. 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.

  14. [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

  15. 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

  16. 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.

  17. A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918

    Directory of Open Access Journals (Sweden)

    Egan Joseph R

    2010-10-01

    Full Text Available Abstract Background Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century. Methods The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed Rminor, and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR. Results 2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI = {57%, 98%}. For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD = 1.2 days and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days. Rminor was calculated to be 0.9 (SD = 1.0 and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%} and 20% (95% CI = {1%, 72%}, respectively. Conclusions The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague.

  18. [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

  19. Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia

    Directory of Open Access Journals (Sweden)

    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.

  20. Further development of raccoon poxvirus-vectored vaccines against plague (Yersinia pestis)

    Science.gov (United States)

    Rocke, Tonie E.; Iams, Keith P.; Dawe, S.; Smith, Susan; Williamson, Judy L.; Heisey, Dennis M.; Osorio, Jorge 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.

  1. 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

  2. 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)....

  3. 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

  4. Plague epizootic cycles in Central Asia.

    Science.gov (United States)

    Reijniers, Jonas; Begon, Mike; Ageyev, Vladimir S; Leirs, Herwig

    2014-06-01

    Infection thresholds, widely used in disease epidemiology, may operate on host abundance and, if present, on vector abundance. For wildlife populations, host and vector abundances often vary greatly across years and consequently the threshold may be crossed regularly, both up- and downward. Moreover, vector and host abundances may be interdependent, which may affect the infection dynamics. Theory predicts that if the relevant abundance, or combination of abundances, is above the threshold, then the infection is able to spread; if not, it is bound to fade out. In practice, though, the observed level of infection may depend more on past than on current abundances. Here, we study the temporal dynamics of plague (Yersinia pestis infection), its vector (flea) and its host (great gerbil) in the PreBalkhash region in Kazakhstan. We describe how host and vector abundances interact over time and how this interaction drives the dynamics of the system around the infection threshold, consequently affecting the proportion of plague-infected sectors. We also explore the importance of the interplay between biological and detectability delays in generating the observed dynamics.

  5. Findings of bacterial microflora in piglets infected with conventional swine plague

    Directory of Open Access Journals (Sweden)

    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.

  6. [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.

  7. Socio-epidemiological determinants of 2002 plague outbreak in Himachal Pradesh, India: a qualitative study

    Science.gov (United States)

    2014-01-01

    Background This qualitative investigation was conducted to determine the socio-epidemiological factors related to the plague outbreak (2002) in Himachal Pradesh (HP), India. Methods 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. Results 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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 age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults (P ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from 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.

  14. 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.

  15. 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

  16. 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.

  17. Ten years of surveillance of the Yulong plague focus in China and the molecular typing and source tracing of the isolates.

    Science.gov (United States)

    Wang, Peng; Shi, Liyuan; Zhang, Fuxin; Guo, Ying; Zhang, Zhikai; Tan, Hongli; Cui, Zhigang; Ding, Yibo; Liang, Ying; Liang, Yun; Yu, Dongzheng; Xu, Jianguo; Li, Wei; Song, Zhizhong

    2018-03-01

    Plague, caused by Yersinia pestis, was classified as a reemerging infectious disease by the World Health Organization. The five human pneumonic plague cases in Yulong County in 2005 gave rise to the discovery of a Yulong plague focus in Yunnan province, China. Thereafter, continuous wild rodent plague (sylvatic plague) was identified as the main plague reservoir of this focus. In this study, the epizootics in Yulong focus were described, and three molecular typing methods, including the different region (DFR) analysis, clustered regularly interspaced short palindromic repeats (CRISPRs), and the multiple-locus variable number of tandem repeats (VNTR) analysis (MLVA) (14+12), were used for the molecular typing and source tracing of Y. pestis isolates in the Yulong plague focus. Simultaneously, several isolates from the vicinity of Yunnan were used as controls. The results showed that during the 10-year period from 2006 to 2016, an animal plague epidemic occurred in 6 of those years, and 5 villages underwent an animal plague epidemic within a 30-km2 area of the Yulong plague focus. Searching for dead mice was the most effective monitoring method in this plague focus. No positive sample has been found in 6937 captured live rodents thus far, suggesting that the virulence of strains in the Yulong plague focus is stronger and the survival time of mice is shorter after infection. Strains from Lijiang, Sichuan and Tibet were of the same complex based on a typing analysis of DFR and CRISPR. The genetic relationship of Y. pestis illustrated by MLVA "14+12" demonstrates that Tibet and Sichuan strains evolved from the strains 1.IN2 (Qinghai, 1970 and Tibet, 1976), and Lijiang strains are closer to Batang strains (Batang County in Sichuan province, 2011, Himalaya marmot plague foci) in terms of genetic or phylogenic relationships. In conclusion, we have a deeper understanding of this new plague focus throughout this study, which provides a basis for effective prevention and

  18. Dangers of noncritical use of historical plague databases

    NARCIS (Netherlands)

    Roosen, J.; Curtis, D.R.

    2018-01-01

    Researchers have published several articles using historical data sets on plague epidemics using impressive digital databases that contain thousands of recorded outbreaks across Europe over the past several centuries. Through the digitization of preexisting data sets, scholars have unprecedented

  19. Three days in October of 1630: detailed examination of mortality during an early modern plague epidemic in Venice.

    Science.gov (United States)

    Ell, S R

    1989-01-01

    The epidemiology of medieval and early modern European plague remains highly controversial. It now seems likely that the epidemiology was not uniform throughout either the geographic or temporal boundaries of the plague in Western Europe. The Venetian plague of 1630 was extensively documented; day-by-day records were kept, and each mortality in the city was recorded in a set format. The days 23-25 October 1630, representing a period when mortality was beginning to increase sharply, are examined. In all, 1,163 deaths were recorded. They show a large preponderance of women; a mean age of 28, but a majority of cases clumped between ages 0 and 25 years; and an unequal sex ratio among children. Further, there was an identifiable smallpox epidemic raging simultaneously with plague, and more than one-quarter of all the deaths in this period of high mortality were clearly due to nonplague causes. Deaths due to wounds and associated with violence were prominent in one parish, which suggests that in times of plague the breakdown in the normal machinery of government, in everyday patterns of life, and possibly of mental well being resulted in an even more exaggerated death toll. These factors--violence, accidents, and other epidemics--have never been so definitively tied to a European plague epidemic. In addition, there are hints that plague has a marked proclivity to kill pregnant women--their deaths far outnumber those anticipated--and that plague was very localized at a given moment within Venice itself, even during times of peak mortality.

  20. [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

  1. Identification of New Virulence Factors and Vaccine Candidates for Yersinia pestis.

    Science.gov (United States)

    Andersson, Jourdan A; Sha, Jian; Erova, Tatiana E; Fitts, Eric C; Ponnusamy, Duraisamy; Kozlova, Elena V; Kirtley, Michelle L; Chopra, Ashok K

    2017-01-01

    Earlier, we reported the identification of new virulence factors/mechanisms of Yersinia pestis using an in vivo signature-tagged mutagenesis (STM) screening approach. From this screen, the role of rbsA , which encodes an ATP-binding protein of ribose transport system, and vasK , an essential component of the type VI secretion system (T6SS), were evaluated in mouse models of plague and confirmed to be important during Y. pestis infection. However, many of the identified genes from the screen remained uncharacterized. In this study, in-frame deletion mutants of ypo0815, ypo2884, ypo3614-3168 (cyoABCDE) , and ypo1119-1120 , identified from the STM screen, were generated. While ypo0815 codes for a general secretion pathway protein E (GspE) of the T2SS, the ypo2884 -encoded protein has homology to the βγ crystallin superfamily, cyoABCDE codes for the cytochrome o oxidase operon, and the ypo1119-1120 genes are within the Tol-Pal system which has multiple functions. Additionally, as our STM screen identified three T6SS-associated genes, and, based on in silico analysis, six T6SS clusters and multiple homologs of the T6SS effector hemolysin-coregulated protein (Hcp) exist in Y. pestis CO92, we also targeted these T6SS clusters and effectors for generating deletion mutants. These deletion mutant strains exhibited varying levels of attenuation (up to 100%), in bubonic or pneumonic murine infection models. The attenuation could be further augmented by generation of combinatorial deletion mutants, namely Δ lpp Δ ypo0815 , Δ lpp Δ ypo2884 , Δ lpp Δ cyoABCDE , Δ vasK Δ hcp6 , and Δ ypo2720-2733 Δ hcp3 . We earlier showed that deletion of the lpp gene, which encodes Braun lipoprotein (Lpp) and activates Toll-like receptor-2, reduced virulence of Y. pestis CO92 in murine models of bubonic and pneumonic plague. The surviving mice infected with Δ lpp Δ cyoABCDE , Δ vasK Δ hcp6 , and Δ ypo2720-2733 Δ hcp3 mutant strains were 55-100% protected upon subsequent re

  2. Identification of New Virulence Factors and Vaccine Candidates for Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Jourdan A. Andersson

    2017-10-01

    Full Text Available Earlier, we reported the identification of new virulence factors/mechanisms of Yersinia pestis using an in vivo signature-tagged mutagenesis (STM screening approach. From this screen, the role of rbsA, which encodes an ATP-binding protein of ribose transport system, and vasK, an essential component of the type VI secretion system (T6SS, were evaluated in mouse models of plague and confirmed to be important during Y. pestis infection. However, many of the identified genes from the screen remained uncharacterized. In this study, in-frame deletion mutants of ypo0815, ypo2884, ypo3614-3168 (cyoABCDE, and ypo1119-1120, identified from the STM screen, were generated. While ypo0815 codes for a general secretion pathway protein E (GspE of the T2SS, the ypo2884-encoded protein has homology to the βγ crystallin superfamily, cyoABCDE codes for the cytochrome o oxidase operon, and the ypo1119-1120 genes are within the Tol-Pal system which has multiple functions. Additionally, as our STM screen identified three T6SS-associated genes, and, based on in silico analysis, six T6SS clusters and multiple homologs of the T6SS effector hemolysin-coregulated protein (Hcp exist in Y. pestis CO92, we also targeted these T6SS clusters and effectors for generating deletion mutants. These deletion mutant strains exhibited varying levels of attenuation (up to 100%, in bubonic or pneumonic murine infection models. The attenuation could be further augmented by generation of combinatorial deletion mutants, namely ΔlppΔypo0815, ΔlppΔypo2884, ΔlppΔcyoABCDE, ΔvasKΔhcp6, and Δypo2720-2733Δhcp3. We earlier showed that deletion of the lpp gene, which encodes Braun lipoprotein (Lpp and activates Toll-like receptor-2, reduced virulence of Y. pestis CO92 in murine models of bubonic and pneumonic plague. The surviving mice infected with ΔlppΔcyoABCDE, ΔvasKΔhcp6, and Δypo2720-2733Δhcp3 mutant strains were 55–100% protected upon subsequent re-challenge with wild

  3. 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.

  4. 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.

  5. Mechanism study on a plague outbreak driven by the construction of a large reservoir in southwest china (surveillance from 2000-2015.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2017-03-01

    Full Text Available 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.

  6. 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.

  7. Wildlife Plague Surveillance Near the China-Kazakhstan Border: 2012-2015.

    Science.gov (United States)

    Zhao, S-S; Pulati, Y; Yin, X-P; Li, W; Wang, B-J; Yang, K; Chen, C-F; Wang, Y-Z

    2017-12-01

    Plague is a zoonotic disease caused by the bacterium Yersinia pestis. This pathogen can be transmitted by fleas and has an enzootic cycle, circulating among small mammals, and occasionally epizootic cycles, infecting other species. In China, infected wild rodents are primarily reservoirs of Y. Pestis and are related to human infection (Int. J. Infect. Dis., 33, 2015 and 67; BMC Microbiol., 9, 2009 and 205). Because shepherd dogs prey on and eat rodents (e.g. marmots and mice), they are valuable sentinel animals for plague serosurveillance in endemic disease foci, although their infections are usually asymptomatic (Vet. Microbiol., 172, 2014 and 339). © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  8. Small-Scale Die-Offs in Woodrats Support Long-Term Maintenance of Plague in the U.S. Southwest.

    Science.gov (United States)

    Kosoy, Michael; Reynolds, Pamela; Bai, Ying; Sheff, Kelly; Enscore, Russell E; Montenieri, John; Ettestad, Paul; Gage, Kenneth

    2017-09-01

    Our longitudinal study of plague dynamics was conducted in north-central New Mexico to identify which species in the community were infected with plague, to determine the spatial and temporal patterns of the dynamics of plague epizootics, and to describe the dynamics of Yersinia pestis infection within individual hosts. A total of 3156 fleas collected from 535 small mammals of 8 species were tested for Y. pestis DNA. Nine fleas collected from six southern plains woodrats (Neotoma micropus) and from one rock squirrel (Otospermophilus variegatus) were positive for the pla gene of Y. pestis. None of 127 fleas collected from 17 woodrat nests was positive. Hemagglutinating antibodies to the Y. pestis-specific F1 antigen were detected in 11 rodents of 6 species. All parts of the investigated area were subjected to local disappearance of woodrats. Despite the active die-offs, some woodrats always were present within the relatively limited endemic territory and apparently were never exposed to plague. Our observations suggest that small-scale die-offs in woodrats can support maintenance of plague in the active U.S. Southwestern focus.

  9. [Mechanisms of power in disease: the case of the novel "The Plague" by Albert Camus].

    Science.gov (United States)

    Hernández-Mansilla, José Miguel

    2009-01-01

    This paper explores the elements of power that can be found in an epidemic like the plague. To undertake this task we first studied, the form of containment of the plague from a historical perspective and then, compare them with those described by Camus in his novel The Plague. We also studied the experience of sin among humans in an effort to determine divine power. This last point explores the fear of being touched during an epidemic and how this is overcome by the innate feeling of love among men. Finally in the novel, this is illustrated by the love of Orpheus for Eurydice.

  10. Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th-Century Alghero, Sardinia

    Science.gov (United States)

    Benedictow, Ole Jørgen; Fornaciari, Gino; Giuffra, Valentina

    2013-01-01

    Plague, a zoonotic disease caused by the bacterium Yersinia pestis, has been responsible for at least 3 pandemics. During 1582–1583, a plague outbreak devastated the seaport of Alghero in Sardinia. By analyzing contemporary medical texts and local documentation, we uncovered the pivotal role played by the Protomedicus of Alghero, Quinto Tiberio Angelerio (1532–1617), in controlling the epidemic. Angelerio imposed rules and antiepidemic measures new to the 16th-century sanitary system of Sardinia. Those measures undoubtedly spared the surrounding districts from the spread of the contagion. Angelerio seems to have been an extremely successful public health officer in the history of plague epidemics in Sardinia. PMID:23968598

  11. 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

  12. [Epidemics and risk factors of plague in Junggar Basin, Xinjiang Uygur Autonomous Region, 2007-2016].

    Science.gov (United States)

    Zhang, Y J; Wang, C; Luo, T; Guo, R; Meng, W W

    2017-10-10

    Objective: To explore the epidemic situation of animal plague in Junggar Basin natural plague foci. Methods: Data on epidemics of plague and on population involved, as well as results on antibodies and pathogens, were analyzed. Samples on animals and vectors were collected from 18 counties in Junggar Basin plague natural foci between 2007 and 2016. Results: The density of Rhombomys (R.) opimus was temporally fluctuant, from 2.1/hm(2) to 22.6/hm(2) respectively. However, the spatial distribution appeared asymmetrical, with the highest seen in Kelamayi and Wumuqi-midong counties, as 14.2/hm(2) and 13.0/hm(2) respectively. Rates of capture on nocturnal rodents were from 4.2 % to 10.1 % , with the highest rate as 10.1 % in 2014. Meriones meridianus appeared the dominant species in the nocturnal community of rodents, which accounted for 81.9 % . Regarding the spatial and temporal distributions, rates of R. opimus with fleas appeared fluctuant, with an average rate as 90.7 % and the average total flea index was 10.44. In flea community of R. opimus , Xenopsylla (X.) skrjabini was found the dominant species, popular in distribution and accounted for 47.8 % . The average rate of nocturnal rodents with flea was 20.2 % , with total flea index as 1.20 and the dominant fleas were X. conformis conformis and Nosopsyllus laeviceps . A total of 13 species with 9 087 serum samples from rodents were detected as having Y. pestis antibody by IHA, with 617 positive samples. Of them, the positive rate of having R. opimus appeared the highest (9.4 % ), followed by D. sagitta (1.1 % ). Spatially, two clustered areas were found, with one in the eastern Junggar Basin from Changji to Mulei county, with the antibody positive rates of R. opimus as 14.3 % . The other one was in the central area of Junggar Basin, including Kelamayi, Shawan and Wusu counties, with the antibody positive rate as 13.6 % . The prevalence of plague on R. opimus was fluctuant, with the lowest seen in 2008, with the

  13. Predicting small mammal and flea abundance using landform and soil properties in a plague endemic area in Lushoto District, Tanzania.

    Science.gov (United States)

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

    2014-07-01

    Small mammals particularly rodents, are considered the primary natural hosts of plague. Literature suggests that plague persistence in natural foci has a root cause in soils. The objective of this study was to investigate the relationship between on the one hand landforms and associated soil properties, and on the other hand small mammals and fleas in West Usambara Mountains in Tanzania, a plague endemic area. Standard field survey methods coupled with Geographical Information System (GIS) technique were used to examine landform and soils characteristics. Soil samples were analysed in the laboratory for physico-chemical properties. Small mammals were trapped on pre-established landform positions and identified to genus/species level. Fleas were removed from the trapped small mammals and counted. Exploration of landform and soil data was done using ArcGIS Toolbox functions and descriptive statistical analysis. The relationships between landforms, soils, small mammals and fleas were established by generalised linear regression model (GLM) operated in R statistics software. Results show that landforms and soils influence the abundance of small mammals and fleas and their spatial distribution. The abundance of small mammals and fleas increased with increase in elevation. Small mammal species richness also increases with elevation. A landform-soil model shows that available phosphorus, slope aspect and elevation were statistically significant predictors explaining richness and abundance of small mammals. Fleas' abundance and spatial distribution were influenced by hill-shade, available phosphorus and base saturation. The study suggests that landforms and soils have a strong influence on the richness and evenness of small mammals and their fleas' abundance hence could be used to explain plague dynamics in the area.

  14. New alternatives on the control of plagues in the handling of the residuals in agricultural products

    International Nuclear Information System (INIS)

    Mendez Buenaventura, L.

    1995-01-01

    A recount of the historical evolution of the agriculture is made in the country and the use of agricultural inputs with tendency to the mono cultivations that drove to a biological imbalance and the escalation of the plagues in the main cultivations, that which forced to the integrated handling of plagues. The strategies are described using in the control integrated as they are: the use of the adverse environmental factors to the plagues, the use of the natural enemies, the cultural practices, the use of traps, the employment of resistant varieties and measures of legal type

  15. [Origin of the plague microbe Yersinia pestis: structure of the process of speciation].

    Science.gov (United States)

    Suntsov, V V

    2012-01-01

    The origin and evolution of the plague microbe Yersinia pestis are considered in the context of propositions of modern Darwinism. It was shown that the plague pathogen diverged from the pseudotuberculous microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan: 22000-15000 years ago. Speciation occurred in the tarbagan (Marmota sibirica)--flea (Oropsylla silantiewi) parasitic system. The structure of the speciation process included six stages: isolation, genetic drift, enhancement of intrapopulational polymorphism, the beginning of pesticin synthesis (genetic conflict and emergence of hiatus), specialization (stabilization of characteristics), and adaptive irradiation (transformation of the monotypic species Y. pestis tarbagani into a polytypic species). The scenario opens up wide prospects for construction of the molecular phylogeny of the plague microbe Y. pestis and for investigation of the biochemical and molecular-genetic aspects of "Darwinian" evolution of pathogens from many other nature-focal infections.

  16. Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity.

    Science.gov (United States)

    McConnell, Joseph R; Wilson, Andrew I; Stohl, Andreas; Arienzo, Monica M; Chellman, Nathan J; Eckhardt, Sabine; Thompson, Elisabeth M; Pollard, A Mark; Steffensen, Jørgen Peder

    2018-05-29

    Lead pollution in Arctic ice reflects midlatitude emissions from ancient lead-silver mining and smelting. The few reported measurements have been extrapolated to infer the performance of ancient economies, including comparisons of economic productivity and growth during the Roman Republican and Imperial periods. These studies were based on sparse sampling and inaccurate dating, limiting understanding of trends and specific linkages. Here we show, using a precisely dated record of estimated lead emissions between 1100 BCE and 800 CE derived from subannually resolved measurements in Greenland ice and detailed atmospheric transport modeling, that annual European lead emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion, accelerated during expanded Carthaginian and Roman mining primarily in the Iberian Peninsula, and reached a maximum under the Roman Empire. Emissions fluctuated synchronously with wars and political instability particularly during the Roman Republic, and plunged coincident with two major plagues in the second and third centuries, remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead-silver mining in ancient economies. Our results indicate sustained economic growth during the first two centuries of the Roman Empire, terminated by the second-century Antonine plague.

  17. A Storytelling Approach: Insights from the Shambaa.

    Science.gov (United States)

    Lamanna, Camillo

    2018-03-19

    Narrative medicine explores the stories that patients tell; this paper, conversely, looks at some of the stories that patients are told. The paper starts by examining the 'story' told by the Shambaa people of Tanzania to explain the bubonic plague and contrasts this with the stories told by Ghanaian communities to explain lymphatic filariasis. By harnessing insights from memory studies, these stories' memorability is claimed to be due to their use mnemonic devices woven into stories. The paper suggests that stories can be unpatronising, informative, and appropriate vehicles for communicating medical information to all age groups across all cultures.

  18. Vector control improves survival of three species of prairie dogs (Cynomys) in areas considered enzootic for plague

    Science.gov (United States)

    Biggins, Dean E.; Godbey, Jerry L.; Gage, Kenneth L.; Carter, Leon G.; Montenieri, John A.

    2010-01-01

    Plague causes periodic epizootics that decimate populations of prairie dogs (PDs) (Cynomys), but the means by which the causative bacterium (Yersinia pestis) persists between epizootics are poorly understood. Plague epizootics in PDs might arise as the result of introductions of Y. pestis from sources outside PD colonies. However, it remains possible that plague persists in PDs during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between their colonies. If this is true, application of vector control to reduce flea numbers might reduce mortality among PDs. To test whether vector control enhances PD survival in the absence of obvious plague epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96–98% (1 month posttreatment) on 15 areas involving three species of PDs (Cynomys leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during 2000–2004 using deltamethrin dust delivered into burrows as a pulicide. Even during years without epizootic plague, PD survival rates at dusted sites were 31–45% higher for adults and 2–34% higher for juveniles compared to survival rates at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested (6882 total fleas) and antibodies against Y. pestis were identified in serum samples from 40 of 2631 PDs. Although other explanations are possible, including transmission of other potentially fatal pathogens by fleas, ticks, or other ectoparasites, our results suggest that plague might be maintained indefinitely in PD populations in the absence of free epizootics and widespread mortality among these animals. If PDs and their fleas support enzootic cycles of plague transmission, there would be important implications for the conservation of these animals and other species.

  19. 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

  20. Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda.

    Science.gov (United States)

    Respicio-Kingry, Laurel B; Yockey, Brook M; Acayo, Sarah; Kaggwa, John; Apangu, Titus; Kugeler, Kiersten J; Eisen, Rebecca J; Griffith, Kevin S; Mead, Paul S; Schriefer, Martin E; Petersen, Jeannine M

    2016-02-01

    Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease. During January 2004-December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution. We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk.

  1. Observations on the endemicity of plague in Karatu and Ngorongoro, northern Tanzania.

    Science.gov (United States)

    Kilonzo, B S; Mbise, T J; Mwalimu, D C; Kindamba, L

    2006-01-01

    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 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. Of the rodents, 14.5% were infested with fleas, which comprised of Xenopsylla brasiliensis (45.8%) and Dinopsyllus lypusus (54.2%), with an overall population density of 0.2 fleas/animal. Thirty one (72.1%) of the dogs were infested with fleas, all of which were Ctenocephalides spp. Thirty five (63.3%) houses were infested with fleas whose population was composed of Ctenocephalides spp, Pulex irritans, Tunga penetrans and Echinophaga gallinacea. Infected rodents were found in all the villages while the infected dog was found at Rhotia-Kati. Nineteen (11%) of the rodents and one (2%) dog harboured specific plague antibodies. It was broadly concluded that sylvatic plague was endemic in Karatu district and Ngorongoro Conservation Area and that outbreaks of the disease can occur in the area any time if and when relevant conditions become favourable. Prompt application of appropriate preventive and control measures and survey for substantiating the status in the Lake Manyara National Park, which is adjacent to some of the infected villages, are recommended.

  2. 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.

  3. Plague cycles in two rodent species from China: Dry years might provide context for epizootics in wet years

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.; Xu, Lei; Liu, Qiyong

    2016-01-01

    Plague, a rodent-associated, flea-borne zoonosis, is one of the most notorious diseases in history. Rates of plague transmission can increase when fleas are abundant. Fleas commonly desiccate and die when reared under dry conditions in laboratories, suggesting fleas will be suppressed during droughts in the wild, thus reducing the rate at which plague spreads among hosts. In contrast, fleas might increase in abundance when precipitation is plentiful, producing epizootic outbreaks during wet years. We tested these hypotheses using a 27-yr data set from two rodents in Inner Mongolia, China: Mongolian gerbils (Meriones unguiculatus) and Daurian ground squirrels (Spermophilus dauricus). For both species of rodents, fleas were most abundant during years preceded by dry growing seasons. For gerbils, the prevalence of plague increased during wet years preceded by dry growing seasons. If precipitation is scarce during the primary growing season, succulent plants decline in abundance and, consequently, herbivorous rodents can suffer declines in body condition. Fleas produce more offspring and better survive when parasitizing food-limited hosts, because starving animals tend to exhibit inefficient behavioral and immunological defenses against fleas. Further, rodent burrows might buffer fleas from xeric conditions aboveground during dry years. After a dry year, fleas might be abundant due to the preceding drought, and if precipitation and succulent plants become more plentiful, rodents could increase in density, thereby creating connectivity that facilitates the spread of plague. Moreover, in wet years, mild temperatures might increase the efficiency at which fleas transmit the plague bacterium, while also helping fleas to survive as they quest among hosts. In this way, dry years could provide context for epizootics of plague in wet years.

  4. 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 hospital records kept since 1986 to describe the temporal, spatial and demographic variation in human plague. A seasonal peak in cases occurs from December to February with the numbers of cases during this peak varying between 0 and 1150. Variation in incidence, calculated for each village as the mean...... number of cases per thousand inhabitants per year, indicates that human plague is concentrated around a group of three neighbouring, relatively isolated, high-altitude villages; Nywelo, Madala and Gologolo. However, there was no evidence that these villages were acting as a source of infection...

  5. Crystallization of the acyl-CoA thioesterase TesB from Yersinia pestis

    International Nuclear Information System (INIS)

    Swarbrick, Crystall M. D.; Patterson, Edward I.; Forwood, Jade K.

    2013-01-01

    The expression, purification, crystallization and diffraction of the acyl-CoA thioesterase TesB from Y. pestis are reported. X-ray crystallographic diffraction data to 2.0 Å resolution were collected at the Australian Synchrotron. Yersinia pestis is a highly virulent human pathogen and is the causative agent of bubonic plague. Spread through the bite of infected fleas, plague epidemics have marked important events in history, including the Justinian plague (6th century), the Black Death (14th century) which decimated nearly one quarter of the European population, and more recently the Orientalis plague (1894). To date, deaths are still being reported and, without treatment, the disease kills most people within 4 days. One of the thioesterases from Y. pestis, TesB, is a broad-range acyl-CoA thioesterase and is highly conserved within prokaryotes and throughout evolution, sharing sequence similarity with the HIV Nef binding protein ACOT8. Here the expression, purification, crystallization and diffraction of TesB are reported. TesB has been recombinantly expressed and crystallized using the vapour-diffusion hanging-drop technique at pH 7.0 and 290 K. After optimization, crystals diffracted to 2.0 Å resolution at the Australian Synchrotron and belong to the space group P12 1 1 (a = 73.55, b = 170.82, c = 101.98 Å), with eight molecules likely to be present in the asymmetric unit

  6. 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.

  7. 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

  8. [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.

  9. Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

    Science.gov (United States)

    Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

    2016-11-11

    Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in Yersinia pestis [corrected].

    Directory of Open Access Journals (Sweden)

    Christopher N LaRock

    Full Text Available The etiologic agent of bubonic plague, Yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. Though the closely related enteric pathogen Y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in Y. pestis has been unclear. In this study we performed transcriptional profiling experiments to identify Y. pestis quorum sensing regulated functions. Our analysis revealed that acyl-homoserine lactone-based quorum sensing controls the expression of several metabolic functions. Maltose fermentation and the glyoxylate bypass are induced by acyl-homoserine lactone signaling. This effect was observed at 30°C, indicating a potential role for quorum sensing regulation of metabolism at temperatures below the normal mammalian temperature. It is proposed that utilization of alternative carbon sources may enhance growth and/or survival during prolonged periods in natural habitats with limited nutrient sources, contributing to maintenance of plague in nature.

  11. Integrating land cover and terrain characteristics to explain plague ...

    African Journals Online (AJOL)

    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 ...

  12. Novel CTL epitopes identified through a Y. pestis proteome-wide analysis in the search for vaccine candidates against plague.

    Science.gov (United States)

    Zvi, Anat; Rotem, Shahar; Zauberman, Ayelet; Elia, Uri; Aftalion, Moshe; Bar-Haim, Erez; Mamroud, Emanuelle; Cohen, Ofer

    2017-10-20

    The causative agent of Plague, Yersinia pestis, is a highly virulent pathogen and a potential bioweapon. Depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. The latter has a high fatality rate. In the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the F1 and LcrV antigens are currently under clinical trials. It is well known that a cellular immune response might have an essential additive value to immunity and protection against Y. pestis infection. Nevertheless, very few documented epitopes eliciting a protective T-cell response have been reported. Here, we present a combined high throughput computational and experimental effort towards identification of CD8 T-cell epitopes. All 4067 proteins of Y. pestis were analyzed with state-of-the-art recently developed prediction algorithms aimed at mapping potential MHC class I binders. A compilation of the results obtained from several prediction methods revealed a total of 238,000 peptide candidates, which necessitated downstream filtering criteria. Our previously established and proven approach for enrichment of true positive CTL epitopes, which relies on mapping clusters rich in tandem or overlapping predicted MHC binders ("hotspots"), was applied, as well as considerations of predicted binding affinity. A total of 1532 peptides were tested for their ability to elicit a specific T-cell response by following the production of IFNγ from splenocytes isolated from vaccinated mice. Altogether, the screen resulted in 178 positive responders (11.8%), all novel Y. pestis CTL epitopes. These epitopes span 113 Y. pestis proteins. Substantial enrichment of membrane-associated proteins was detected for epitopes selected from hotspots of predicted MHC binders. These results considerably expand the repertoire of known CTL epitopes in Y. pestis and pave the way to

  13. The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar.

    Science.gov (United States)

    Rahelinirina, Soanandrasana; Rajerison, Minoarisoa; Telfer, Sandra; Savin, Cyril; Carniel, Elisabeth; Duplantier, Jean-Marc

    2017-11-01

    Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

  14. 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

  15. 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 (χ 2 = 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.

  16. [Plague outbreaks in the Mediterranean area during the 2nd World War, epidemiology and treatments].

    Science.gov (United States)

    Mafart, B; Brisou, P; Bertherat, E

    2004-11-01

    Before the Second World War, the plague was still rife in North Africa but occurred only as sporadic cases or small outbreaks as in Egypt or Morocco. The permanent foci of infected wild rodent were the cause of these rural outbreaks. In 1943 and 1944, plague came back in several Mediterranean towns and ports and was considered as a serious danger for the Allied Forces. These resurgences were related to the World War as well as the overpopulation of the cities, regroupings and population movements, relaxation of prophylactic measures of the plague in sea transport. The Allied Forces medical officers then showed the resistance of Yersinia pestis to penicillin which they had been supplied with recently, the effectiveness of sulphamides but mortality remained high (27%). In parallel, the drastic fight against rodents and fleas (DDT) gave excellent results.

  17. The Asian house shrew Suncus murinus as a reservoir and source of human outbreaks of plague in Madagascar.

    Directory of Open Access Journals (Sweden)

    Soanandrasana Rahelinirina

    2017-11-01

    Full Text Available Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

  18. Typing methods for the plague pathogen, Yersinia pestis.

    Science.gov (United States)

    Lindler, Luther E

    2009-01-01

    Phenotypic and genotypic methodologies have been used to differentiate the etiological agent of plague, Yersinia pestis. Historically, phenotypic methods were used to place isolates into one of three biovars based on nitrate reduction and glycerol fermentation. Classification of Y. pestis into genetic subtypes is problematic due to the relative monomorphic nature of the pathogen. Resolution into groups is dependent on the number and types of loci used in the analysis. The last 5-10 years of research and analysis in the field of Y. pestis genotyping have resulted in a recognition by Western scientists that two basic types of Y. pestis exist. One type, considered to be classic strains that are able to cause human plague transmitted by the normal flea vector, is termed epidemic strains. The other type does not typically cause human infections by normal routes of infection, but is virulent for rodents and is termed endemic strains. Previous classification schemes used outside the Western hemisphere referred to these latter strains as Pestoides varieties of Y. pestis. Recent molecular analysis has definitely shown that both endemic and epidemic strains arose independently from a common Yersinia pseudotuberculosis ancestor. Currently, 11 major groups of Y. pestis are defined globally.

  19. Multiple mechanisms of transmission of the Caribbean coral disease white plague

    Science.gov (United States)

    Clemens, E.; Brandt, M. E.

    2015-12-01

    White plague is one of the most devastating coral diseases in the Caribbean, and yet important aspects of its epidemiology, including how the disease transmits, remain unknown. This study tested potential mechanisms and rates of transmission of white plague in a laboratory setting. Transmission mechanisms including the transport of water, contact with macroalgae, and predation via corallivorous worms and snails were tested on the host species Orbicella annularis. Two of the tested mechanisms were shown to transmit disease: water transport and the corallivorous snail Coralliophila abbreviata. Between these transmission mechanisms, transport of water between a diseased coral and a healthy coral resulted in disease incidence significantly more frequently in exposed healthy corals. Transmission via water transport also occurred more quickly and was associated with higher rates of tissue loss (up to 3.5 cm d-1) than with the corallivorous snail treatment. In addition, water that was in contact with diseased corals but was filtered with a 0.22-μm filter prior to being introduced to apparently healthy corals also resulted in the transmission of disease signs, but at a much lower rate than when water was not filtered. This study has provided important information on the transmission potential of Caribbean white plague disease and highlights the need for a greater understanding of how these processes operate in the natural environment.

  20. Comparative scaffolding and gap filling of ancient bacterial genomes applied to two ancient Yersinia pestis genomes

    Science.gov (United States)

    Doerr, Daniel; Chauve, Cedric

    2017-01-01

    Yersinia pestis is the causative agent of the bubonic plague, a disease responsible for several dramatic historical pandemics. Progress in ancient DNA (aDNA) sequencing rendered possible the sequencing of whole genomes of important human pathogens, including the ancient Y. pestis strains responsible for outbreaks of the bubonic plague in London in the 14th century and in Marseille in the 18th century, among others. However, aDNA sequencing data are still characterized by short reads and non-uniform coverage, so assembling ancient pathogen genomes remains challenging and often prevents a detailed study of genome rearrangements. It has recently been shown that comparative scaffolding approaches can improve the assembly of ancient Y. pestis genomes at a chromosome level. In the present work, we address the last step of genome assembly, the gap-filling stage. We describe an optimization-based method AGapEs (ancestral gap estimation) to fill in inter-contig gaps using a combination of a template obtained from related extant genomes and aDNA reads. We show how this approach can be used to refine comparative scaffolding by selecting contig adjacencies supported by a mix of unassembled aDNA reads and comparative signal. We applied our method to two Y. pestis data sets from the London and Marseilles outbreaks, for which we obtained highly improved genome assemblies for both genomes, comprised of, respectively, five and six scaffolds with 95 % of the assemblies supported by ancient reads. We analysed the genome evolution between both ancient genomes in terms of genome rearrangements, and observed a high level of synteny conservation between these strains. PMID:29114402

  1. Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th-Century Alghero, Sardinia

    OpenAIRE

    Bianucci, Raffaella; Benedictow, Ole J?rgen; Fornaciari, Gino; Giuffra, Valentina

    2013-01-01

    Plague, a zoonotic disease caused by the bacterium Yersinia pestis, has been responsible for at least 3 pandemics. During 1582?1583, a plague outbreak devastated the seaport of Alghero in Sardinia. By analyzing contemporary medical texts and local documentation, we uncovered the pivotal role played by the Protomedicus of Alghero, Quinto Tiberio Angelerio (1532?1617), in controlling the epidemic. Angelerio imposed rules and antiepidemic measures new to the 16th-century sanitary system of Sardi...

  2. Identifying the social and environmental determinants of plague endemicity in Peru: insights from a case study in Ascope, La Libertad.

    Science.gov (United States)

    Rivière-Cinnamond, Ana; Santandreu, Alain; Luján, Anita; Mertens, Frederic; Espinoza, John Omar; Carpio, Yesenia; Bravo, Johnny; Gabastou, Jean-Marc

    2018-02-06

    Plague remains a public health problem in specific areas located in Bolivia, Brazil, Ecuador and Peru. Its prevention and control encompasses adequate clinical management and timely laboratory diagnosis. However, understanding communities' interaction with its surrounding ecosystem as well as the differences between community members and institutional stakeholders regarding the root causes of plague might contribute to understand its endemicity. We aim at bridging the traditionally separate biological and social sciences by elucidating communities' risk perception and identifying knowledge gaps between communities and stakeholders. This approach has been used in other areas but never in understanding plague endemicity, nor applied in the Latin American plague context. The objectives were to identify (i) plague risk perception at community level, (ii) perceived social and environmental determinants of plague endemicity, and (iii) institutions that need to be involved and actions needed to be taken as proposed by stakeholders and community members. The study was performed in 2015 and took place in Ascope rural province, La Libertad Region, in Peru, where the study areas are surrounded by intensive private sugarcane production. We propose using a multi-level discourse analysis. Community households were randomly selected (n = 68). Structured and semi-structured questionnaires were applied. A stakeholder analysis was used to identify policy makers (n = 34). In-depth interviews were performed, recorded and transcribed. Descriptive variables were analyzed with SPSS®. Answers were coded following variables adapted from the Commission on Social Determinants of Health and analyzed with the assistance of ATLAS.ti®. Results showed that risk perception was low within the community. Policy-makers identified agriculture and sugarcane production as the root cause while community answers ranked the hygiene situation as the main cause. Stakeholders first ranked

  3. 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.

  4. [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. ,

  5. 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 (7.7×104 LD50). 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.

  6. Vegetation habitats and small mammals in a plague endemic area ...

    African Journals Online (AJOL)

    Keywords: plague, vegetation, habitats, rodents distribution, Tanzania ... diseases (Eisen et al., 2007), and for the development of pest management .... This study received approval from Directorate of Research and Post-Graduate Studies of ..... be explained by the nature of human activities including grazing, bush fires, fire.

  7. Deltamethrin flea-control preserves genetic variability of black-tailed prairie dogs during a plague outbreak

    Science.gov (United States)

    Jones, P.H.; Biggins, D.E.; Eads, D.A.; Eads, S.L.; Britten, H.B.

    2012-01-01

    Genetic variability and structure of nine black-tailed prairie dog (BTPD, Cynomys ludovicianus) colonies were estimated with 15 unlinked microsatellite markers. A plague epizootic occurred between the first and second years of sampling and our study colonies were nearly extirpated with the exception of three colonies in which prairie dog burrows were previously dusted with an insecticide, deltamethrin, used to control fleas (vectors of the causative agent of plague, Yersinia pestis). This situation provided context to compare genetic variability and structure among dusted and non-dusted colonies pre-epizootic, and among the three dusted colonies pre- and post-epizootic. We found no statistical difference in population genetic structures between dusted and non-dusted colonies pre-epizootic. On dusted colonies, gene flow and recent migration rates increased from the first (pre-epizootic) year to the second (post-epizootic) year which suggested dusted colonies were acting as refugia for prairie dogs from surrounding colonies impacted by plague. Indeed, in the dusted colonies, estimated densities of adult prairie dogs (including dispersers), but not juveniles (non-dispersers), increased from the first year to the second year. In addition to preserving BTPDs and many species that depend on them, protecting colonies with deltamethrin or a plague vaccine could be an effective method to preserve genetic variability of prairie dogs. ?? 2011 Springer Science+Business Media B.V.

  8. Investigation of vesicle-capsular plague antigen complex formation by elastic laser radiation scattering

    Science.gov (United States)

    Guseva, N. P.; Maximova, Irina S.; Romanov, Sergey V.; Shubochkin, L. P.; Tatarintsev, Sergey N.

    1991-05-01

    Recently a great deal of attention has been given to the investigation artificial lipid liposomes, due to their application as "containers" for directed transport of biologically active compounds into particular cells, organs and tissues for prophylaxis and therapy of infectious diseases. The use of traditional methods of liposome investigation, such as sedimentation, electrophoresis and chromatography is impeded by low liposome resistivity to different deformations. In conjunction with this, optical methods of laser light scattering are promising as they allow nondisturbing, precise and quick investigations. This paper describes the investigation of vesicle systems prepared from egg lecithin of Serva Corporation and their complexes with the capsular antigen of the plague microbe. The capsular antigen Fl was obtained from EV plague microbe grown at 37° C on Huttinger agar. Fl was isolated by gel-filtration on ASA-22 followed by freeze drying of the preparation. Angular dependences of polarized radiation scattering were measured for several liposome suspension samples in a saline solution before and after the interaction with the plague microbe capsular antigen. The aim of the investigation was to analyze the nature of mutual antigen arrangement in a liposome and to develop methods for measuring its inclusion percentage.

  9. 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.

  10. Detections of Yersinia pestis East of the Known Distribution of Active Plague in the United States.

    Science.gov (United States)

    Mize, Erica L; Britten, Hugh B

    2016-02-01

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

  11. Investigating the ?Trojan Horse? Mechanism of Yersinia pestis Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McCutchen-Maloney, S L; Fitch, J P

    2005-02-08

    Yersinia pestis, the etiological agent of plague, is a Gram-negative, highly communicable, enteric bacterium that has been responsible for three historic plague pandemics. Currently, several thousand cases of plague are reported worldwide annually, and Y. pestis remains a considerable threat from a biodefense perspective. Y. pestis infection can manifest in three forms: bubonic, septicemic, and pneumonic plague. Of these three forms, pneumonic plague has the highest fatality rate ({approx}100% if left untreated), the shortest intervention time ({approx}24 hours), and is highly contagious. Currently, there are no rapid, widely available vaccines for plague and though plague may be treated with antibiotics, the emergence of both naturally occurring and potentially engineered antibiotic resistant strains makes the search for more effective therapies and vaccines for plague of pressing concern. The virulence mechanism of this deadly bacterium involves induction of a Type III secretion system, a syringe-like apparatus that facilitates the injection of virulence factors, termed Yersinia outer membrane proteins (Yops), into the host cell. These virulence factors inhibit phagocytosis and cytokine secretion, and trigger apoptosis of the host cell. Y. pestis virulence factors and the Type III secretion system are induced thermally, when the bacterium enters the mammalian host from the flea vector, and through host cell contact (or conditions of low Ca{sup 2+} in vitro). Apart from the temperature increase from 26 C to 37 C and host cell contact (or low Ca{sup 2+} conditions), other molecular mechanisms that influence virulence induction in Y. pestis are largely uncharacterized. This project focused on characterizing two novel mechanisms that regulate virulence factor induction in Y. pestis, immunoglobulin G (IgG) binding and quorum sensing, using a real-time reporter system to monitor induction of virulence. Incorporating a better understanding of the mechanisms of virulence

  12. 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 ...

  13. 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.

  14. 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.

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

    African Journals Online (AJOL)

    have been exposed to Yersinia pestis, the plague pathogen, in the recent past. Since home range of rodents is known to be fairly short as previously demonstrated in Muheza, Morogoro and Lushoto districts (Kilonzo, 1984; Leirs, 1992; R.H. Makundi, unpubl.), the current observations can be justifiably interpreted to suggest ...

  16. Transmission efficiency of the plague pathogen (Y. pestis) by the flea, Xenopsylla skrjabini, to mice and great gerbils.

    Science.gov (United States)

    Zhang, Yujiang; Dai, Xiang; Wang, Qiguo; Chen, Hongjian; Meng, Weiwei; Wu, Kemei; Luo, Tao; Wang, Xinhui; Rehemu, Azhati; Guo, Rong; Yu, Xiaotao; Yang, Ruifu; Cao, Hanli; Song, Yajun

    2015-05-01

    Plague, a zoonotic disease caused by Yersinia pestis, is characterized by its ability to persist in the plague natural foci. Junggar Basin plague focus was recently identified in China, with Rhombomys opimus (great gerbils) and Xenopsylla skrjabini as the main reservoir and vector for plague. No transmission efficiency data of X. skrjabini for Y. pestis is available till now. In this study, we estimated the median infectious dose (ID50) and the blockage rates of X. skrjabini with Y. pestis, by using artificial feeders. We then evaluated the flea transmission ability of Y. pestis to the mice and great gerbils via artificial bloodmeal feeding. Finally, we investigated the transmission of Y. pestis to mice with fleas fed by infected great gerbils. ID50 of Y. pestis to X. skrjabini was estimated as 2.04 × 10(5) CFU (95% CI, 1.45 × 10(5) - 3.18 × 10(5) CFU), around 40 times higher than that of X. cheopis. Although fleas fed by higher bacteremia bloodmeal had higher infection rates for Y. pestis, they lived significantly shorter than their counterparts. X. skrjabini could get fully blocked as early as day 3 post of infection (7.1%, 3/42 fleas), and the overall blockage rate of X. cheopis was estimated as 14.9% (82/550 fleas) during the 14 days of investigation. For the fleas infected by artificial feeders, they seemed to transmit plague more efficiently to great gerbils than mice. Our single flea transmission experiments also revealed that, the transmission capacity of naturally infected fleas (fed by infected great gerbils) was significantly higher than that of artificially infected ones (fed by artificial feeders). Our results indicated that ID50 of Y. pestis to X. skrjabini was higher than other fleas like X. cheopis, and its transmission efficiency to mice might be lower than other flea vectors in the artificial feeding modes. We also found different transmission potentials in the artificially infected fleas and the naturally infected ones. Further studies are

  17. 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

  18. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission--Colorado, June-July 2014.

    Science.gov (United States)

    Runfola, Janine K; House, Jennifer; Miller, Lisa; Colton, Leah; Hite, Donna; Hawley, Alex; Mead, Paul; Schriefer, Martin; Petersen, Jeannine; Casaceli, Colleen; Erlandson, Kristine M; Foster, Clayton; Pabilonia, Kristy L; Mason, Gary; Douglas, John M

    2015-05-01

    On July 8, 2014, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified Yersinia pestis, the bacterium that causes plague, in a blood specimen collected from a man (patient A) hospitalized with pneumonia. The organism had been previously misidentified as Pseudomonas luteola by an automated system in the hospital laboratory. An investigation led by Tri-County Health Department (TCHD) revealed that patient A's dog had died recently with hemoptysis. Three other persons who had contact with the dog, one of whom also had contact with patient A, were ill with fever and respiratory symptoms, including two with radiographic evidence of pneumonia. Specimens from the dog and all three human contacts yielded evidence of acute Y. pestis infection. One of the pneumonia cases might have resulted through human-to-human transmission from patient A, which would be the first such event reported in the United States since 1924. This outbreak highlights 1) the need to consider plague in the differential diagnosis of ill domestic animals, including dogs, in areas where plague is endemic; 2) the limitations of automated diagnostic systems for identifying rare bacteria such as Y. pestis; and 3) the potential for milder plague illness in patients taking antimicrobial agents. Hospital laboratorians should be aware of the limitations of automated identification systems, and clinicians should suspect plague in patients with clinically compatible symptoms from whom P. luteola is isolated.

  19. The role and significance of Luo Zhiyuan's Shu yi hui bian in the history of plague in Lingnan (south of the five ridges).

    Science.gov (United States)

    Li, H; Lai, W

    1999-04-01

    Being the earliest monograph on plague in China, Luo Zhiyuan's Shu yi hui bian, not included in the National Catalogue of TCM Books, include the following contents: personal idea on the etiology of plague; Luo's friend Wu Xuanchang' unpublished Shu yu zhi fa on the treatment and manifestations of plague; Luo's specific recipe for plague based on medified Wang Qingren's Jie du huo xue decoction based on Wang Qingrens yi lin gai cuo; therapy for critical cases; many therapies applied on Lingnan, including experimental recipes, external therapy, preventive methods, and preventing recurrence methods; Luo's special administrating methods, including persisting day-and-night method, immediate persisting method, single-dose persisting method, and double-dose persisting method. He also gave several cured case records. His book, featuring unique idea with good effect, was repeatedly printed and extensively distributed, exerting influence, more or less, on the plague monographs of later ages, and occupying important position in the history of plague on Lingnan and the whole country as well. His idea of "that poisons and static blood" in pathogenesis and therapeutic principle of antitoxicity and activating blood is coincided with the results of present day clinical and laboratory studies. His administration of medicines is heuristic to the therapy of critical cases with Chinese medicaments and to the recognition of pathogenesis, etiology, and treatment of modern plague as well as other diseases of similar etiology and pathognesis and is worth of further study.

  20. Discovery of a leptospirosis cluster amidst a pneumonic plague outbreak in a miners' camp in the Democratic Republic of the Congo.

    Science.gov (United States)

    Bertherat, Eric; Mueller, Melissa J; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-02-07

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa.

  1. 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.

  2. Did medieval trade activity and a viral etiology control the spatial extent and seasonal distribution of Black Death mortality?

    Science.gov (United States)

    Bossak, Brian H; Welford, Mark R

    2009-06-01

    Recent research into the world's greatest recorded epidemic, the Medieval Black Death (MBD), has cast doubt on Bubonic Plague as the etiologic agent. Prior research has recently culminated in outstanding advances in our understanding of the spatio-temporal pattern of MBD mortality, and a characterization of the incubation, latent, infectious, and symptomatic periods of the MBD. However, until now, several mysteries remained unexplained, including perhaps the biggest quandary of all: why did the MBD exhibit inverse seasonal peaks in mortality from diseases recorded in modern times, such as seasonal Influenza or the Indian Plague Epidemics of the early 1900 s? Although some have argued that climate changes likely explain the observed differences between modern clinical Bubonic Plague seasonality and MBD mortality accounts, we believe that another factor explains these dissimilarities. Here, we provide a synthetic hypothesis which builds upon previous theories developed in the last ten years or so. Our all-encompassing theory explains the causation, dissemination, and lethality of the MBD. We theorize that the MBD was a human-to-human transmitted virus, originating in East-Central Asia and not Africa (as some recent work has proposed), and that its areal extent during the first great epidemic wave of 1347-1350 was controlled hierarchically by proximity to trade routes. We also propose that the seasonality of medieval trade controlled the warm-weather mortality peaks witnessed during 1347-1350; during the time of greatest market activity, traders, fairgoers, and religious pilgrims served as unintentional vectors of a lethal virus with an incubation period of approximately 32 days, including a largely asymptomatic yet infectious period of roughly three weeks. We include a description of the rigorous research agenda that we have proposed in order to subject our theory to scientific scrutiny and a description of our plans to generate the first publicly available

  3. [History of human epidemic and endemic diseases in the southwest Indian Ocean].

    Science.gov (United States)

    Gaüzère, B-A; Aubry, P

    2013-05-01

    Smallpox has been known in the Mascarene Islands since 1729, and in 1898, the vaccinogenic and anti-rabies Institute of Tananarive, the future Pasteur Institute of Madagascar, was created to combat it. Cholera first arrived in the Mascarenes in 1819, but did not affect the Comoros Islands and Madagascar until the current pandemic. Bubonic plague has beset the ports of Madagascar and the Mascarenes since 1898. Girard and Robic developed the anti-plague vaccine in 1931 at the Pasteur Institute of Madagascar. The Mascarenes lost their reputation as Eden when malaria arrived in 1841, and this disease remains prominent in Madagascar and Comoros. Leprosy has been known in La Réunion since 1726 and is still very present in Mayotte, Anjouan, and Madagascar. Leptospirosis is a public health problem, except in Madagascar and the Comoros. Dengue, chikungunya, and Rift Valley fever are also present. HIV/AIDS is not a major concern, except in Mauritius, where it was spread by injection drug use, in the Seychelles and in Madagascar's largest cities. Madagascar is the principal site worldwide of chromoblastomycosis, first described there in 1914.

  4. [All around the deathbed of Lubbert ten Busch. The Modern Devotion and the plague in Deventer in 1398].

    Science.gov (United States)

    Mertens, T

    1999-01-01

    The seriousness of plague epidemics can be expressed in numbers and medical terms, but we get closer to the past, and it becomes our own history more than in any other way, when we can empathise with the story of a single individual. In the summer months of 1398, the plague raged in the city of Deventer, which lies on the river IJssel, in the east of the present-day Netherlands. This plague epidemic also threatened the small community of priests and minor clerics which gave rise to the new spiritual movement of the Modern Devotion. This new community was concerned about its survival. Their vocation required that the brethren should help the citizens who remained behind. However, this could prove to be their undoing, and therefore it would be better to leave the city. They resolved the dilemma by dividing into two groups. Half of the brethren left to ensure the continuity of the community; the other half stayed in Deventer to help the people. The two groups stayed in contact by means of letters, the text of which has survived in several sources. The fears and forebodings became reality. The plague also affected the new community of brethren. The deputy rector, Lubbert ten Busch, also died of the plague. There is a letter from him which he wrote just before he died. This farewell letter was sent together with a letter from one of the brethren, saying that Lubbert had meanwhile died, and describing the scene of his death. Because of the personal tone and the tragic of content, the letters about the death of Lubbert ten Busch are unique medieval documents. They give a good insight into the way in which the plague could personally affect someone and his immediate companions in the late Middle Ages. This paper focuses attention on these letters, and reconstructs the events around this death, so that the letters speak to us once again.

  5. 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.

  6. Public health challenges and emerging diseases: the case of São Paulo

    Directory of Open Access Journals (Sweden)

    Silva Luiz Jacintho da

    2001-01-01

    Full Text Available The author discusses the challenges posed by emerging infectious diseases in 100 years of public health in the state of São Paulo, Brazil. With an advanced and organized public health system, São Paulo responded to the emergence of infectious diseases by creating research institutions and control programs. The late 19th century witnessed the first modern research institution in microbiology, in response to the bubonic plague. A changing economy led to constant changes in ecosystems. The late 20th century presents a wide array of both emerging and rapidly changing infectious diseases. The present situation calls for creative solutions. Ecosystem analysis and more agile epidemiological surveillance are seen as the best alternatives.

  7. FLEAS OF BLACK-FOOTED FERRETS (MUSTELA NIGRIPES) AND THEIR POTENTIAL ROLE IN THE MOVEMENT OF PLAGUE.

    Science.gov (United States)

    Mize, Erica L; Grassel, Shaun M; Britten, Hugh B

    2017-07-01

    Sylvatic plague is one of the major impediments to the recovery of the black-footed ferret ( Mustela nigripes ) because it decimates their primary prey species, prairie dogs ( Cynomys spp.), and directly causes mortality in ferrets. Fleas are the primary vector of Yersinia pestis , the causative agent of sylvatic plague. The goal of this research was to better understand the flea fauna of ferrets and the factors that might influence flea abundance on ferrets. Fleas from ferrets were tested for Y. pestis in a post hoc assessment to investigate the plausibility that some ferrets could act as incidental transporter hosts of fleas infected with Y. pestis . Fleas were collected from ferrets captured on the Lower Brule Indian Reservation in central South Dakota, US from 2009 to 2012. A total of 528 fleas collected from 67 individual ferrets were identified and tested for the presence of Y. pestis with a nested PCR assay. The predominant flea recovered from ferrets was Oropsylla hirsuta , a species that comprises 70-100% of the fleas recovered from prairie dogs and their burrows in the study area. Yersinia pestis was detected at low levels in fleas collected from ferrets with prevalence ranging from 0% to 2.9%; male ferrets harbored significantly more fleas than female ferrets. Six of 67 ferrets vaccinated against plague carried fleas that tested positive for Y. pestis , which suggests ferrets vaccinated against plague could inadvertently act as incidental transporter hosts of Y. pestis -positive fleas.

  8. Analysis of temperature-dependent changes in the metabolism of Yersinia pestis.

    Science.gov (United States)

    Navid, Ali; Almaas, Eivind

    2008-03-01

    The gram-negative bacterium Yersinia pestis is the aetiological agent of bubonic plague, a zoonotic infection that occurs through the bite of a flea. It has long been known that Y. pestis has different metabolic needs upon transition from the flea gut environment (26 C) to that of a mammalian host (37 C). To study this and other outstanding questions about metabolic function of Y. pestis, we used the available genomic, biochemical and physiological data to develop a constraint-based flux balance model of metabolism in the avirulent 91001 strain (biovar Mediaevalis) of this organism. Utilizing two sets of whole-genome DNA microarray expression data, we examined the system level changes that occur when Y. pestis acclimatizes to temperature shifts. Our results point to fundamental changes in its oxidative metabolism of sugars and use of amino acids, in particular that of arginine. This behavior is indicative of an inefficient metabolism that could be caused by adaptation to life in a nutrient rich environment.

  9. Discovery of a Leptospirosis Cluster Amidst a Pneumonic Plague Outbreak in a Miners’ Camp in the Democratic Republic of the Congo

    Science.gov (United States)

    Bertherat, Eric; Mueller, Melissa J.; Shako, Jean-Christophe; Picardeau, Mathieu

    2014-01-01

    Conditions in the Democratic Republic of the Congo provide an ideal environment for leptospirosis and plague, both of which can cause severe pulmonary manifestations. In December 2004, an outbreak of lethal pneumonia occurred in a local mining camp, affecting 130 persons and killing 57 of them. Clinical signs, fast disease spread, and initial laboratory investigations suggested pneumonic plague. While leptospirosis had not recently been described in the region, it was considered as a differential diagnosis. Anti-Leptospira antibodies were detected by microscopic agglutination test (MAT). A confirmed case of leptospirosis was defined as having consistent clinical signs and any one of the following: seroconversion or four-fold increase in MAT titre for paired serum samples, or a MAT titre ≥ 1:400 for acute-phase serum samples. Twenty-nine of the 54 patients or convalescents tested for leptospirosis were seropositive. Two cases showed a confirmed infection for both plague and leptospirosis. While evidence supports the plague nature of this outbreak, the results suggest that some of the suspected plague cases might be due to leptospirosis. In any case, this diagnosis will have to be evoked in the future if a similar outbreak occurs in this region of Africa. PMID:24514425

  10. 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.

  11. 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.

  12. 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

    2011-01-01

    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. PMID:21423736

  13. A recombinant raccoon poxvirus vaccine expressing both Yersinia pestis F1 and truncated V antigens protects animals against lethal plague.

    Science.gov (United States)

    Rocke, Tonie E.; Kingstad-Bakke, B; Berlier, W; Osorio, J.E.

    2014-01-01

    In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307-a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis.. The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas.

  14. 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.

  15. Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines

    Science.gov (United States)

    Tao, Pan; Mahalingam, Marthandan; Kirtley, Michelle L.; van Lier, Christina J.; Sha, Jian; Yeager, Linsey A.; Chopra, Ashok K.; Rao, Venigalla B.

    2013-01-01

    Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH2-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines. PMID:23853602

  16. Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia pestis as next generation plague vaccines.

    Directory of Open Access Journals (Sweden)

    Pan Tao

    Full Text Available Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH₂-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS. The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel and T4 decorated F1mut-V (no adjuvant provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines.

  17. 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...

  18. 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

  19. The dancing plague: a public health conundrum.

    Science.gov (United States)

    Donaldson, L J; Cavanagh, J; Rankin, J

    1997-07-01

    The phenomenon of mass, frenzied dancing affected large populations in various parts of Europe from the thirteenth century and lasted, on and off, for three centuries. The exact aetiology of the Dancing Plague (or Dancing Mania) is still unclear. Retrospective historical review of this public health problem reveals claims for causative factors including demonic possession, epilepsy, the bite of a tarantula, ergot poisoning and social adversity. It seems unlikely that Dancing Mania resulted from a single cause but rather resulted from multiple factors combining with a predisposing cultural background and triggered by adverse social circumstances. Dancing Mania remains one of the unresolved mysteries of public health.

  20. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.

    Science.gov (United States)

    Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J; Zhou, Pei; Sebbane, Florent

    2017-07-25

    The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of Lpx

  1. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

    Energy Technology Data Exchange (ETDEWEB)

    Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J.; Zhou, Pei; Sebbane, Florent; Nacy, Carol A.

    2017-07-25

    ABSTRACT

    The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effectivein vitroagainst a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacteriumYersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

    IMPORTANCEThe rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are activein vitroagainst a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad

  2. [ON THE ORIGIN OF HYPERVIRULENCE OF THE CAUSATIVE AGENT OF PLAGUE].

    Science.gov (United States)

    Anisimov, N V; Kislichkina, A A; Platonov, M E; Evseeva, V V; Kadnikova, L A; Lipatnikova, N A; Bogun, A G; Dentovskaya, S V; Anisimov, A P

    2016-01-01

    The attempt to combine Yersinia pseudotuberculosis and Yersinia pestis into one species has been unsupported by microbiologists due to the specific features of the epidemiology and clinical presentations of their induced diseases and to basic differences in their virulence. Pseudotuberculosis is predominantly a relatively mild human intestinal infection transmitted through contaminated food and plague is an acute generalized disease with high mortality, which is most frequently transmitted by the bites of infected fleas. Y. pestis hypervirulence, the ability of single bacteria to ensure the development of predagonal bacteriemia in rodents, which is sufficient to contaminate the fleas, is one of the main events during pathogen adaptation to a new ecological niche. By analyzing the data of molecular typing of the representative kits of naturally occurring Y. pestis isolates, the authois consider the issues of formation of intraspecies groups with universal hypervirulence, as well as biovars that are highly virulent only to their major host. A strategy for searching for selective virulence factors, the potential molecular targets for vaccination and etiotropic treatment of plague, is discussed.

  3. Characteristics of the repair - deficient mutants 1435 plague microbe strain

    International Nuclear Information System (INIS)

    Temiralieva, G.A.

    1977-01-01

    Repair-deficient mutants 1435 A uvr - hcr - , 1435-17 uvr - hcr + and 1435-35 lon have been obtained from 1435 plague microbe strain, isolated from a large gerbil living in the Central Asian desert region. The mutants have the same cultural-morphological and enzymatic characteristics, the same need in growth factors and similar virulence determinants as the original strain, but they do not cause death of the experimental animals

  4. 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

  5. Tularemia and plague survey in rodents in an earthquake zone in southeastern Iran

    Science.gov (United States)

    Gyuranecz, Miklós

    2015-01-01

    OBJECTIVES: Earthquakes are one the most common natural disasters that lead to increased mortality and morbidity from transmissible diseases, partially because the rodents displaced by an earthquake can lead to an increased rate of disease transmission. The aim of this study was to evaluate the prevalence of plague and tularemia in rodents in the earthquake zones in southeastern Iran. METHODS: In April 2013, a research team was dispatched to explore the possible presence of diseases in rodents displaced by a recent earthquake magnitude 7.7 around the cities of Khash and Saravan in Sistan and Baluchestan Province. Rodents were trapped near and in the earthquake zone, in a location where an outbreak of tularemia was reported in 2007. Rodent serums were tested for a serological survey using an enzyme-linked immunosorbent assay. RESULTS: In the 13 areas that were studied, nine rodents were caught over a total of 200 trap-days. Forty-eight fleas and 10 ticks were obtained from the rodents. The ticks were from the Hyalomma genus and the fleas were from the Xenopsylla genus. All the trapped rodents were Tatera indica. Serological results were negative for plague, but the serum agglutination test was positive for tularemia in one of the rodents. Tatera indica has never been previously documented to be involved in the transmission of tularemia. CONCLUSIONS: No evidence of the plague cycle was found in the rodents of the area, but evidence was found of tularemia infection in rodents, as demonstrated by a positive serological test for tularemia in one rodent. PMID:26602769

  6. SEASON OF DELTAMETHRIN APPLICATION AFFECTS FLEA AND PLAGUE CONTROL IN WHITE-TAILED PRAIRIE DOG (CYNOMYS LEUCURUS) COLONIES, COLORADO, USA.

    Science.gov (United States)

    Tripp, Daniel W; Streich, Sean P; Sack, Danielle A; Martin, Daniel J; Griffin, Karen A; Miller, Michael W

    2016-07-01

    In 2008 and 2009, we evaluated the duration of prophylactic deltamethrin treatments in white-tailed prairie dog ( Cynomys leucurus ) colonies and compared effects of autumn or spring dust application in suppressing flea numbers and plague. Plague occurred before and during our experiment. Overall, flea abundance tended to increase from May or June to September, but it was affected by deltamethrin treatment and plague dynamics. Success in trapping prairie dogs (animals caught/trap days) declined between June and September at all study sites. However, by September trap success on dusted sites (19%; 95% confidence interval [CI] 16-22%) was about 15-fold greater than on undusted control sites (1%; CI 0.3-4%; P≤0.0001). Applying deltamethrin dust as early as 12 mo prior seemed to afford some protection to prairie dogs. Our data showed that dusting even a portion of a prairie dog colony can prolong its persistence despite epizootic plague. Autumn dusting may offer advantages over spring in suppressing overwinter or early-spring flea activity, but timing should be adjusted to precede the annual decline in aboveground activity for hibernating prairie dog species. Large colony complexes or collections of occupied but fragmented habitat may benefit from dusting some sites in spring and others in autumn to maximize flea suppression in a portion of the complex or habitat year-round.

  7. Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th-Centruy Alghero, Sardinia

    Centers for Disease Control (CDC) Podcasts

    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.

  8. Contribution of land use to rodent flea load distribution in the plague ...

    African Journals Online (AJOL)

    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 ...

  9. 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.

  10. Temporal and spatial distribution characteristics in the natural plague foci of Chinese Mongolian gerbils based on spatial autocorrelation.

    Science.gov (United States)

    Du, Hai-Wen; Wang, Yong; Zhuang, Da-Fang; Jiang, Xiao-San

    2017-08-07

    The nest flea index of Meriones unguiculatus is a critical indicator for the prevention and control of plague, which can be used not only to detect the spatial and temporal distributions of Meriones unguiculatus, but also to reveal its cluster rule. This research detected the temporal and spatial distribution characteristics of the plague natural foci of Mongolian gerbils by body flea index from 2005 to 2014, in order to predict plague outbreaks. Global spatial autocorrelation was used to describe the entire spatial distribution pattern of the body flea index in the natural plague foci of typical Chinese Mongolian gerbils. Cluster and outlier analysis and hot spot analysis were also used to detect the intensity of clusters based on geographic information system methods. The quantity of M. unguiculatus nest fleas in the sentinel surveillance sites from 2005 to 2014 and host density data of the study area from 2005 to 2010 used in this study were provided by Chinese Center for Disease Control and Prevention. The epidemic focus regions of the Mongolian gerbils remain the same as the hot spot regions relating to the body flea index. High clustering areas possess a similar pattern as the distribution pattern of the body flea index indicating that the transmission risk of plague is relatively high. In terms of time series, the area of the epidemic focus gradually increased from 2005 to 2007, declined rapidly in 2008 and 2009, and then decreased slowly and began trending towards stability from 2009 to 2014. For the spatial change, the epidemic focus regions began moving northward from the southwest epidemic focus of the Mongolian gerbils from 2005 to 2007, and then moved from north to south in 2007 and 2008. The body flea index of Chinese gerbil foci reveals significant spatial and temporal aggregation characteristics through the employing of spatial autocorrelation. The diversity of temporary and spatial distribution is mainly affected by seasonal variation, the human

  11. 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...

  12. The Acridian plagues, a new Holocene and Pleistocene palaeoclimatic indicator

    Science.gov (United States)

    Meco, Joaquín; Petit-Maire, Nicole; Ballester, Javier; Betancort, Juan F.; Ramos, Antonio J. G.

    2010-07-01

    Five palaeosols, intercalated within the Quaternary dune beds of Fuerteventura and Lanzarote (Canary Islands), off the Moroccan coast, mark wetter climatic episodes. In all of them, billions of calcified insect ootheca testify to past occurrences of Acridian plagues, such as those reaching the western Sahara following heavy rainfall events over the Sahel. The most massive infestation is in the Holocene, and should coincide with the climax of Saharo-Sahelian humidity at the peak of the present interglacial.

  13. Environmental drivers of Yersinia pestis - a holistic perspective on Medieval Europe

    Science.gov (United States)

    Buentgen, U.

    2009-09-01

    Recent studies have indicated some evidence for a link between climate variability and plague (Yersinia pestis) dynamics in Central Asia and during most of the 20th century. An intensification of plague outbreaks via population peaks in its host-species, the great gerbil (Rhombomys opimus) and its fleas (Xenopsylla spp) has been found to occur during periods of warmer spring and wetter summer climate. This is important, as human epidemics of plague ultimately originate in its wildlife reservoirs. Given the fact that Medieval Europe was strongly devastated by the Black Death - the second pandemic after the Justinian plague ~540AD, and that the worldwide highest quality and quantity of climate proxy data exist for Europe, we here present, for the first time, a holistic approach to enhance understanding of the mid-14th century Black Death. This is of primary importance not only for medical/epidemiological research, but also for other scientific communities, because the Black Death disease had a sustainable impact on the socio-economic development, culture, art, and religion of Medieval Europe. Palaeoclimatic records of annually resolved European temperature and drought variability are compiled, a high-resolution time-series of anthropogenic deforestation is utilized, documentary archives of socio-economic relevance are considered, and the animal-born plague bacterium is placed in the ecological web. Considering the European/North Atlantic sector and the last millennium, periods of high solar radiation and reduced volcanic activity shift the North Atlantic Oscillation into a generally positive mode, yielding towards warmer temperatures and an intensification of the hydrological cycle. We now argue that increased internal circulation resulted in an overall wetter and warmer climate ~1350AD, which most likely was able to promote the prevalence of existing and widespread Yersinia pestis bacillus. Resulting outbreaks of bubonic plague could have been also supported by the

  14. Dynamics of the pneumonic plague epidemic in Madagascar, August to October 2017.

    Science.gov (United States)

    Tsuzuki, Shinya; Lee, Hyojung; Miura, Fuminari; Chan, Yat Hin; Jung, Sung-Mok; Akhmetzhanov, Andrei R; Nishiura, Hiroshi

    2017-11-01

    Transmission potential and severity of pneumonic plague in Madagascar were assessed. Accounting for reporting delay, the reproduction number was estimated at 1.73. The case fatality risk was estimated as 5.5%. Expected numbers of exported cases from Madagascar were estimated across the world and all estimates were below 1 person from August to October, 2017.

  15. Analysis of anthrax and plague biowarfare vaccine interactions with human monocyte-derived dendritic cells

    NARCIS (Netherlands)

    Skowera, Anna; de Jong, Esther C.; Schuitemaker, Joost H. N.; Allen, Jennifer S.; Wessely, Simon C.; Griffiths, Gareth; Kapsenberg, Martien; Peakman, Mark

    2005-01-01

    The anti-biowarfare anthrax and plague vaccines require repeated dosing to achieve adequate protection. To test the hypothesis that this limited immunogenicity results from the nature of vaccine interactions with the host innate immune system, we investigated molecular and cellular interactions

  16. Importance of intersectoral co-ordination in the control of communicable diseases, with special reference to plague in Tanzania.

    Science.gov (United States)

    Kilonzo, B S

    1994-07-01

    Human health, agriculture, including livestock, energy, education, wildlife, construction, forestry and trade sectors are inter-related and their co-ordination is an important pre-requisite for successful control of most communicable diseases including plague. Similar linkage between research, policy, training and extension activities in each sector are essential for any successful control strategy. Inadequate agricultural produce, inaccessibility of people to the available food and ignorance on proper preparation and usage of available food materials are responsible for malnutrition, and malnourished people are very vulnerable to disease. Irrigation schemes facilitate breeding of various disease vectors and transmission of some communicable diseases. Forests are ecologically favourable for some disease vectors and reservoirs for tsetse flies and rodents, while deforestation leads to soil erosion, lack of rainfall and consequently reduced productivity in agriculture which may result in poor nutrition of the population. Wildlife and livestock serve as reservoirs and/or carriers of various zoonoses including plague, trypanosomiasis and rabies. Lack of proper co-ordination of these sectors in communicable disease control programmes can result in serious and undesirable consequences. Indiscriminate killing of rodents in order to minimize food damage by these vermin forces their flea ectoparasites to seek alternative hosts, including man, a development which may result in transmission of plague from rodents to man. Similarly, avoidance of proper quarantine during plague epidemics, an undertaking which is usually aimed at maintaining economic and social links with places outside the affected focus, can result in the disease becoming widespread and consequently make any control strategies more difficult and expensive.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Phylogeny and Classification of Yersinia pestis Through the Lens of Strains From the Plague Foci of Commonwealth of Independent States

    Directory of Open Access Journals (Sweden)

    Vladimir V. Kutyrev

    2018-05-01

    Full Text Available The established phylogeny of the etiological agent of plague, Yersinia pestis, is not perfect, as it does not take into account the strains from numerous natural foci of Commonwealth of Independent States (CIS. We have carried out PCR and SNP typing of 359 strains and whole genome sequencing of 51 strains from these plague foci and determined the phylogenetic diversity of the strains circulating here. They belong to 0.ANT3, 0.ANT5, 2.ANT3, 4.ANT branches of antique biovar, 2.MED0, 2.MED1 branches of medieval biovar and to 0.PE2, 0.PE4a. 0.PE4h, 0.PE4t branches. Based on the studies of 178 strains from 23 plague foci of CIS countries, it was determined that the population structure of 2.MED strains is subdivided into Caucasian–Caspian and Central Asian–Chinese branches. In Central-Caucasian high-mountain plague foci in the Russian Federation (RF the most deeply diverged branch of medieval biovar, 2.MED0, has been found. With the data obtained, the current population structure of Y. pestis species has been refined. New subspecies classification is developed, comprising seven subspecies: pestis, caucasica (0.PE2, angolica (0.PE3, central asiatica (0.PE4, tibetica (0.PE7, ulegeica (0.PE5, and qinghaica (0.PE10.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Precipitation, Climate Change, and Parasitism of Prairie Dogs by Fleas that Transmit Plague.

    Science.gov (United States)

    Eads, David A; Hoogland, John L

    2017-08-01

    Fleas (Insecta: Siphonaptera) are hematophagous ectoparasites that can reduce the fitness of vertebrate hosts. Laboratory populations of fleas decline under dry conditions, implying that populations of fleas will also decline when precipitation is scarce under natural conditions. If precipitation and hence vegetative production are reduced, however, then herbivorous hosts might suffer declines in body condition and have weakened defenses against fleas, so that fleas will increase in abundance. We tested these competing hypotheses using information from 23 yr of research on 3 species of colonial prairie dogs in the western United States: Gunnison's prairie dog (Cynomys gunnisoni, 1989-1994), Utah prairie dog (Cynomys parvidens, 1996-2005), and white-tailed prairie dog (Cynomys leucurus, 2006-2012). For all 3 species, flea-counts per individual varied inversely with the number of days in the prior growing season with >10 mm of precipitation, an index of the number of precipitation events that might have caused a substantial, prolonged increase in soil moisture and vegetative production. Flea-counts per Utah prairie dog also varied inversely with cumulative precipitation of the prior growing season. Furthermore, flea-counts per Gunnison's and white-tailed prairie dog varied inversely with cumulative precipitation of the just-completed January and February. These results complement research on black-tailed prairie dog (Cynomys ludovicianus) and might have important ramifications for plague, a bacterial disease transmitted by fleas that devastates populations of prairie dogs. In particular, our results might help to explain why, at some colonies, epizootics of plague, which can kill >95% of prairie dogs, are more likely to occur during or shortly after periods of reduced precipitation. Climate change is projected to increase the frequency of droughts in the grasslands of western North America. If so, then climate change might affect the occurrence of plague epizootics

  3. 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.

  4. Las sombras de la política sanitaria durante el peronismo: Los brotes epidémicos en Buenos Aires

    Directory of Open Access Journals (Sweden)

    Ramacciotti, Karina Inés

    2006-12-01

    Full Text Available This article examines the social and political consequences brought on by the emergence of bubonic plague, smallpox, and poliomyelitis in the city of Buenos Aires during the Peronist decade. The different strategies used to limit the political impact of these diseases changed the direction of public health policy and modified the governmental agendas.

    Este artículo revisará las consecuencias sociales y políticas que trajo el surgimiento de la peste bubónica, la viruela y la poliomielitis en la ciudad de Buenos Aires durante la década peronista. Las diferentes estrategias utilizadas para limitar el impacto político de estas enfermedades generaron cambios de rumbos en la política sanitaria y modificaciones en las agendas gubernamentales.

  5. Resistance to Innate Immunity Contributes to Colonization of the Insect Gut by Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Shaun C Earl

    Full Text Available Yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. Bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. However prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. Here we establish a Drosophila melanogaster model system to gain insight into Y. pestis colonization of the insect vector. We show that Y. pestis establishes a stable infection in the anterior midgut of fly larvae, and we used this model system to study the roles of genes involved in biofilm production and/or resistance to gut immunity stressors. We find that PhoP and GmhA both contribute to colonization and resistance to antimicrobial peptides in flies, and furthermore, the data suggest biofilm formation may afford protection against antimicrobial peptides. Production of reactive oxygen species in the fly gut, as in fleas, also serves to limit bacterial infection, and OxyR mediates Y. pestis survival in both insect models. Overall, our data establish the fruit fly as an informative model to elucidate the relationship between Y. pestis and its flea vector.

  6. The abundance threshold for plague as a critical percolation phenomenon

    DEFF Research Database (Denmark)

    Davis, S; Trapman, P; Leirs, H

    2008-01-01

    . 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....... Abundance thresholds are the theoretical basis for attempts to manage infectious disease by reducing the abundance of susceptibles, including vaccination and the culling of wildlife 6, 7, 8 . This first natural example of a percolation threshold in a disease system invites a re-appraisal of other invasion...

  7. OBESITY : A MODERN DAY PLAGUE.

    Science.gov (United States)

    Yadav, Yatendra Kumar

    2002-01-01

    Obesity is the presence of excess body fat. Unfortunately obesity is taken as a mere cosmetic problem and not a medical one. Today obesity is being 'dealt' with more by the self-proclaimed fitness experts running the rapidly mushrooming fitness centres rather than by medical professionals. But rather than merely a cosmetic problem, obesity should be viewed as a disease because there are multiple biologic hazards at surprisingly low levels of excess fat With the rapid pace of industrialisation and economic progress, today more and more jobs are becoming sedentary and dietary patterns are also changing with a decline in the cereal intake and increase in the intake of sugar and fats. However, inherited physiologic differences in response to eating and exercise are also important factors. Treating obesity can often be a frustrating experience for both the physician and the patient because of the great difficulty in maintaining weight loss over the long term. However, a clear understanding of the causes of obesity and a treatment strategy based on a combination of diet, nutrition, education, exercise, behaviour modification and social support can go a long way in containing this 'modern day plague' before it acquires epidemic proportions.

  8. 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 6 th century AD, which persisted until the 8 th century [1]; the renowned Black Death of the 14 th century [2, 3], with recurrent outbreaks until the 18 th century [4]; and the most recent 19 th 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.

  9. Droughts may increase susceptibility of prairie dogs to fleas: Incongruity with hypothesized mechanisms of plague cycles in rodents

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.; Long, Dustin H.; Gage, Kenneth L.; Antolin, Michael F.

    2016-01-01

    Plague is a reemerging, rodent-associated zoonosis caused by the flea-borne bacterium Yersinia pestis. As a vector-borne disease, rates of plague transmission may increase when fleas are abundant. Fleas are highly susceptible to desiccation under hot-dry conditions; we posited that their densities decline during droughts. We evaluated this hypothesis with black-tailed prairie dogs (Cynomys ludovicianus) in New Mexico, June–August 2010–2012. Precipitation was relatively plentiful during 2010 and 2012 but scarce during 2011, the driest spring–summer on record for the northeastern grasslands of New Mexico. Unexpectedly, fleas were 200% more abundant in 2011 than in 2010 and 2012. Prairie dogs were in 27% better condition during 2010 and 2012, and they devoted 287% more time to grooming in 2012 than in 2011. During 2012, prairie dogs provided with supplemental food and water were in 23% better condition and carried 40% fewer fleas. Collectively, these results suggest that during dry years, prairie dogs are limited by food and water, and they exhibit weakened defenses against fleas. Long-term data are needed to evaluate the generality of whether droughts increase flea densities and how changes in flea abundance during sequences of dry and wet years might affect plague cycles in mammalian hosts.

  10. [Correlative factors related to the density of Meriones unguiculatus in the Meriones unguiculatus plague foci of Hebei province, 2001-2013].

    Science.gov (United States)

    Niu, Y F; Kang, X P; Yan, D; Zhang, Y H; Liu, G; Kang, D M; Liu, H Z; Shi, X M; Li, Y G

    2016-08-10

    To explore the yearly, monthly and habitat-related distribution and their relations with Meriones unguiculatus density in the Hebei Meriones unguiculatus plague foci, from 2001 to 2013. Data related to Meriones unguiculatus was gathered through the monitoring programs set up at the national and provincial Meriones unguiculatus plague foci in Hebei province, from 2001 to 2013. According to the yearly density of Meriones unguiculatus, criteria set for the three groups under study, were as follows:'high-risk group'-when the rodent density was≥1.00 under rodents/hm(2),'warning group'-when the rodents/hm(2)>rodent density> 0.20,'standard group'-when rodents/hm(2) rodent density≤0.20 rodents/hm(2). Differences of habitats and monthly distribution among the three groups were compared, under the Kruskal-Wallis H rank sum test while their relations were under the multiple correspondence analysis. The Meriones unguiculatus densities were higher than 1.00 rodents/hm(2), far above the set national standards, in the monitoring area, between 2001 and 2005. From 2005, though the rodent densities began to decrease, however, figures from 2008 to 2013 were still among 0.20 to 1.00 rodents/hm(2). The distribution of habitats in the three groups showed that the Meriones unguiculatus densities were all different in habitats and the difference was statistically significant (Pplague increased in Hebei Meriones unguiculatus plague foci. Based on the distribution of Meriones unguiculatus, programs should be set to monitor the rodent in arable land and wasteland, in April and June, to reduce the prevalence of animals plague.

  11. Bacterial profiling of White Plague Disease across corals and oceans indicates a conserved and distinct disease microbiome

    KAUST Repository

    Roder, C.; Arif, C.; Daniels, C.; Weil, E.; Voolstra, Christian R.

    2014-01-01

    microarrays to assay differences in bacterial assemblages of healthy and diseased colonies displaying White Plague Disease (WPD) signs from two closely related Caribbean coral species, Orbicella faveolata and Orbicella franksi. Analysis of differentially

  12. 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.

  13. Fast and Simple Detection of Yersinia pestis Applicable to Field Investigation of Plague Foci

    Science.gov (United States)

    Simon, Stéphanie; Demeure, Christian; Lamourette, Patricia; Filali, Sofia; Plaisance, Marc; Créminon, Christophe; Volland, Hervé; Carniel, Elisabeth

    2013-01-01

    Yersinia pestis, the plague bacillus, has a rodent-flea-rodent life cycle but can also persist in the environment for various periods of time. There is now a convenient and effective test (F1-dipstick) for the rapid identification of Y. pestis from human patient or rodent samples, but this test cannot be applied to environmental or flea materials because the F1 capsule is mostly produced at 37°C. The plasminogen activator (PLA), a key virulence factor encoded by a Y. pestis-specific plasmid, is synthesized both at 20°C and 37°C, making it a good candidate antigen for environmental detection of Y. pestis by immunological methods. A recombinant PLA protein from Y. pestis synthesized by an Escherichia coli strain was used to produce monoclonal antibodies (mAbs). PLA-specific mAbs devoid of cross-reactions with other homologous proteins were further cloned. A pair of mAbs was selected based on its specificity, sensitivity, comprehensiveness, and ability to react with Y. pestis strains grown at different temperatures. These antibodies were used to develop a highly sensitive one-step PLA-enzyme immunoassay (PLA-EIA) and an immunostrip (PLA-dipstick), usable as a rapid test under field conditions. These two PLA-immunometric tests could be valuable, in addition to the F1-disptick, to confirm human plague diagnosis in non-endemic areas (WHO standard case definition). They have the supplementary advantage of allowing a rapid and easy detection of Y. pestis in environmental and flea samples, and would therefore be of great value for surveillance and epidemiological investigations of plague foci. Finally, they will be able to detect natural or genetically engineered F1-negative Y. pestis strains in human patients and environmental samples. PMID:23383008

  14. Comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine F1+rV270.

    Science.gov (United States)

    Qi, Zhizhen; Zhou, Lei; Zhang, Qingwen; Ren, Lingling; Dai, Ruixia; Wu, Benchuan; Wang, Tang; Zhu, Ziwen; Yang, Yonghai; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Qiu, Yefeng; Guo, Zhaobiao; Yang, Ruifu; Wang, Xiaoyi

    2010-02-10

    In this study, a new subunit vaccine that comprised native F1 and recombinant rV270 was evaluated for protective efficacy using mouse, guinea pig and rabbit models in comparison with the live attenuated vaccine EV76. Complete protection against challenging with 10(6) colony-forming units (CFU) of virulent Yersinia pestis strain 141 was observed for mice immunized with the subunit vaccines and EV76 vaccine. In contrast, the subunit vaccine recipes VII (F1-20 microg+rV270-10 microg) and IX (F1-40 microg+rV270-20 microg) and EV76 vaccine provided 86%, 79% and 93% protection against the same level of challenge in guinea pigs and 100%, 83% and 100% protection in rabbits, respectively. The immunized mice with the vaccines had significantly higher IgG titres than the guinea pigs and rabbits, and the immunized guinea pigs developed significantly higher IgG titres than the rabbits, but the anti-F1 response in guinea pigs was more variable than in the mice and rabbits, indicating that guinea pig is not an ideal model for evaluating protective efficacy of plague subunit vaccine, instead the rabbits could be used as an alternative model. All the immunized animals with EV76 developed a negligible IgG titre to rV270 antigen. Furthermore, analysis of IgG subclasses in the immunized animals showed a strong response for IgG1, whereas those receiving EV76 immunization demonstrated predominant production of IgG1 and IgG2a isotypes. The subunit vaccine and EV76 vaccine are able to provide protection for animals against Y. pestis challenge, but the subunit vaccines have obvious advantages over EV76 in terms of safety of use. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  15. Genetic variation at the MHC DRB1 locus is similar across Gunnison's prairie dog (Cynomys gunnisoni) colonies regardless of plague history

    Science.gov (United States)

    Cobble, Kacy R.; Califf, Katy J.; Stone, Nathan E.; Shuey, Megan M.; Birdsell, Dawn; Colman, Rebecca E.; Schupp, James M.; Aziz, Maliha; Van Andel, Roger; Rocke, Tonie E.; Wagner, David M.; Busch, Joseph D.

    2016-01-01

    Yersinia pestis was introduced to North America around 1900 and leads to nearly 100% mortality in prairie dog (Cynomys spp.) colonies during epizootic events, which suggests this pathogen may exert a strong selective force. We characterized genetic diversity at an MHC class II locus (DRB1) in Gunnison's prairie dog (C. gunnisoni) and quantified population genetic structure at the DRB1versus 12 microsatellite loci in three large Arizona colonies. Two colonies, Seligman (SE) and Espee Ranch (ES), have experienced multiple plague-related die-offs in recent years, whereas plague has never been documented at Aubrey Valley (AV). We found fairly low allelic diversity at the DRB1 locus, with one allele (DRB1*01) at high frequency (0.67–0.87) in all colonies. Two otherDRB1 alleles appear to be trans-species polymorphisms shared with the black-tailed prairie dog (C. ludovicianus), indicating that these alleles have been maintained across evolutionary time frames. Estimates of genetic differentiation were generally lower at the MHC locus (FST = 0.033) than at microsatellite markers (FST = 0.098). The reduced differentiation at DRB1 may indicate that selection has been important for shaping variation at MHC loci, regardless of the presence or absence of plague in recent decades. However, genetic drift has probably also influenced theDRB1 locus because its level of differentiation was not different from that of microsatellites in anFST outlier analysis. We then compared specific MHC alleles to plague survivorship in 60C. gunnisoni that had been experimentally infected with Y. pestis. We found that survival was greater in individuals that carried at least one copy of the most common allele (DRB1*01) compared to those that did not (60% vs. 20%). Although the sample sizes of these two groups were unbalanced, this result suggests the possibility that this MHC class II locus, or a nearby linked gene, could play a role in plague survival.

  16. Hfq-dependent, co-ordinate control of cyclic diguanylate synthesis and catabolism in the plague pathogen Yersinia pestis.

    Science.gov (United States)

    Bellows, Lauren E; Koestler, Benjamin J; Karaba, Sara M; Waters, Christopher M; Lathem, Wyndham W

    2012-11-01

    Yersinia pestis, the cause of the disease plague, forms biofilms to enhance flea-to-mammal transmission. Biofilm formation is dependent on exopolysaccharide synthesis and is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP), but the mechanisms by which Y. pestis regulates c-di-GMP synthesis and turnover are not fully understood. Here we show that the small RNA chaperone Hfq contributes to the regulation of c-di-GMP levels and biofilm formation by modulating the abundance of both the c-di-GMP phosphodiesterase HmsP and the diguanylate cyclase HmsT. To do so, Hfq co-ordinately promotes hmsP mRNA accumulation while simultaneously decreasing the stability of the hmsT transcript. Hfq-dependent regulation of HmsP occurs at the transcriptional level while the regulation of HmsT is post-transcriptional and is localized to the 5' untranslated region/proximal coding sequence of the hmsT transcript. Decoupling HmsP from Hfq-based regulation is sufficient to overcome the effects of Δhfq on c-di-GMP and biofilm formation. We propose that Y. pestis utilizes Hfq to link c-di-GMP levels to environmental conditions and that the disregulation of c-di-GMP turnover in the absence of Hfq may contribute to the severe attenuation of Y. pestis lacking this RNA chaperone in animal models of plague. © 2012 Blackwell Publishing Ltd.

  17. Handling of vegetable biodiversity and the biological control of insect-plague: Case of an organic vineyard

    International Nuclear Information System (INIS)

    Nicholls, Clara I

    2000-01-01

    In the handling of plagues it is feasible to increase natural enemies, populations diversifying the habitat. In the agro ecosystems the importance of the marginal vegetation is recognized for the parasitoids survival and predators. In commercial cultivations of vineyards, managed organically, was ahead this work, corridors of 65 different species from plants with flowers were settled down. The covering cultivations were sowed in array for half every year. The vineyards received 2 tons of compost on average for hectare. For the control of illnesses it was used sulfur preventively. It sought to be necessary if the corridor 200 meters long could increase the biological control of insect's plague in the vineyard. It was evaluated the contribution of the corridor like supplier of alternative nutritious resources, consistent, abundant and well distributed of natural enemies. It was proven the utility of the corridor to increase the populational levels of beneficent insects

  18. LIVING MICROORGANISM’S STABILYZATION IN BIOMASS BIOTECHNOLOGY AND PLAGUE VACCINE PREPARATION

    Directory of Open Access Journals (Sweden)

    D. A. Budika

    2016-01-01

    Full Text Available Over the years, the production release of the plague vaccine is well developed its technology. The technological cycle of production of the preparation consists of regulated steps, however, despite their effectiveness it is necessary to modernize the manufactoring process, for example, solutions for some of the pressing needs of the customers, in particular, small groups of immunization. Our research has focused on obtaining experimental samples plague vaccine smaller compared to the commercial vaccine, the number of doses per vial prepared in a biomass production unit (ACM-Sh surface by cultivation using all regulated processing steps, except step of combining content two swabs, and then an additional dilution of the cell suspension stabilizer. However, the time information and the subsequent preparation of such a vaccine is excluded us, since biomass is the second flush in quantitative terms is a ready raw material for the preparation of reduced dosage. The benefits of receiving the vaccine reduced the number of doses directly from the biomass of the second flush with the concentration of microbial cells Yersinia pestis EV 20–40 × 109 biotechnology greatly simplify the manufacture of such a preparation. The experimental vaccine series were tested by major regulated parameters: optical concentration, vitality, thermal stability, the loss on drying. In addition, the vaccine was prefabricated with high baseline viability to extreme temperatures (37±1°C for 24 hours to exclude enough viable microbial cells for subsequent stabilization indicator of viability during storage. It should be noted that all the experimental samples preserved viability index not lower regulated (25% during the experiment, in contrast to the commercial preparation. To determine the stability of the formulation during storage (over 3 years was a comparative analysis of the viability of the experimental and commercial lots. To assess post vaccination

  19. Controlling the geogrpahical spread of infectious disease: Plague in Italy, 1347- 1851

    OpenAIRE

    Cliff, Andrew D.; Smallman- Raynor, Matthew R.; Stevens, Peta M.

    2009-01-01

    After the establishment of the first quarantine station in the Republic of Ragusa (modern-day Dubrovnik) in 1377, the states and principalities of Italy developed a sophisticated system of defensive quarantine in an attempt to protect themselves from the ravages of plague. Using largely unknown and unseen historical maps, this paper reconstructs the extent and operation of the system used. It is shown that a cordon sanitaire existed around the coast of Italy for several centuries, consisting ...

  20. Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors

    NARCIS (Netherlands)

    Laayouni, H.; Oosting, M.; Luisi, P.; Ioana, M.; Alonso, S.; Ricano-Ponce, I.; Trynka, G.; Zhernakova, A.; Plantinga, T.S.; Cheng, S.C.; Meer, J.W. van der; Popp, R.; Sood, A.; Thelma, B.K.; Wijmenga, C.; Joosten, L.A.; Bertranpetit, J.; Netea, M.G.

    2014-01-01

    Recent historical periods in Europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. This study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic

  1. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA.

    Science.gov (United States)

    Tripp, Daniel W; Rocke, Tonie E; Streich, Sean P; Abbott, Rachel C; Osorio, Jorge E; Miller, Michael W

    2015-04-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  2. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA

    Science.gov (United States)

    Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.

    2015-01-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  3. Spatial distribution and ecological environment analysis of great gerbil in Xinjiang Plague epidemic foci based on remote sensing

    International Nuclear Information System (INIS)

    Gao, Mengxu; Wang, Juanle; Li, Qun; Cao, Chunxiang

    2014-01-01

    Yersinia pestis (Plague bacterium) from great gerbil was isolated in 2005 in Xinjiang Dzungarian Basin, which confirmed the presence of the plague epidemic foci. This study analysed the spatial distribution and suitable habitat of great gerbil based on the monitoring data of great gerbil from Chinese Center for Disease Control and Prevention, as well as the ecological environment elements obtained from remote sensing products. The results showed that: (1) 88.5% (277/313) of great gerbil distributed in the area of elevation between 200 and 600 meters. (2) All the positive points located in the area with a slope of 0–3 degree, and the sunny tendency on aspect was not obvious. (3) All 313 positive points of great gerbil distributed in the area with an average annual temperature from 5 to 11 °C, and 165 points with an average annual temperature from 7 to 9 °C. (4) 72.8% (228/313) of great gerbil survived in the area with an annual precipitation of 120–200mm. (5) The positive points of great gerbil increased correspondingly with the increasing of NDVI value, but there is no positive point when NDVI is higher than 0.521, indicating the suitability of vegetation for great gerbil. This study explored a broad and important application for the monitoring and prevention of plague using remote sensing and geographic information system

  4. Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

    Science.gov (United States)

    Quenee, Lauriane E.; Ciletti, Nancy A.; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

    2012-01-01

    Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing. PMID:21763383

  5. Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague.

    Directory of Open Access Journals (Sweden)

    Amy J Vogler

    2017-09-01

    Full Text Available Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the

  6. Temporal phylogeography of Yersinia pestis in Madagascar: Insights into the long-term maintenance of plague.

    Science.gov (United States)

    Vogler, Amy J; Andrianaivoarimanana, Voahangy; Telfer, Sandra; Hall, Carina M; Sahl, Jason W; Hepp, Crystal M; Centner, Heather; Andersen, Genevieve; Birdsell, Dawn N; Rahalison, Lila; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Rajerison, Minoarisoa

    2017-09-01

    Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period. We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period. Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated

  7. 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.

  8. SAP R/3 An IT-plague or the answer to the Tailors dream?

    DEFF Research Database (Denmark)

    Koch, Christian

    1999-01-01

    The IT-market of ERP-systems have significantly changed over the last 10 years. At least in Denmark manufacturing enterprises used to close "partner like" collaboration with their IT-supplier, now face mass produced packaged software. This challenges the skills of technology managers, can they cope...... with the IT-plague, do they suffer from the "power of default",i.e. the use of standard settings of parameters?- or can they tailor anything to anybody?...

  9. 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.

  10. Better modelling practice : an ontological perpsective on multidisciplinary, model-based problem solving

    NARCIS (Netherlands)

    Scholten, H.

    2008-01-01

    Mathematical models are more and more used to support to solve multidisciplinary, real world problems of increasing complexity. They are often plagued by obstacles such as miscommunication between modellers with different disciplinary backgrounds leading to a non-transparent modelling process. Other

  11. [Marcus Aurelius Antonius (121-180AD), philosopher and Roman emperor, and Galen's plague].

    Science.gov (United States)

    Muñoz-Sanz, Agustín

    2012-11-01

    The study of the aetiologies of diseases in Ancient Times is usually a speculative intellectual exercise. When some authors attribute a specific aetiology to an old disease, there is a great risk of committing a methodological error, known as presentism by the modern historiography. The authority of the investigator, more than the weight of the scientific truth, is usually the reason why the diagnosis has remained over the years. The great epidemic of the years 164-165AD and afterwards, could have been smallpox (haemorrhagic form). Claude Galen, the famous doctor, described the symptoms in several books of his great Opera Omnia. For this reason, it is currently known among the scholars as Galen's plague. The epidemic was described for the first time in Seleucia (Mesopotamia). Until now, the actual geographic origin is unknown. We propose here that the beginning might be the kingdom of the old Han dynasty (now the Chinese Popular Republic). The epidemic swept the Roman Empire, from the east to the west, and from the southern to the northern borders. An immediate consequence of the infection was a high morbidity and mortality. In this sense, Galen's epidemic was one of the many factors that caused the fall and destruction of the Roman Empire. On the other hand, there is a general agreement among historians, biographers and researchers that the philosopher emperor Marcus Aurelius Antoninus (121-180AD was affected by the infection in the epidemic wave of 164-165AD. The death of Marcus Aurelius occurred on March 17 in the year 180AD, in Vindobonne, or perhaps Sirminium (near to Vienna). Many authors propose that the cause of the emperor's death was the same epidemic. We consider that it is not possible to demonstrate any of those speculative diagnoses. Finally, the epidemic of 189-190AD, that we have named of Commodus, was probably a different disease to the Galen's plague. There were several kinds of animals affected (anthropozoonoses). In this sense, this infection

  12. The Vague Plague -The continual innovation and spread of BPR and IT in Enterprise Networks

    DEFF Research Database (Denmark)

    Koch, Christian

    1998-01-01

    The empirical point of departure of this article is the erosion of enterprise boundaries, which create new conditions for enterprise actors, i.e. they are to an increasing extent forced to operate in networks. They are confronted with a number of unstable and developing change drivers. The focus ...... as a "plague" like SAP R/3, are actually reshaped by the enterprises....

  13. An Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

    National Research Council Canada - National Science Library

    Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

    2008-01-01

    ... incompatible vaccine mixtures. Intradermally administered arrays of vaccines for protection from anthrax, botulism, plague, and staphylococcal toxic shock were biocompatible in vivo, retained potent antibody responses...

  14. Serological and PCR investigation of Yersinia pestis in potential reservoir hosts from a plague outbreak focus in Zambia.

    Science.gov (United States)

    Nyirenda, S S; Hang'ombe, B M; Mulenga, E; Kilonzo, B S

    2017-07-28

    Plague is a bacterial zoonotic disease, caused by Yersinia pestis. Rodents are the natural hosts with fleas as the vehicle of disease transmission. Domestic and wild dogs and cats have also been identified as possible disease hosts. In Zambia, plague outbreaks have been reported in the Southern and Eastern regions in the last 20 years. Based on these observations, Y. pestis could possibly be endemically present in the area. To substantiate such possibility, sera samples were collected from rodents, shrews, dogs and cats for detection of antibodies against Fraction 1 gene (Fra1) of Y. pestis while organs from rodents and shrews, and fleas from both dogs and rodents were collected to investigate plasminogen activator gene (pla gene) of Y. pestis using ELISA and PCR respectively. A total of 369 blood samples were collected from domestic carnivores, shrews and domestic and peri-domestic rodents while 199 organs were collected from the rodents and shrews. Blood samples were tested for antibodies against Fra1 antigen using ELISA and 3% (5/165) (95% CI 0.99-6.93%) dogs were positive while all cats were negative. Of 199 sera from rodents and shrews, 12.6% (95% CI 8.30-17.98%) were positive for antibodies against Fra1 using anti-rat IgG secondary antibody while using anti-mouse IgG secondary antibody, 17.6% (95% CI 12.57-23.60%) were positive. PCR was run on the organs and 2.5% (95% CI 0.82-5.77%) were positive for plasminogen activator gene of Y. pestis and the amplicons were sequenced and showed 99% identity with Y. pestis reference sequences. All 82 fleas collected from animals subjected to PCR, were negative for pla gene. The specific rat-flea and dog-flea indices were 0.19 and 0.27 respectively, which were lower than the level required to enhance chances of the disease outbreak. We concluded that plague was still endemic in the area and the disease may infect human beings if contact is enhanced between reservoir hosts and flea vectors. The lower specific rodent

  15. O Carnaval, a peste e a 'espanhola' Carnival, the plague, and the Spanish flu

    Directory of Open Access Journals (Sweden)

    Ricardo Augusto dos Santos

    2006-03-01

    Full Text Available Este texto apresenta algumas imagens (fotografias, pinturas relativas às epidemias de Peste e Gripe Espanhola. Procuramos demonstrar como fenômenos históricos analisados comparativamente revelam semelhanças em distintas formações sociais. Apesar das diferenças de tempo e espaço, existem manifestações simbólicas coletivas invariáveis nas epidemias. Por exemplo, em várias ocorrências de peste, gripe ou cólera, a associação entre doença e castigo divino está presente. De forma análoga, indivíduos de comportamento "suspeito" foram e são apontados como propagadores das enfermidades, sejam pobres, judeus, irlandeses ou negros.The article presents photographic and painted images related to epidemics of the plague and Spanish flu. Comparative analyses of this type of historical phenomena reveal similarities between diverse social formations. Despite differences in time and space, epidemics display certain invariable symbolic collective expressions. For example, disease and divine punishment have been linked during a number of plague, flu, or cholera epidemics. Similarly, individuals whose behavior is 'suspicious' have been accused of spreading illness - for instance, the poor, Jews, Irish, or blacks.

  16. Molecular, serological and epidemiological observations after a suspected outbreak of plague in Nyimba, eastern Zambia.

    Science.gov (United States)

    Nyirenda, Stanley S; Hang'ombe, Bernard M; Kilonzo, Bukheti S; Kabeta, Mathews N; Cornellius, Mundia; Sinkala, Yona

    2017-01-01

    Plague is a re-emerging zoonotic disease caused by the bacterium Yersinia pestis. The disease has caused periodic global devastation since the first outbreak in the 6th century. Two months after a suspected plague outbreak in Nyimba district, samples were collected from 94 livestock (goats and pigs), 25 rodents, 6 shrews and 33 fleas. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) techniques were used to investigate the presence of Y. pestis, which showed that 16.0% (4/25) of rodents, 16.7% (1/6) of shrews (Crocidura spp) and 6.0% (5/83) of goats were positive for IgG antibodies against Fraction 1 antigen of Y. pestis. Plasminogen activator (Pla) gene (DNA) of Y. pestis was detected in five pools containing 36.4% (12/33) fleas collected from pigs (n = 4), goats (n = 5) and rodents (n = 3). The detection of Pla gene in fleas and IgG antibodies against Fraction1 antigen in rodents, shrews and goats suggest that Y. pestis had been present in the study area in the recent past. © The Author(s) 2016.

  17. Epidemics in the news: Health and hygiene in the press in periods of crisis.

    Science.gov (United States)

    de Almeida, Maria Antónia Pires

    2013-10-01

    How did scientific knowledge reach the public? Using the press and keeping in mind the population's limited access to written material, this paper establishes how the latest scientific news was divulged to unspecialised audiences. In times of sanitary crisis in Oporto, such as the cholera morbus epidemic of 1854-1856, the bubonic plague in 1899 and the 1918 influenza pandemic, newspapers were important sources to access the information and advice given to the public. A database of 6700 articles, medical reports and advertisements published in daily newspapers reveals the state of the art of medical science. It also reveals the importance given by health authorities and journalists to the publication of recent discoveries and adequate hygiene procedures to prevent the spread of the epidemics. This is a subject that contributes to the debates on the dissemination of science and on the place that Portugal occupied in the international scientific community.

  18. The Entangled History of Sadoka (Rinderpest) and Veterinary Science in Tanzania and the Wider World, 1891-1901.

    Science.gov (United States)

    Sunseri, Thaddeus

    2015-01-01

    Scholarship on the Tanzanian Rinderpest epizootic of the 1890s has assumed that German colonizers understood from the start that they were confronting the same disease that had afflicted Eurasia for centuries. Outward indicators of the epizootic, known locally as sadoka, especially wildlife destruction, were unknown in Europe, leading German veterinarians to doubt that the African disease was Rinderpest. Financial constraints and conflicting development agendas, especially tension between ranching and pastoralism, deterred early colonial applications of veterinary science that might have led to an early diagnosis. European veterinarians, guarding their authority against medical researchers, opposed inoculation therapies in the case of Rinderpest in favor of veterinary policing despite recent breakthroughs in vaccine research. The virus was not identified before reaching South Africa in 1896, but this breakthrough had little influence on policy in East Africa. Yet emergent international disease conventions directed at bubonic plague entangled with veterinary policy in East Africa.

  19. 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

  20. Leprosy in a Lombard-Avar cemetery in central Italy (Campochiaro, Molise, 6th-8th century AD): ancient DNA evidence and demography.

    Science.gov (United States)

    Rubini, Mauro; Zaio, Paola; Spigelman, Mark; Donoghue, Helen D

    2017-09-01

    The study of past infectious diseases increases knowledge of the presence, impact and spread of pathogens within ancient populations. Polymerase chain reaction (PCR) was used to examine bones for the presence of Mycobacterium leprae ancient DNA (aDNA) as, even when leprosy is present, bony changes are not always pathognomonic of the disease. This study also examined the demographic profile of this population and compared it with two other populations to investigate any changes in mortality trends between different infectious diseases and between the pre-antibiotic and antibiotic eras. The individuals were from a site in Central Italy (6th-8th CE) and were examined for the presence of Mycobacterium leprae aDNA. In addition, an abridged life mortality table was constructed. Two individuals had typical leprosy palaeopathology, and one was positive for Mycobacterium leprae aDNA. However, the demographic profile shows a mortality curve similar to that of the standard, in contrast to a population that had been subjected to bubonic plague. This study shows that, in the historical population with leprosy, the risk factors for health seem to be constant and distributed across all age classes, similar to what is found today in the antibiotic era. There were no peaks of mortality equivalent to those found in fatal diseases such as the plague, probably due to the long clinical course of leprosy.

  1. Q&A: A Conversation With David France - The HIV/AID Plague Years and Where We Stand Now.

    Science.gov (United States)

    Wehrwein, Peter

    2017-02-01

    Journalist David France's How to Survive A Plague is a searing firsthand account of the early years of the HIV/AIDS epidemic in New York City. AIDS activists, most of them gay men, were fighting for their lives. Researchers, politicians, public health officials, and pharma were slow to respond-or resisted outright.

  2. Detecting plague-host abundance from space: Using a spectral vegetation index to identify occupancy of great gerbil burrows

    NARCIS (Netherlands)

    Wilschut, Liesbeth I.; Heesterbeek, Johan A.P.; Begon, Mike; de Jong, Steven M.; Ageyev, Vladimir; Laudisoit, Anne; Addink, Elisabeth A.

    2018-01-01

    In Kazakhstan, plague outbreaks occur when its main host, the great gerbil, exceeds an abundance threshold. These live in family groups in burrows, which can be mapped using remote sensing. Occupancy (percentage of burrows occupied) is a good proxy for abundance and hence the possibility of an

  3. New alternatives in the control of plagues and projections of the ICA in the handling of the residuals in agricultural products

    International Nuclear Information System (INIS)

    Clavijo Navarro, P.E.

    1995-01-01

    The strategies are described indicated by the ICA for the control of plagues and of toxic residuals of agro-chemicals in the agricultural products, with emphasis in the implementation of mechanisms like the integrated control of plagues. It stands out the paper of the bio-insecticides as alternative to the agro-chemicals use and enter these stable products they are mentioned with the help of Bacillus thuringiensis, Beauveria bassiana, Nomuraea rileyi, Metarhizium anisoplidae and Verticilium lecanni. Some implications of the presence of toxic residuals are mentioned in Colombian export fruits and the measures that have been adopted to avoid them, as well as some mechanisms adopted in the international environment with the same end. The effective legislation is indicated as for prohibition and restriction of plaguicides use

  4. Exploring the Outside and the Inside: Double Vision in Joan Slonczewski’s Brain Plague

    OpenAIRE

    Mateusz Marecki

    2012-01-01

    With its vision of how the possibility of enhancing the human brain by means of intelligent microbes would change the nature of humanity, Slonczewski‘s Brain Plague (2000) provides a fertile ground for multiple interpretations. Deploying the theme of intelligence and the brain, it belongs to the literature linked to the life sciences. In terms of its generic aspect, the novel should be classified as hards cience fiction, because it is predicated on scientific underpinnings. In this paper, how...

  5. Tendência secular da peste no Estado do Ceará, Brasil Secular plague trend in Ceará State, Brazil

    Directory of Open Access Journals (Sweden)

    Antonia Ivoneida Aragão

    2007-03-01

    Full Text Available Após a sua introdução no Ceará, Brasil, em 1900, a peste focalizou-se em sete complexos ecológicos: Chapada do Araripe e Serras da Ibiapaba, do Baturité, do Machado, das Matas, da Pedra Branca e de Uruburetama. As atividades de vigilância nesses focos no período de 1935/2004 foram desenvolvidas sucessivamente pelo Departamento Nacional de Saúde, Serviço Nacional de Peste, Departamento Nacional de Endemias Rurais, Superintendência de Campanhas de Saúde Pública, Fundação Nacional de Saúde e finalmente pela Secretaria de Vigilância em Saúde. A análise dos dados levantados sobre a ocorrência de casos humanos nesses 70 anos permite identificar diferentes padrões de circulação da enfermidade na população humana, caracterizados pela alternância de momentos de elevadas incidências e de silêncio, possibilitando estabelecer uma periodização cronológica com características epidemiológicas próprias. Conclui-se desses resultados que a peste ainda deve ser considerada uma ameaça potencial, o que justifica revitalizar as ações de vigilância epidemiológica, o que só ocorrerá com o fortalecimento de todas as instâncias do Sistema Único de Saúde.After its introduction into the State of Ceará, Brazil, in 1900, the plague was established in seven ecological complexes: Chapada do Araripe and the Ibiapaba, Baturité, Machado, Matas, Pedra Branca, and Uruburetama mountains. These natural foci were monitored successively from 1935 to 2004 by the National Health Department, National Plague Service, National Department of Rural Endemics, Superintendency of Public Health Campaigns, National Health Foundation, and finally by the National Health Surveillance Secretariat. Data analysis on human cases during these 70 years allowing identifying different plague circulation patterns in the human population, alternating high incidence with silent periods and characterizing a chronological periodicity with unique epidemiological

  6. Temporal variation in the prevalence of the crayfish plague pathogen, Aphanomyces astaci, in three Czech spiny-cheek crayfish populations

    Czech Academy of Sciences Publication Activity Database

    Matasová, K.; Kozubíková, E.; Svoboda, J.; Jarošík, Vojtěch; Petrusek, A.

    -, č. 401 (2011), s. 1-9 ISSN 1961-9502 R&D Projects: GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60050516 Keywords : crayfish plague * molecular methosd * dominance Subject RIV: EH - Ecology, Behaviour Impact factor: 1.520, year: 2011

  7. Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.

    Science.gov (United States)

    Yang, Huiying; Wang, Tong; Tian, Guang; Zhang, Qingwen; Wu, Xiaohong; Xin, Youqian; Yan, Yanfeng; Tan, Yafang; Cao, Shiyang; Liu, Wanbing; Cui, Yujun; Yang, Ruifu; Du, Zongmin

    2017-01-01

    Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague

    Science.gov (United States)

    Koshel, E. I.; Aleshin, V. V.; Eroshenko, G. A.; Kutyrev, V. V.

    2014-01-01

    Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmit Yersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus, Microtus socialis, and Allactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema, Psyllotylenchus, and Spilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina. PMID:24804197

  9. A polymerase chain reaction assay for detection of virulent and attenuated strains of duck plague virus.

    Science.gov (United States)

    Xie, Liji; Xie, Zhixun; Huang, Li; Wang, Sheng; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Luo, Sisi

    2017-11-01

    Sequence analysis of duck plague virus (DPV) revealed that there was a 528bp (B fragment) deletion within the UL2 gene of DPV attenuated vaccine strain in comparison with field virulent strains. The finding of gene deletion provides a potential differentiation test between DPV virulent strain and attenuated strain based on their UL2 gene sizes. Thus we developed a polymerase chain reaction (PCR) assay targeting to the DPV UL2 gene for simultaneous detection of DPV virulent strain and attenuated strain, 827bp for virulent strain and 299bp for attenuated strain. This newly developed PCR for DPV was highly sensitive and specific. It detected as low as 100fg of DNA on both DPV virulent and attenuated strains, no same size bands were amplified from other duck viruses including duck paramyxovirus, duck tembusu virus, duck circovirus, Muscovy duck parvovirus, duck hepatitis virus type I, avian influenza virus and gosling plague virus. Therefore, this PCR assay can be used for the rapid, sensitive and specific detection of DPV virulent and attenuated strains affecting ducks. Copyright © 2017. Published by Elsevier B.V.

  10. [Remain true to our original aspiration for farewell to the God of Plague, compose the new chapter for the national schistosomiasis control programme scientifically-Commemoration of 60th anniversary of publishing Chairman Mao Zedong's two poems "Farewell to the God of Plague"].

    Science.gov (United States)

    Xiao-Nong, Zhou; Shi-Zhu, Li; Qing-Biao, Hong; Kun, Yang; Shan, Lü; Jing, Xu

    2018-02-26

    This paper reviews the huge promotion of Chairman Mao Zedong's two poems entitled "Farewell to the God of Plague" which were published 60 years ago, and the great achievements of the national schistosomiasis control programme in China. The publication of the two poems promotes the establishment of the mechanism for the national schistosomiasis control programme in China, and in addition, the schistosomiasis control spirit of the people from Yujiang County is still the source of power for the promotion of transferring the schistosomiasis control to elimination stage in China. Now, that we commemorate the 60th anniversary of publishing Chairman Mao Zedong's two poems entitled "Farewell to the God of Plague" means we remain the true to our original aspiration to serve the people forever, which is also to promote the progress of schistosomiasis elimination in China according to the law, the scientific principle, and local conditions, so as to contribute our efforts for realizing the healthy China's dream.

  11. Misidentification of Yersinia pestis by automated systems, resulting in delayed diagnoses of human plague infections--Oregon and New Mexico, 2010-2011.

    Science.gov (United States)

    Tourdjman, Mathieu; Ibraheem, Mam; Brett, Meghan; Debess, Emilio; Progulske, Barbara; Ettestad, Paul; McGivern, Teresa; Petersen, Jeannine; Mead, Paul

    2012-10-01

    One human plague case was reported in Oregon in September 2010 and another in New Mexico in May 2011. Misidentification of Yersinia pestis by automated identification systems contributed to delayed diagnoses for both cases.

  12. Angels with Nanotech Wings: Magic, Medicine and Technology in Aronofksky's The Fountain, Gibson's The Neuromancer and Slonczewski's Brain Plague

    NARCIS (Netherlands)

    Lord, C.M.

    2009-01-01

    Darren Aronofsky's feature film The Fountain (2006), William Gibson's celebrated novel The Neuromancer (1984)and Joan Slonczewski'ls best-seller Brain Plague (2000), all have in common a preoccupation with the neuroscientific secrets of the brain. But more than this, all these works that explore the

  13. [Genodiagnosis and molecular typing of the pathogens for plague, cholera, and anthrax].

    Science.gov (United States)

    Kutyrev, V V; Smirnova, N I

    2003-01-01

    The paper contains a survey of published data about the use of DNA-diagnostics in indicating and identifying the causative agents of highly dangerous infections like plague, cholera and anthrax. A discussion of data about the genetic relationship between strains of the mentioned causative agents isolated from different sources by using the molecular-typing methods as well as about the evolution ties between strains of different origins is in the focus of attention. Results of comparative studies of nucleotide sequences of genomes or of individual genomes in different Yersinia pestis, Vibrio cholerae and Bacillus anthracis strains, which are indicative of the evolution of their pathogenicity, are also under discussion.

  14. [Macro- and microevolution as related to the problem of origin and global expansion of the plague pathogen Yersinia pestis].

    Science.gov (United States)

    Suntsov, V V; Suntsova, N I

    2008-01-01

    The ratio of macro- and microevolutionary processes is considered with reference to the ecological scenario of the origin of the plague pathogen and its subsequent natural and anthropogenic global expansion. The macroevolutionary transformation of the ancestral pseudotuberculosis microbe clone into the initial plague microbe Yersinia pestis tarbagani occurred in Central Asia at the end of the Late Pleistocene by a "vertical" Darwinian way in an inadaptive heterothermal continual intermediate environment--the Mongolian marmot Marmota sibirica-flea Oropsylla silantiewi system--via a sequence of unstable and currently extinct intermediate forms. Its natural geographic expansion on the "oil spot" principle in the postglacial time led to the microevolutionary formation of 20-30 hostal subspecies circulating in populations of the background species of burrowing rodents and pikas in arid areas of Eurasia. The intercontinental spread of the "marmot" and "rat" pathogen subspecies in the past few centuries has been exclusively anthropogenic, with the involvement of synanthropic (ship) rats.

  15. Fleas and flea control

    Directory of Open Access Journals (Sweden)

    Dautović Živomir

    2002-01-01

    Full Text Available Fleas as hemeatophagous arthropodes take part in the spreading of certain diseases such as bubonic plague, murine typhus, tick-borne typhus tularaemia, or can be transitory hosts for certain species of cestodes for dogs and cats. Depending on the type of host on which fleas persist and the habitat, measures that can be taken to control them can be only sanitary-hygiene, individual, or treatment of the habitat. Sanitary-hygiene measures mostly consist of regular cleaning. Individual protection implies the use of insecticides for re-impregnating clothing, spraying clothing and the use of repellents. Treatment of habitats comprises the use of insecticides of the group of organophosphates, metyl-carbamates, pyrethroids and organo-chlorine compounds, instruments for dusting and spraying. In addition to these compounds, preparations based on imidaclopride, fipronyl and inhibitors of insect growth (IGRs and development (IDIs are also used. Flea control in household pets is implemented using measures of individual protection and treatment of their habitats.

  16. Rapid and sensitive detection of Yersinia pestis using amplification of plague diagnostic bacteriophages monitored by real-time PCR.

    Directory of Open Access Journals (Sweden)

    Kirill V Sergueev

    Full Text Available BACKGROUND: Yersinia pestis, the agent of plague, has caused many millions of human deaths and still poses a serious threat to global public health. Timely and reliable detection of such a dangerous pathogen is of critical importance. Lysis by specific bacteriophages remains an essential method of Y. pestis detection and plague diagnostics. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this work was to develop an alternative to conventional phage lysis tests--a rapid and highly sensitive method of indirect detection of live Y. pestis cells based on quantitative real-time PCR (qPCR monitoring of amplification of reporter Y. pestis-specific bacteriophages. Plague diagnostic phages phiA1122 and L-413C were shown to be highly effective diagnostic tools for the detection and identification of Y. pestis by using qPCR with primers specific for phage DNA. The template DNA extraction step that usually precedes qPCR was omitted. phiA1122-specific qPCR enabled the detection of an initial bacterial concentration of 10(3 CFU/ml (equivalent to as few as one Y. pestis cell per 1-microl sample in four hours. L-413C-mediated detection of Y. pestis was less sensitive (up to 100 bacteria per sample but more specific, and thus we propose parallel qPCR for the two phages as a rapid and reliable method of Y. pestis identification. Importantly, phiA1122 propagated in simulated clinical blood specimens containing EDTA and its titer rise was detected by both a standard plating test and qPCR. CONCLUSIONS/SIGNIFICANCE: Thus, we developed a novel assay for detection and identification of Y. pestis using amplification of specific phages monitored by qPCR. The method is simple, rapid, highly sensitive, and specific and allows the detection of only live bacteria.

  17. Duck plague: carrier state and gross pathology in black ducks

    Science.gov (United States)

    Ossa, Jorge E.

    1975-01-01

    Duck plague (UP) is a highly fatal disease of ducks, geese, and swans (family Anatidae), produced by a reticulo-endotheliotrophic virus classified as a member of the Herpesvirus group. The disease was recognized in Europe in 1949. On the American continent, the disease was first diagnosed in the United States in 1967. Very little is known of DP virus ecology, particularly of the mechanisms of interepizootic survival and movement. The tendency of the IIerpesviruses to enter into a quiescent state after an overt or inapparent infection is a proven characteristic for most of the members of this group. Herpes simplex, which is the model of the Herpesviruses, is said to be the classical example of a persistent recurrent viral infection. Burnet and Williams (4) were the first to recognize this kind of relationship between herpes simplex and its host in 1939. Later, it was found that the reactivation of the virus can be brought on by a variety of stimuli either physiological (menstruation), pathological (anaphylactic shock), chemical (pesticides) or physical (sunburn). This same latency property has been proved for every member of this group of viruses which has been studied adequately, DP is among the few Herpesviruses for which the carrier state has not been demonstrated, but there is circumstantial evidence suggesting it. The carrier state for DP seems to be a likely explanation for the persistence and the particular pattern of movement of this disease.

  18. Nursing Care Given to the Plague Infected Patients in the Hospital General of Madrid (Spain in the 17th Century.

    Directory of Open Access Journals (Sweden)

    Manuel Jesús García Martínez

    2016-12-01

    Full Text Available This study reveals the work developed by the nurses of the Hospital general of Madrid (Spain in the treatment of the plague, and the training they received for their welfare tasks in the 17th century. Since the end of the 16th century, nurses knew and implemented a set of techniques and medicines to alleviate the terrible disease of the plague and, despite the scarce knowledge about the disease existing at the time, they sought to prevent the contagion with hygienic and dietary measures, and physical isolation. This study shows through which actions and in which conditions nurses worked to deal with such a terrible disease. All this helps to get a full knowledge of the development of the work done by nurses in the last five centuries and, therefore, to determine the evolution and shaping of the nursing profession in our country.

  19. Temperature-sensitive mutants of fowl plague virus: isolation and genetic characterization

    International Nuclear Information System (INIS)

    Almond, J.W.; McGeoch, D.; Barry, R.D.

    1979-01-01

    Forty-nine temperature-sensitive mutants of fowl plague virus (FPV) strain Rostock and four ts mutants of FPV-strain Dobson were isolated by utilizing two methods of plaque screening, after either spontaneous or chemically induced mutagenesis. Twenty-nine of the FPV-Rostock mutants were further characterized by genetic recombination studies and were found to fall into six high frequency recombination groups. The genome segment carrying the ts mutation in each group was identified by analyzing the gene composition of ts + recombinants generated from crosses between representatives of each group and ts mutants of FPV-Dobson. It was concluded that the six groups correspond to mutations in six different genome segments, namely, those coding for the P 1 , P 2 , P 3 , HA, NP, and NS proteins

  20. Dermal neutrophil, macrophage and dendritic cell responses to Yersinia pestis transmitted by fleas.

    Directory of Open Access Journals (Sweden)

    Jeffrey G Shannon

    2015-03-01

    Full Text Available Yersinia pestis, the causative agent of plague, is typically transmitted by the bite of an infected flea. Many aspects of mammalian innate immune response early after Y. pestis infection remain poorly understood. A previous study by our lab showed that neutrophils are the most prominent cell type recruited to the injection site after intradermal needle inoculation of Y. pestis, suggesting that neutrophil interactions with Y. pestis may be important in bubonic plague pathogenesis. In the present study, we developed new tools allowing for intravital microscopy of Y. pestis in the dermis of an infected mouse after transmission by its natural route of infection, the bite of an infected flea. We found that uninfected flea bites typically induced minimal neutrophil recruitment. The magnitude of neutrophil response to flea-transmitted Y. pestis varied considerably and appeared to correspond to the number of bacteria deposited at the bite site. Macrophages migrated towards flea bite sites and interacted with small numbers of flea-transmitted bacteria. Consistent with a previous study, we observed minimal interaction between Y. pestis and dendritic cells; however, dendritic cells did consistently migrate towards flea bite sites containing Y. pestis. Interestingly, we often recovered viable Y. pestis from the draining lymph node (dLN 1 h after flea feeding, indicating that the migration of bacteria from the dermis to the dLN may be more rapid than previously reported. Overall, the innate cellular host responses to flea-transmitted Y. pestis differed from and were more variable than responses to needle-inoculated bacteria. This work highlights the importance of studying the interactions between fleas, Y. pestis and the mammalian host to gain a better understanding of the early events in plague pathogenesis.

  1. Monitoreo of the feromonas traps in the control of the plague Lasioderma serricorne (F. in the Managerial Unit of Base Alfredo López Brito.

    Directory of Open Access Journals (Sweden)

    Marta Rosa Rodríguez Valero

    2012-12-01

    Full Text Available Due to their inigualable quality, the Cuban tobacco is one of the cultivations that bigger quantity of foreign currencies contributes to the country, but it is attacked by different plagues, in the different stages for those that it passes until its commercialization in leaves or as elaborated product. In the warehouses the most destructive plague is the Lasioderma serricorne (F. and to combat it in the Managerial Unit of Base Alfredo López Brito of Cabaiguán, the fosfamina, toxic product with high price is used in foreign currencies, the same one is applied with a bimonthly frequency, that is to say, every 60 days, for which the present work had as objective to lengthen the date of application of the fosfamina by means of the use of the feromonas traps to achieve a saving to the Unit and to improve the environmental conditions in the same one. The obtained results allowed to diminish the quantity of necessary fosfamina significantly to control the plague, the Unit saved during 4 months in those that it was carried out this work. $869.40 in national currency and $343.55 in CUC a positive impact also took place about the health of the workers and the one intones.

  2. Manipulation of Interleukin-1β and Interleukin-18 Production by Yersinia pestis Effectors YopJ and YopM and Redundant Impact on Virulence*

    Science.gov (United States)

    Ratner, Dmitry; Orning, M. Pontus A.; Starheim, Kristian K.; Marty-Roix, Robyn; Proulx, Megan K.; Goguen, Jon D.; Lien, Egil

    2016-01-01

    Innate immunity plays a central role in resolving infections by pathogens. Host survival during plague, caused by the Gram-negative bacterium Yersinia pestis, is favored by a robust early innate immune response initiated by IL-1β and IL-18. These cytokines are produced by a two-step mechanism involving NF-κB-mediated pro-cytokine production and inflammasome-driven maturation into bioactive inflammatory mediators. Because of the anti-microbial effects induced by IL-1β/IL-18, it may be desirable for pathogens to manipulate their production. Y. pestis type III secretion system effectors YopJ and YopM can interfere with different parts of this process. Both effectors have been reported to influence inflammasome caspase-1 activity; YopJ promotes caspase-8-dependent cell death and caspase-1 cleavage, whereas YopM inhibits caspase-1 activity via an incompletely understood mechanism. However, neither effector appears essential for full virulence in vivo. Here we report that the sum of influences by YopJ and YopM on IL-1β/IL-18 release is suppressive. In the absence of YopM, YopJ minimally affects caspase-1 cleavage but suppresses IL-1β, IL-18, and other cytokines and chemokines. Importantly, we find that Y. pestis containing combined deletions of YopJ and YopM induces elevated levels of IL-1β/IL-18 in vitro and in vivo and is significantly attenuated in a mouse model of bubonic plague. The reduced virulence of the YopJ-YopM mutant is dependent on the presence of IL-1β, IL-18, and caspase-1. Thus, we conclude that Y. pestis YopJ and YopM can both exert a tight control of host IL-1β/IL-18 production to benefit the bacteria, resulting in a redundant impact on virulence. PMID:26884330

  3. Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

    2017-07-01

    Full Text Available The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

  4. Assessment of a recombinant F1-V fusion protein vaccine intended to protect Canada lynx (Lynx canadensis) from plague

    Science.gov (United States)

    Wolfe, Lisa L.; Shenk, Tanya M.; Powell, Bradford; Rocke, Tonie E.

    2011-01-01

    As part of an ongoing restoration program in Colorado, USA, we evaluated adverse reactions and seroconversion in captive Canada lynx (Lynx canadensis) after vaccination with a recombinant F1-V fusion protein vaccine against Yersinia pestis, the bacterium that causes plague. Ten adult female lynx received the F1-V vaccine; 10 source- and age-matched lynx remained unvaccinated as controls. All of the vaccinated and control lynx remained apparently healthy throughout the confinement period. We observed no evidence of injection site or systemic reactions to the F1-V vaccine. Among vaccinated lynx, differences in log10 reciprocal antibody titers measured in sera collected before and after vaccination (two doses) ranged from 1.2 to 5.2 for anti-F1 antibodies and from 0.6 to 5.2 for anti-V antibodies; titers in unvaccinated lynx did not change appreciably over the course of confinement prior to release, and thus differences in anti-F1 (P=0.003) and anti-V (P=0.0005) titers were greater among vaccinated lynx than among controls. Although our findings suggest that the F1-V fusion protein vaccine evaluated here is likely to stimulate antibody responses that may help protect Canada lynx from plague, we observed no apparent differences in survival between vaccinated and unvaccinated subject animals. Retrospectively, 22 of 50 (44%; 95% confidence interval 29–59%) unvaccinated lynx captured or recaptured in Colorado during 2000–08 had passive hemagglutination antibody titers >1:16, consistent with exposure to Y. pestis; paired pre- and postrelease titers available for eight of these animals showed titer increases similar in magnitude to those seen in response to vaccination, suggesting at least some lynx may naturally acquire immunity to plague in Colorado habitats.

  5. Hijacking of the pleiotropic cytokine interferon-γ by the type III secretion system of Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Claire Gendrin

    Full Text Available Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague.

  6. Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

    Science.gov (United States)

    Sun, Wei; Sanapala, Shilpa; Rahav, Hannah; Curtiss, Roy

    2015-11-27

    A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effect of temperature and relative humidity on the development times and survival of Synopsyllus fonquerniei and Xenopsylla cheopis, the flea vectors of plague in Madagascar.

    Science.gov (United States)

    Kreppel, Katharina S; Telfer, Sandra; Rajerison, Minoarisoa; Morse, Andy; Baylis, Matthew

    2016-02-11

    Plague, a zoonosis caused by Yersinia pestis, is found in Asia, the Americas but mainly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. In the highlands of Madagascar, plague is transmitted predominantly by two flea species which coexist on the island, but differ in their distribution. The endemic flea, Synopsyllus fonquerniei, dominates flea communities on rats caught outdoors, while the cosmopolitan flea, Xenopsylla cheopis, is found mostly on rats caught in houses. Additionally S. fonquerniei seems restricted to areas above 800 m. Climatic constraints on the development of the two main vectors of plague could explain the differences in their distribution and the seasonal changes in their abundance. Here we present the first study on effects of temperature and relative humidity on the immature stages of both vector species. We examined the two species' temperature and humidity requirements under experimental conditions at five different temperatures and two relative humidities. By employing multivariate and survival analysis we established the impact of temperature and relative humidity on development times and survival for both species. Using degree-day analysis we then predicted the average developmental threshold for larvae to reach pupation and for pupae to complete development under each treatment. This analysis was undertaken separately for the two relative humidities and for the two species. Development times and time to death differed significantly, with the endemic S. fonquerniei taking on average 1.79 times longer to complete development and having a shorter time to death than X. cheopis under adverse conditions with high temperature and low humidity. Temperature had a significant effect on the development times of flea larvae and pupae. While humidity did not affect the development times of either species, it did influence the time of death of S. fonquerniei. Using degree-day analysis we estimated an

  8. INVESTIGATING A MURDER THE CASE OF THE JUSTINIANIC PLAGUE IN SCYTHIA MINOR

    Directory of Open Access Journals (Sweden)

    Dragos Mitrofan

    2015-03-01

    Full Text Available The study beforehand applies a logical scheme of analysis over a possible presence of the Justinianic plague in the province of Scythia Minor. Following a logic borrowed from the criminalistics, we tried to apply this scheme in order to see if the theory of presence of the epidemic is viable in the given region. Although we have not come with decisive pieces of evidence, a great deal of research is still necessary in order to confirm or infirm this theory. We therefore aim to open a discussion, considering the problem plausible, for the disease had the means and opportunity to affect the province. As previously stated this study is merely a plan of study that shall be developed in a forthcoming work.

  9. An ontological framework for model-based problem-solving

    NARCIS (Netherlands)

    Scholten, H.; Beulens, A.J.M.

    2012-01-01

    Multidisciplinary projects to solve real world problems of increasing complexity are more and more plagued by obstacles such as miscommunication between modellers with different disciplinary backgrounds and bad modelling practices. To tackle these difficulties, a body of knowledge on problems, on

  10. Histopatologia da infecção por Yersinia pestis em roedores de focos de peste do Nordeste brasileiro Histopathology of Yersinia pestis infection in rodents from plague foci of Brazilian Northeast

    Directory of Open Access Journals (Sweden)

    Eridan M. Coutinho

    1982-06-01

    Full Text Available O presente trabalho mostra a histopatologia da infecção pela Yersinia pestis, entre as diferentes espécies de roedores silvestres e comensais (cricetídeos, equimídeos, murídeos e cavídeos que ocorrem na zona endêmica de peste do Nordeste do Brasil. Estes roedores foram encontrados naturalmente infectados nos campos ou inoculados experimentalmente no laboratório (vias percutânea, subcutânea ou picada de pulgas com cepas locais e/ou estrangeiras de Yersiniapestis. Quase todos os animais, exceto alguns dos cavídeos, desenvolveram a forma bubosepticêmica da peste. Entre as lesões encontradas, a necrose coagulativa multifocal do fígado, a pneumonite intersticial aguda difusa e a atrofia linfoide do baço, podem, por sua constância, ser consideradas como os principais indicadores histológicos da infecção pestosa, embora estas lesões não sejam exclusivas da peste. A diversidade e a intensidade das lesões entre os Zygodontomys lasiurus pixuna, podem explicar a mortalidade elevada desta espécie e a disseminação da peste nos focos naturais do Nordeste brasileiro. Cricetídeos e murídeos mostraram alterações histopatológicas qualitativamente semelhantes. A resistência dos cavídeos à infecção pestosa foi evidenciada pela sobrevida desses roedores à fase aguda da infecção e pelo desenvolvimento de uma reação histiocitária interna, delimitando as áreas abscedadas. è possível que estas lesões crônicas abriguem bacilos virulentos, que permitirão a reinfecção periódica das pulgas e conseqüente reativação do processo epizoótico.In this paper, the histopathological aspects of plague infection in different species of wild and domestic rodents (cricetidae, echymidae, muridae and cavidae are described. All of them had been trapped in endemic plague areas and harboured natural infection, while others were laboratory infected by different routes (percutaneous, subcutaneous rout, fleas bite. Several national and

  11. Comparing bacterial community composition between healthy and white plague-like disease states in Orbicella annularis using PhyloChip™ G3 microarrays

    Science.gov (United States)

    Kellogg, Christina A.; Piceno, Yvette M.; Tom, Lauren M.; DeSantis, Todd Z.; Gray, Michael A.; Zawada, David G.; Andersen, Gary L.

    2013-01-01

    Coral disease is a global problem. Diseases are typically named or described based on macroscopic changes, but broad signs of coral distress such as tissue loss or discoloration are unlikely to be specific to a particular pathogen. For example, there appear to be multiple diseases that manifest the rapid tissue loss that characterizes ‘white plague.’ PhyloChip™ G3 microarrays were used to compare the bacterial community composition of both healthy and white plague-like diseased corals. Samples of lobed star coral (Orbicella annularis, formerly of the genus Montastraea [1]) were collected from two geographically distinct areas, Dry Tortugas National Park and Virgin Islands National Park, to determine if there were biogeographic differences between the diseases. In fact, all diseased samples clustered together, however there was no consistent link to Aurantimonas coralicida, which has been described as the causative agent of white plague type II. The microarrays revealed a large amount of bacterial heterogeneity within the healthy corals and less diversity in the diseased corals. Gram-positive bacterial groups (Actinobacteria, Firmicutes) comprised a greater proportion of the operational taxonomic units (OTUs) unique to healthy samples. Diseased samples were enriched in OTUs from the families Corynebacteriaceae, Lachnospiraceae, Rhodobacteraceae, and Streptococcaceae. Much previous coral disease work has used clone libraries, which seem to be methodologically biased toward recovery of Gram-negative bacterial sequences and may therefore have missed the importance of Gram-positive groups. The PhyloChip™ data presented here provide a broader characterization of the bacterial community changes that occur within Orbicella annularis during the shift from a healthy to diseased state.

  12. 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.

  13. Stationary configurations of the Standard Model Higgs potential

    DEFF Research Database (Denmark)

    Iacobellis, Giuseppe; Masina, Isabella

    2016-01-01

    the stability of the SM electroweak minimum and ii) the value of the Higgs potential at a rising inflection point. We examine in detail and reappraise the experimental and theoretical uncertainties which plague their determination, finding that i) the stability of the SM is compatible with the present data...... at the 1.5σ level and ii) despite the large theoretical error plaguing the value of the Higgs potential at a rising inflection point, the application of such a configuration to models of primordial inflation displays a 3σ tension with the recent bounds on the tensor-to-scalar ratio of cosmological...

  14. Detecting plague-host abundance from space: Using a spectral vegetation index to identify occupancy of great gerbil burrows

    Science.gov (United States)

    Wilschut, Liesbeth I.; Heesterbeek, Johan A. P.; Begon, Mike; de Jong, Steven M.; Ageyev, Vladimir; Laudisoit, Anne; Addink, Elisabeth A.

    2018-02-01

    In Kazakhstan, plague outbreaks occur when its main host, the great gerbil, exceeds an abundance threshold. These live in family groups in burrows, which can be mapped using remote sensing. Occupancy (percentage of burrows occupied) is a good proxy for abundance and hence the possibility of an outbreak. Here we use time series of satellite images to estimate occupancy remotely. In April and September 2013, 872 burrows were identified in the field as either occupied or empty. For satellite images acquired between April and August, 'burrow objects' were identified and matched to the field burrows. The burrow objects were represented by 25 different polygon types, then classified (using a majority vote from 10 Random Forests) as occupied or empty, using Normalized Difference Vegetation Indices (NDVI) calculated for all images. Throughout the season NDVI values were higher for empty than for occupied burrows. Occupancy status of individual burrows that were continuously occupied or empty, was classified with producer's and user's accuracy values of 63 and 64% for the optimum polygon. Occupancy level was predicted very well and differed 2% from the observed occupancy. This establishes firmly the principle that occupancy can be estimated using satellite images with the potential to predict plague outbreaks over extensive areas with much greater ease and accuracy than previously.

  15. Estudo do roedor Akodon arviculoides, Wagner, 1842 (Cricetidae: importância nos focos pestosos no Brasil The rodent Akodon arviculoides, Wagner, 1842 (Cricetidae: importance in plague focus of Brazil

    Directory of Open Access Journals (Sweden)

    Célio Rodrigues de Almeida

    1986-12-01

    Full Text Available Relata-se a ocorrência do roedor Akodon arviculoides (Wagner, 1842 no foco pestoso do Agreste pernambucano, sua capacidade de sobrevivência, reprodução e o desenvolvimento no cativeiro, a susceptibilidade à infecção pela Yersinia pestis e a importãncia desse roedor nos focos pestosos do Brasil.The occurrence of the rodent Akodon arviculoides Wagner, 1842 in the plague focus of the "Agreste" region of the State of Pernambuco and a report on its ability for survival, reproduction and development in captivity, its susceptibility to Yersinia pestis infection and the role of this rodent species in Brazilian plague foci are reported.

  16. Flea abundance, diversity, and plague in Gunnison's prairie dogs (Cynomys gunnisoni) and their burrows in montane grasslands in northern New Mexico

    Science.gov (United States)

    Megan M. Friggens; Robert R. Parmenter; Michael Boyden; Paulette L. Ford; Kenneth Gage; Paul Keim

    2010-01-01

    Plague, a flea-transmitted infectious disease caused by the bacterium Yersinia pestis, is a primary threat to the persistence of prairie dog populations (Cynomys spp.). We conducted a 3-yr survey (2004-2006) of fleas from Gunnison's prairie dogs (Cynomys gunnisoni) and their burrows in montane grasslands in Valles Caldera National Preserve in New Mexico. Our...

  17. Is rheumatoid arthritis a consequence of natural selection for enhanced tuberculosis resistance?

    Science.gov (United States)

    Mobley, James L

    2004-01-01

    Although the bubonic plague or "Black Death" is notorious for the toll it took on the population of Europe in the middle ages, another epidemic, the "White Death" of tuberculosis is responsible for millions of deaths worldwide over the past 300 years. With one in four deaths due to tuberculosis in Western Europe and the United States in the 19th century, this disease undoubtedly acted as a powerful genetic selective force. The epidemiology of modern day rheumatoid arthritis (RA) is strikingly similar to the epidemiology of tuberculosis 100-200 years ago, suggesting the possibility that genetic factors that enhanced survival in tuberculosis epidemics are now influencing susceptibility to RA. Recent advances in the analysis of genetic polymorphisms associated with disease have identified several genes linked to RA susceptibility that encode proteins involved in the immune response to Mycobacterium tuberculosis infection, including TNF-alpha, NRAMP1, PARP-1, HLA-DRB1, and PADI4. These results suggest that rheumatoid arthritis, and possibly other autoimmune diseases, are modern day manifestations of the genetic selective pressure exerted by tuberculosis epidemics of the recent past.

  18. Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

    Science.gov (United States)

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Plague history: Yersin's discovery of the causative bacterium in 1894 enabled, in the subsequent century, scientific progress in understanding the disease and the development of treatments and vaccines.

    Science.gov (United States)

    Butler, T

    2014-03-01

    The causative bacterium of plague was described and cultured by Alexandre Yersin in Hong Kong in 1894, after which transmission of bacteria from rodents by flea bites was discovered by Jean-Paul Simond in 1898. Effective treatment with antiserum was initiated in 1896, but this therapy was supplanted by sulphonamides in the 1930s and by streptomycin starting in 1947. India suffered an estimated 6 million deaths in 1900-1909, and Vietnam, during its war in 1965-1975, accounted for approximately 80% of the world's cases; since then, African countries have dominated, with >90% of the world's cases in the 1990s and early 21st century. Serological diagnosis with fraction 1 antigen to detect anti-plague antibodies was developed in the 1950s. Vaccine development started in 1897 with killed whole bacterial cells, and this was followed by a live attenuated bacterial vaccine, leading to millions of persons receiving injections, but the benefits of these vaccines remain clouded by controversy. Plasmid-mediated virulence was established in 1981, and this was followed by specific DNA methods that have allowed detection of plague genes in skeletal specimens from European graves of the sixth to 17th centuries. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  20. Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase.

    Science.gov (United States)

    Bearden, Scott W; Sexton, Christopher; Pare, Joshua; Fowler, Janet M; Arvidson, Cindy G; Yerman, Lyudmyla; Viola, Ronald E; Brubaker, Robert R

    2009-01-01

    It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents. Cells of Y. pseudotuberculosis are known to express glucose-6-phosphate dehydrogenase (Zwf) and aspartase (AspA); these activities are not detectable in epidemic Y. pestis due to missense mutations (substitution of proline for serine at amino position 155 of Zwf and leucine for valine at position 363 of AspA). In this study, functional Zwf was found in pestoides strains E, F and G but not seven other enzootic isolates; enzymic activity was associated with retention of serine at amino acid position 155. Essentially, full AspA activity occurred in pestoides isolates where valine (pestoides A, B, C and D) or serine (pestoides E, F, G and I) occupied position 363. Reduced activity occurred in strains Angola and A16, which contained phenylalanine at this position. The kcat but not Km of purified AspA from strain Angola was significantly reduced. In this context, aspA of the recently described attenuated enzootic microtus biovar encodes active valine at position 363, further indicating that functional AspA is a biomarker for avirulence of Y. pestis in man.

  1. Early Modern “Citation Index”? Medical Authorities in Academic Treatises on Plague (1480–1725

    Directory of Open Access Journals (Sweden)

    Karel Černý

    2012-01-01

    Full Text Available 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 time development of popularity. The authorities from various groups (Ancient, Medieval, Arabic, Early Modern are linked together, and “generic authorities” are explained and discussed.

  2. Controlling the geographical spread of infectious disease: plague in Italy, 1347-1851.

    Science.gov (United States)

    Cliff, Andrew D; Smallman-Raynor, Matthew R; Stevens, Peta M

    2009-01-01

    After the establishment of the first quarantine station in the Republic of Ragusa (modern-day Dubrovnik) in 1377, the states and principalities of Italy developed a sophisticated system of defensive quarantine in an attempt to protect themselves from the ravages of plague. Using largely unknown and unseen historical maps, this paper reconstructs the extent and operation of the system used. It is shown that a cordon sanitaire existed around the coast of Italy for several centuries, consisting of three elements: (i) an outer defensive ring of armed sailing boats in the Mediterranean and the Adriatic, (ii) a middle coastal ring of forts and observation towers, and (iii) an inner defensive ring of land-based cavalry. The principles established, although not especially successful at the time against a disease of (then) unknown aetiology, are still used today in attempts to control the spread of infections of animal and human populations.

  3. Supersymmetry and the chiral Schwinger model

    International Nuclear Information System (INIS)

    Amorim, R.; Das, A.

    1998-01-01

    We have constructed the N= (1) /(2) supersymmetric general Abelian model with asymmetric chiral couplings. This leads to a N= (1) /(2) supersymmetrization of the Schwinger model. We show that the supersymmetric general model is plagued with problems of infrared divergence. Only the supersymmetric chiral Schwinger model is free from such problems and is dynamically equivalent to the chiral Schwinger model because of the peculiar structure of the N= (1) /(2) multiplets. copyright 1998 The American Physical Society

  4. Synthesis of RNA segment 1-3 during generation of incomplete influenza A (fowl plague) virus

    International Nuclear Information System (INIS)

    Carter, M.J.; Mahy, B.W.J.

    1982-01-01

    Incomplete influenza A virus (fowl plague Dobson strain) was prepared by undiluted passage in primary chick embryo fibroblast cells. Analysis of released virus RNA revealed a deficiency in RNA segments 1-3, characteristic of incomplete virus formation. The virus yield from a high multiplicity infection with standard virus always showed this deficiency, even when analysed as early as 6 hours post-infection, whereas infection at low multiplicity gave rise to virus indistinghuishable in RNA composition from the parent virus. The relative amounts of intracellular, non-polyadenylated, complementary RNA (template RNA) were found to reflect accurately the eventual RNA composition of released virus, and were altered in phase with PFU:HAU ratio, throughout a von Magnus cycle. (Author)

  5. The use of polyvinyl alcohol glutaraldehyde as solid-phase in ELISA for plague

    Directory of Open Access Journals (Sweden)

    Aureci Maria Araujo

    1996-04-01

    Full Text Available Discs of polyvinyl alcohol cross-linked with glutaraldehyde were synthesized under acid catalysis (H2SO4. Then, the antigen F1 purified from Yersinia pestis was covalently linked to this modified polymer. Afterwards, an enzyme-linked immunosorbent assay (ELISA was established for the diagnosis of plague in rabbit and human. The best conditions for the method were achieved by using 1.3 ¼g of F1 prepared in 0.067 M phosphate buffer, pH 7.2, containing 1 M NaCl (PBS; anti-IgG peroxidase conjugate diluted 6,000 times and as a blocking agent 3% w/v skim milk in PBS. The titration of positive rabbit serum according to this procedure detected antibody concentrations up to 1:12,800 times. The present method, the conventional ELISA and passive haemagglutination assay are compared.

  6. Managing prairie dogs by managing plague: a vaccine for the future?

    Science.gov (United States)

    Johnson, Terry B.; Rocke, Tonie E.; Gober, Pete; Van Pelt, Bill E.; Miller, Michael W.; Tripp, Daniel W.; Abbott, Rachel C.; Bergman, David L.

    2014-01-01

    The Black-footed Ferret Recovery Implementation Team Executive Committee is conducting a project to develop,and (hopefully) eventually implement, a plague vaccination program for prairie dogs. The project is a component of the WesternAssociation of Fish and Wildlife Agencies Grasslands Conservation Initiative. An effective, field-worthy vaccine against plaguecould be the biggest breakthrough in recovery efforts for the black-footed ferret since the 1981 rediscovery of wild ferrets nearMeeteetse, Wyoming. If proven efficacious, the vaccine could help agencies and stakeholder cooperators maintain specificpopulations of prairie dogs at robust levels, thus enhancing range-wide conservation of those species, as well recovery of the ferret,while enabling control of other prairie dog populations to resolve site-specific agricultural and human health concerns. The resultsof laboratory and field-testing in the early stages of developing this vaccine are preliminary but mostly encouraging. A plan forbroad-scale application is being developed for possible use when testing has been completed and (if warranted) the vaccine isregistered for governmental use. An overview of all aspects of the project is discussed.

  7. The insomnia plague: a Gabriel García Márquez story.

    Science.gov (United States)

    Sghirlanzoni, A; Carella, F

    2000-08-01

    "All the great writers have good eyes" is a sentence by V. Nabokov that is very suitable for G.G. Márquez and his One Hundred Years of Solitude. The novel, published in 1967, introduces among many others, the character of little Rebeca, whose frailness and greenish skin revealed hunger "that was older than she was". The girl, because of a pica syndrome, only liked to eat earth and the cake of whitewash. But her fate appears to be determined by the lethal insomnia plague, whose most fearsome part was not the impossibility of sleeping but its inexorable evolution toward a loss of memory in which the sick person "sinks into a kind of idiocy that had no past". Rebeca's lethal insomnia looks quite similar to the "peculiar, fatal disorder of sleep" originally described by Lugaresi et al. in 1986. One Hundred Years (of Solitude shows that G.G. Márquez was gifted not only with good eyes, but has the seductive power of changing reality into fantasy, while transforming his visions into reality.

  8. Manipulation of Interleukin-1β and Interleukin-18 Production by Yersinia pestis Effectors YopJ and YopM and Redundant Impact on Virulence.

    Science.gov (United States)

    Ratner, Dmitry; Orning, M Pontus A; Starheim, Kristian K; Marty-Roix, Robyn; Proulx, Megan K; Goguen, Jon D; Lien, Egil

    2016-05-06

    Innate immunity plays a central role in resolving infections by pathogens. Host survival during plague, caused by the Gram-negative bacterium Yersinia pestis, is favored by a robust early innate immune response initiated by IL-1β and IL-18. These cytokines are produced by a two-step mechanism involving NF-κB-mediated pro-cytokine production and inflammasome-driven maturation into bioactive inflammatory mediators. Because of the anti-microbial effects induced by IL-1β/IL-18, it may be desirable for pathogens to manipulate their production. Y. pestis type III secretion system effectors YopJ and YopM can interfere with different parts of this process. Both effectors have been reported to influence inflammasome caspase-1 activity; YopJ promotes caspase-8-dependent cell death and caspase-1 cleavage, whereas YopM inhibits caspase-1 activity via an incompletely understood mechanism. However, neither effector appears essential for full virulence in vivo Here we report that the sum of influences by YopJ and YopM on IL-1β/IL-18 release is suppressive. In the absence of YopM, YopJ minimally affects caspase-1 cleavage but suppresses IL-1β, IL-18, and other cytokines and chemokines. Importantly, we find that Y. pestis containing combined deletions of YopJ and YopM induces elevated levels of IL-1β/IL-18 in vitro and in vivo and is significantly attenuated in a mouse model of bubonic plague. The reduced virulence of the YopJ-YopM mutant is dependent on the presence of IL-1β, IL-18, and caspase-1. Thus, we conclude that Y. pestis YopJ and YopM can both exert a tight control of host IL-1β/IL-18 production to benefit the bacteria, resulting in a redundant impact on virulence. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Peste neumónica primaria con transmisión intrahospitalaria en La Libertad, Perú 2010 Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010

    Directory of Open Access Journals (Sweden)

    Luis F. Donaires

    2010-09-01

    Full Text Available La peste neumónica es una forma clínica de peste, de baja frecuencia y alta letalidad, transmitida por la inhalación directa de Yersinia pestis proveniente de un animal o de persona a persona. Objetivo. Describir las características clínicas y epidemiológicas de los casos de un brote de peste neumónica primaria humana en el norte de Perú. Materiales y métodos. Se revisaron las historias clínicas de los casos confirmados de peste neumónica primaria presentados en un brote ocurrido en la región de La Libertad, en el mes de julio de 2010, asimismo, se efectuó la búsqueda e investigación de contactos. Resultados. Se identificó el caso índice y tres casos adicionales, de estos últimos, dos fueron infecciones intrahospitalarias relacionadas con el caso índice. La presentación clínica inicial se caracterizó por fiebre de inicio súbito, escalofríos, mialgias y dolor torácico y evolución en menos de 24 horas a hipotensión arterial y cianosis. El inicio del tratamiento específico varió de 2 a 12 días, observándose que los casos con inicio precoz de tratamiento tuvieron un mejor resultado clínico. La letalidad fue de 50% (2/4. Conclusión. Se evidenció la transmisión intrahospitalaria de peste neumónica en el Perú con manifestaciones graves y alta letalidad.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. Objective. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. Materials and methods. 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. Results. The index case was identified, as well as three additional cases, out of these, two were

  10. White plague-like coral disease in remote reefs of the Western Caribbean

    Directory of Open Access Journals (Sweden)

    Juan A Sánchez

    2010-05-01

    Full Text Available The health of coral reef communities has been decreasing over the last 50 years, due the negative effects of human activities combined with other natural processes. We present documentation of a White Plague Disease (WPD outbreak in the Serrana Bank, an isolated Western Caribbean atoll with presumably inexistent pollutant inputs from local human settlements. In addition, this study summarizes seven years of observations on diseased corals in the nearby island of San Andrés, which in contrast is one of the most populated islands of the Caribbean. There was a massive coral mortality in the atoll lagoon (14°27’53.24", 80°14’22.27" W, and 12m depth due to WPD on May 4 of 2003. Seventeen species were found dead or largely affected by the disease. The information resulting from GPS and manta-tow transects revealed that approximately 5.8ha of reticulate Montastraea spp. patch reefs were lethally affected by the disease in the atoll. On May 8 of the same year we observed and calculated a mean coral cover of 7.03% (SD± 2.44, a mean diseased coral tissue cover of 5.5% (SD± 1.1 and a 13.4% (SD± 8.05 of recently dead coral covered with a thin filamentous algae layer; approximately 73% of mortalities caused by the disease occurred before the end of the outbreak. A rough estimate of 18.9% in recent coral cover reduction can be attributed to WPD. This represents about 82% of the total coral cover decline since 1995. Semi-enclosed environments such as atoll lagoons and the reticulate patch-reefs of Montastraea spp. seem to be particularly vulnerable to this kind of coral disease, which constitute an alert to increase the monitoring of the same kind of atoll environments. The WPD has been present in the area of the nearby island of San Andrés at a low prevalence level, with sporadic increasing peaks of disease proliferation. The peaks observed during 1999 and 2004 comprised increases of 266% and 355% respectively, suggesting an alarming progression of

  11. [New nutrient medium for the cultivation and isolation of the plague microbe ChDS-37 as an element of the mobilization reserve of specialized antiepidemic teams of the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare].

    Science.gov (United States)

    Mazrukho, A B; Kaminskiĭ, D I; Lomov, Yu M; Telesmanich, N P; Rozhkov, K K; Alutin, I M; Pukhov, Yu M; Prometnoĭ, V I; Fetsaĭlova, O P; Bulakhova, O G; Firsova, I A; Smolikova, L M; Bozhko, N V; Ivanova, V S; Burlakova, O S; Verkina, L M; Trukhachev, A L; Akulova, M V

    2011-04-01

    A new nutrient medium has been designed to culture and isolate the plague microbe ChDS-37 on the basis of the pancreatic digest of baker's yeast. The results of laboratory tests of the designed medium, by using 10 plague microbe strains and those of approval during the tactical and special training of a specialized antiepidemic team (SAET), suggest that the medium has some advantage over reference media and creates prerequisites for being incorporated into the mobilization reserve of a SAET.

  12. Complete Genome Sequence of Yersinis pestis Strains Antiqua and Nepa1516: Evidence of Gene Reduction in an Emerging Pathogen

    Energy Technology Data Exchange (ETDEWEB)

    Chain, Patrick S [ORNL; Hu, Ping [Lawrence Berkeley National Laboratory (LBNL); Malfatti, Stephanie [Lawrence Livermore National Laboratory (LLNL); Radnedge, Lyndsay [Lawrence Livermore National Laboratory (LLNL); Larimer, Frank W [ORNL; Vergez, Lisa [Lawrence Livermore National Laboratory (LLNL); Worsham, Patricia [U.S. Army Medical Research Institute of Infectious Diseases; Chu, May C [Centers for Disease Control and Prevention; Anderson, Gary L [Lawrence Berkeley National Laboratory (LBNL)

    2006-01-01

    Yersinia pestis, the causative agent of bubonic and pneumonic plagues, has undergone detailed study at the molecular level. To further investigate the genomic diversity among this group and to help characterize lineages of the plague organism that have no sequenced members, we present here the genomes of two isolates of the ''classical'' antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua and Nepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open reading frames, respectively. Though both strains belong to one of the three classical biovars, they represent separate lineages defined by recent phylogenetic studies. We compare all five currently sequenced Y. pestis genomes and the corresponding features in Yersinia pseudotuberculosis. There are strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. We found 453 single nucleotide polymorphisms in protein-coding regions, which were used to assess the evolutionary relationships of these Y. pestis strains. Gene reduction analysis revealed that the gene deletion processes are under selective pressure, and many of the inactivations are probably related to the organism's interaction with its host environment. The results presented here clearly demonstrate the differences between the two biovar antiqua lineages and support the notion that grouping Y. pestis strains based strictly on the classical definition of biovars (predicated upon two biochemical assays) does not accurately reflect the phylogenetic relationships within this species. A comparison of four virulent Y. pestis strains with the human-avirulent strain 91001 provides further insight into the genetic basis of virulence to humans.

  13. EKTOPARASIT (FLEAS PADA RESERVOIR DI DAERAH FOKUS PEST DI KABUPATEN BOYOLALI PROVINSI JAWA TENGAH

    Directory of Open Access Journals (Sweden)

    Tri Ramadhani

    2016-09-01

    Full Text Available ABSTRACTRat is a rodent (rodensia which cannot be separated from parasitic organism attacks the ectoparasites(fleas. In the presence of fleas plague focus areas need to watch out, for no increase in cases of plague(outbreak. Pest is a zoonosis in rat that can be transmitted to humans through the bite of fleas Xenopsyllacheopsis containing Yersinia pestis. Boyolali District is one of the plague focus areas in Central Java. Thisstudy aims to identify the species of rats and fleas, trap succes, flea infestation in rats and flea index as anindicator of vulnerability to transmission of plague. The study is a descriptive survey with cross sectionaldesign. The population is all the rats and fleas in Boyolali district. Samples are rats and fleas that werecaught using live trap with coconut roasted and salted fish is placed inside and outside the home (each 2trap. Rat combed for fleas. The results showed the number of mouses caught were 245. There are 4 speciesrats and small mammals found in R. tanezumi, R. tiomanicus, R. exulans, N. fulvescens and S.murinus withsucces trap at 5.71%. Only 3 species and S.murinus of infected fleas. Species of flea is X. cheopis and S.cognatus. Specific flea index: Xenopsylla cheopis by 1.67; flea index cognatus Stavilus common flea indexof 0.88 and 2.55. Based on the warning system indicator about the bubonic plague spreading,which isspecific flea index of X.cheopis >1 and fleas index >2, Selo sub distric should be aware to the spreading ofbubonic plague in its area, so that it is important to carry out the controlling of rat and flea population.Keyword: ectoparasite, reservoir, fleas, plague. ABSTRAK Tikus adalah hewan mengerat (rodensiayang tidak lepas dari serangan organisme parasit yaitu ektoparasit (pinjal.Pada daerah fokus pestt keberadaan pinjal perlu diwaspadai,agar tidak terjadi peningkatan kasus pestt (KLB. Pest merupakan zoonosispada tikusyang dapat ditularkan kepada manusia melalui gigitan pinjal Xenopsylla

  14. The influence of the growth conditions of the plague microbe vaccine strain colonies on the fractal dimension of biospeckles

    International Nuclear Information System (INIS)

    Ul'yanov, A S; Lyapina, A M; Ulianova, O V; Fedorova, V A; Uianov, S S

    2011-01-01

    Specific statistical characteristics of biospeckles, emerging under the diffraction of coherent beams on the bacterial colonies, are studied. The dependence of the fractal dimensions of biospeckles on the conditions of both illumination and growth of the colonies is studied theoretically and experimentally. Particular attention is paid to the fractal properties of biospeckles, emerging under the scattering of light by the colonies of the vaccinal strain of the plague microbe. The possibility in principle to classify the colonies of Yersinia pestis EV NIIEG using the fractal dimension analysis is demonstrated. (optical technologies in biophysics and medicine)

  15. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

    Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

  16. 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.

  17. Public Heath in Colonial and Post-Colonial Ghana: Lesson-Drawing for The Twenty-First Century

    Directory of Open Access Journals (Sweden)

    Adu-Gyamfi, Samuel

    2017-06-01

    Full Text Available Public health in twenty-first century Ghana is mired with several issues ranging from the inadequacy of public health facilities, improper settlement planning, insanitary conditions, and the inadequacy of laws and their implementation. This situation compared to the colonial era is a direct contradiction. Development in the pre-colonial era to the colonial era sought to make the prevention of diseases a priority in the colonial administration. This was begun with the establishment of the health branch in 1909 as a response to the bubonic plague that was fast spreading in the colony. From here public health policies and strategies were enacted to help the diseases prevention cause. Various public health boards, the medical research institute or the laboratory branch, the waste management department, the use of preventive medicine and maintenance of good settlement planning and sanitation were public health measures in the colonial era. This research seeks to analyse the public health system in the colonial era so as to draw basic lessons for twenty-first century Ghana. Archival data and other secondary sources are reviewed and analysed to help draw these lessons. Richard Rose’s lesson-drawing approach was used to draw the lessons.

  18. Yersinia virulence factors - a sophisticated arsenal for combating host defences [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steve Atkinson

    2016-06-01

    Full Text Available The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

  19. The Work of US Public Health Service Officers in Puerto Rico, 1898-1919.

    Science.gov (United States)

    Rigau-Pérez, Jose G

    2017-09-01

    The history of the US Public Health Service (PHS) is usually presented in terms of diseases or discoveries; this article examines twenty years' activity in one location. When the United States invaded Puerto Rico in 1898, the Marine Hospital Service (now PHS) took responsibility for foreign quarantine, inspection of immigrants, and medical care for merchant seamen. Its officers evaluated the sanitary conditions of port cities, helped reorganize local disease surveillance and control, and investigated endemic diseases (e.g., hookworm-related anemia) and epidemics (e.g., bubonic plague). After World War I and pandemic influenza, and the greater self-government allowed Puerto Rico by Congress in 1917, PHS officers withdrew from routine local sanitary actions. A narrow geographic focus (Puerto Rico), to examine PHS activity over time (1898 to 1919) provides a richer picture of the agency's impact, and reveals how the sum of disease control activities affected the development of an area's health status and institutions. The duties and, importantly, the personal initiatives of PHS officers in Puerto Rico, such as WW King, produced lasting impact on scientific institutions and administrative, professional, and health care practices.

  20. Three-dimensional structures of unligated uridine phosphorylase from Yersinia pseudotuberculosis at 1.4 Å resolution and its complex with an antibacterial drug

    Science.gov (United States)

    Balaev, V. V.; Lashkov, A. A.; Gabdulkhakov, A. G.; Dontsova, M. V.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

    2015-07-01

    Uridine phosphorylases play an essential role in the cellular metabolism of some antibacterial agents. Acute infectious diseases (bubonic plague, yersiniosis, pseudotuberculosis, etc., caused by bacteria of the genus Yersinia) are treated using both sulfanilamide medicines and antibiotics, including trimethoprim. The action of an antibiotic on a bacterial cell is determined primarily by the character of its interactions with cellular components, including those which are not targets (for example, with pyrimidine phosphorylases). This type of interaction should be taken into account in designing drugs. The three-dimensional structure of uridine phosphorylase from the bacterium Yersinia pseudotuberculosis ( YptUPh) with the free active site was determined for the first time by X-ray crystallography and refined at 1.40 Å resolution (DPI = 0.062 Å; ID PDB: 4OF4). The structure of the complex of YptUPh with the bacteriostatic drug trimethoprim was studied by molecular docking and molecular dynamics methods. The trimethoprim molecule was shown to be buffered by the enzyme YptUPh, resulting in a decrease in the efficiency of the treatment of infectious diseases caused by bacteria of the genus Yersinia with trimethoprim.

  1. Yersinia pestis strains of ancient phylogenetic branch 0.ANT are widely spread in the high-mountain plague foci of Kyrgyzstan.

    Science.gov (United States)

    Eroshenko, Galina A; Nosov, Nikita Yu; Krasnov, Yaroslav M; Oglodin, Yevgeny G; Kukleva, Lyubov M; Guseva, Natalia P; Kuznetsov, Alexander A; Abdikarimov, Sabyrzhan T; Dzhaparova, Aigul K; Kutyrev, Vladimir V

    2017-01-01

    Fifty six Yersinia pestis strains, isolated over the period of more than 50 years in three high-mountain foci of Kyrgyzstan (Tien Shan, Alai, and Talas), have been characterized by means of PCR and single nucleotide polymorphism (SNP) typing methods. Seven of these strains were also characterized by means of whole genome sequencing and genome-wide SNP phylogenetic analysis. It was found that forty two strains belong to 0.ANT2, 0.ANT3 and 0.ANT5 phylogenetic branches. From these, strains of 0.ANT2 and 0.ANT3 branches were earlier detected in China only, whereas 0.ANT5 phylogenetic branch was identified for Y. pestis phylogeny for the first time. According to the results of genome-wide SNP analysis, 0.ANT5 strains are ones of the most closely related to Y. pestis strain responsible for the Justinianic Plague. We have also found out that four of the studied strains belong to the phylogenetic branch 2.MED1, and ten strains from Talas high-mountain focus belong to the phylogenetic branch 0.PE4 (sub-branch 0.PE4t). Established diversity of Y. pestis strains and extensive dissemination of the strains pertaining to the 0.ANT branch confirm the antiquity of the mentioned above plague foci and suggest that strains of the 0.ANT branch, which serve as precursors for all highly virulent Y. pestis strains, had their origin in the Tien Shan mountains.

  2. Estratègia de control biològic de plagues en plantacions comercials de pomera en un sistema de malla tancada

    OpenAIRE

    Pages Mas, Pere

    2017-01-01

    Abstract The presence of chemical residues on fruits and the possible impact on the agricultural ecosystem and human health is increasingly encouraging the restriction of phytosanitary products of chemical synthesis. This is the reason why in this work it is performed a practical test on the application of alternative methods from the conventional insecticides to fight the main plagues of the apple tree and it performed in two exploitation of apple trees in the region of the Baix Emporda The ...

  3. 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.

  4. RNA-seq comparative analysis of Peking ducks spleen gene expression 24 h post-infected with duck plague virulent or attenuated virus.

    Science.gov (United States)

    Liu, Tian; Cheng, Anchun; Wang, Mingshu; Jia, Renyong; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Zhu, Dekang; Chen, Shun; Liu, Mafeng; Zhao, XinXin; Chen, Xiaoyue

    2017-09-13

    Duck plague virus (DPV), a member of alphaherpesvirus sub-family, can cause significant economic losses on duck farms in China. DPV Chinese virulent strain (CHv) is highly pathogenic and could induce massive ducks death. Attenuated DPV vaccines (CHa) have been put into service against duck plague with billions of doses in China each year. Researches on DPV have been development for many years, however, a comprehensive understanding of molecular mechanisms underlying pathogenicity of CHv strain and protection of CHa strain to ducks is still blank. In present study, we performed RNA-seq technology to analyze transcriptome profiling of duck spleens for the first time to identify differentially expressed genes (DEGs) associated with the infection of CHv and CHa at 24 h. Comparison of gene expression with mock ducks revealed 748 DEGs and 484 DEGs after CHv and CHa infection, respectively. Gene pathway analysis of DEGs highlighted valuable biological processes involved in host immune response, cell apoptosis and viral invasion. Genes expressed in those pathways were different in CHv infected duck spleens and CHa vaccinated duck spleens. The results may provide valuable information for us to explore the reasons of pathogenicity caused by CHv strain and protection activated by CHa strain.

  5. Profiles in medical courage: Joseph Goldberger, the sharecropper’s plague, science and prejudice

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2012-06-01

    Full Text Available No abstract available. Article truncated at 150 words. “You must accept the truth from whatever source it comes”. -MaimonidesThe Sharecropper’s PlagueIn the early half of the twentieth century a mysterious disease, “the sharecropper’s plague”, reached epidemic proportions in the Southern US (1. Each state decided whether it would recognize and publicly admit the existence of what was then considered an embarrassment. The total number of new annual cases was estimated as about 75,000 in 1915 and about 100,000 throughout the 1920s (2. The disease had a 40% mortality rate, and many survivors with dementia were confined to mental institutions (3. Patients initially presented with symmetrically reddened skin, similar to that produced by a sunburn or poison oak. Later, the dermatitis turned rough and scaly in one or more locations, such as the hands, the tops of the feet, or the ankles, or in a butterfly-shaped distribution across the nose. Disturbances of the digestive tract and the …

  6. Estimation of stochastic frontier models with fixed-effects through Monte Carlo Maximum Likelihood

    NARCIS (Netherlands)

    Emvalomatis, G.; Stefanou, S.E.; Oude Lansink, A.G.J.M.

    2011-01-01

    Estimation of nonlinear fixed-effects models is plagued by the incidental parameters problem. This paper proposes a procedure for choosing appropriate densities for integrating the incidental parameters from the likelihood function in a general context. The densities are based on priors that are

  7. New alternatives in the control of plagues and projections of the ICA in the handling of the residuals in agricultural products; Agriculturas alternativas: Enfasis en aportes de gente de campo del sector suroccidental de Colombia

    Energy Technology Data Exchange (ETDEWEB)

    Clavijo Navarro, P E

    1995-07-01

    The strategies are described indicated by the ICA for the control of plagues and of toxic residuals of agro-chemicals in the agricultural products, with emphasis in the implementation of mechanisms like the integrated control of plagues. It stands out the paper of the bio-insecticides as alternative to the agro-chemicals use and enter these stable products they are mentioned with the help of Bacillus thuringiensis, Beauveria bassiana, Nomuraea rileyi, Metarhizium anisoplidae and Verticilium lecanni. Some implications of the presence of toxic residuals are mentioned in Colombian export fruits and the measures that have been adopted to avoid them, as well as some mechanisms adopted in the international environment with the same end. The effective legislation is indicated as for prohibition and restriction of plaguicides use.

  8. The Fate of a Healing Goddess: Ocular Pathologies, the Antonine Plague, and the Ancient Roman Cult of Bona Dea

    Directory of Open Access Journals (Sweden)

    Leonardo Ambasciano

    2016-05-01

    Full Text Available The aim of this article is to offer a diachronic and dynamic contextualisation of the ancient Roman cult of Bona Dea, connecting its cognitive underpinnings with its healing dimension. Special attention is devoted to the ocular concerns attested in the epigraphic inventory. The decline of the presence of Bona Dea on the religious scene, attested by the 3rd century CE, is considered to be the multi-causal result of the long-lasting, ocular side-effects of smallpox in the aftermath of the so-called Antonine Plague, which interacted with the correlated and prolonged lack of positive reinforcement concerning symptom relief and cognitive feedback.

  9. Plague surveillance in Brazil: 1983 - 1992 Vigilância sorológica da peste no Brasil no período de 1983 a 1992

    Directory of Open Access Journals (Sweden)

    Alzira Maria Paiva de Almeida

    1995-12-01

    Full Text Available Plague caused by Yersinia pestis, has persisted in Brazil in several natural foci spread throughout rural areas in the States of Ceara, Paraiba, Pernambuco, Piaui, Rio Grande do Norte, Alagoas, Bahia, Minas Gerais and Rio de Janeiro. Nationwide surveillance of plague in Brazil based on serological testing started in 1983. We now present an update report of the examinations carried out in our laboratory from 1983 to 1992. The passive hemagglutination test for antibodies against fraction 1A antigen of Y. pestis and the passive hemagglutination inhibition control were employed for testing a total of 220,769 sera. Samples analyzed included 2,856 sera from clinically diagnosed plague cases or suspects, 49,848 sera from rodents of 24 species and 2 species of small wild carnivores (marsupials, 122,890 sera from dogs, and 45,175 sera from cats. Specific antibodies were found in 92 (3.22% human sera; 143 (0.29% sera from rodents of 8 species and from the two species of marsupials, 1,105 (0.90% sera from dogs and 290 (0.64% sera from cats. The presence of significant levels of specific anti-F1A antibodies among rodents and wild or domestic carnivores (dogs and cats indicates that all the Brazilian plague foci remain active in spite of the absence of human cases in some of them.A peste, infecção pela Yersinia pestis, se mantém no Brasil, em vários focos naturais, disseminados na área rural, dos Estados do Ceará, Paraiba, Pernambuco, Piaui, Rio Grande do Norte, Alagoas, Bahia, Minas Gerais e Rio de Janeiro. Desde 1983, o teste de hemaglutinação passiva para anticorpos contra a fração antigênica "F1A" de Y. pestis, vem sendo empregado ininterruptamente na vigilância da peste nos focos brasileiros. A especificidade do PHA é controlada pelo teste de inibição da aglutinação. No período de 1983 à 1992 foram examinadas 220.769 amostras de soro, sendo 2.856 de origem humana, 49.848 de roedores pertencentes à 24 espécies e de 2 espécies de

  10. Dissemination of a highly virulent pathogen: tracking the early events that define infection.

    Directory of Open Access Journals (Sweden)

    Rodrigo J Gonzalez

    2015-01-01

    Full Text Available The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of Yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1 do the bacteria encounter barriers in disseminating to draining lymph nodes (LN, and (2 what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by Y. pestis to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response

  11. Znu is the predominant zinc importer in Yersinia pestis during in vitro growth but is not essential for virulence.

    Science.gov (United States)

    Desrosiers, Daniel C; Bearden, Scott W; Mier, Ildefonso; Abney, Jennifer; Paulley, James T; Fetherston, Jacqueline D; Salazar, Juan C; Radolf, Justin D; Perry, Robert D

    2010-12-01

    Little is known about Zn homeostasis in Yersinia pestis, the plague bacillus. The Znu ABC transporter is essential for zinc (Zn) uptake and virulence in a number of bacterial pathogens. Bioinformatics analysis identified ZnuABC as the only apparent high-affinity Zn uptake system in Y. pestis. Mutation of znuACB caused a growth defect in Chelex-100-treated PMH2 growth medium, which was alleviated by supplementation with submicromolar concentrations of Zn. Use of transcriptional reporters confirmed that Zur mediated Zn-dependent repression and that it can repress gene expression in response to Zn even in the absence of Znu. Virulence testing in mouse models of bubonic and pneumonic plague found only a modest increase in survival in low-dose infections by the znuACB mutant. Previous studies of cluster 9 (C9) transporters suggested that Yfe, a well-characterized C9 importer for manganese (Mn) and iron in Y. pestis, might function as a second, high-affinity Zn uptake system. Isothermal titration calorimetry revealed that YfeA, the solute-binding protein component of Yfe, binds Mn and Zn with comparably high affinities (dissociation constants of 17.8 ± 4.4 nM and 6.6 ± 1.2 nM, respectively), although the complete Yfe transporter could not compensate for the loss of Znu in in vitro growth studies. Unexpectedly, overexpression of Yfe interfered with the znu mutant's ability to grow in low concentrations of Zn, while excess Zn interfered with the ability of Yfe to import iron at low concentrations; these results suggest that YfeA can bind Zn in the bacterial cell but that Yfe is incompetent for transport of the metal. In addition to Yfe, we have now eliminated MntH, FetMP, Efe, Feo, a substrate-binding protein, and a putative nickel transporter as the unidentified, secondary Zn transporter in Y. pestis. Unlike other bacterial pathogens, Y. pestis does not require Znu for high-level infectivity and virulence; instead, it appears to possess a novel class of transporter

  12. Plague bacterium as a transformer species in prairie dogs and the grasslands of western North America.

    Science.gov (United States)

    Eads, David A; Biggins, Dean E

    2015-08-01

    Invasive transformer species change the character, condition, form, or nature of ecosystems and deserve considerable attention from conservation scientists. We applied the transformer species concept to the plague bacterium Yersinia pestis in western North America, where the pathogen was introduced around 1900. Y. pestis transforms grassland ecosystems by severely depleting the abundance of prairie dogs (Cynomys spp.) and thereby causing declines in native species abundance and diversity, including threatened and endangered species; altering food web connections; altering the import and export of nutrients; causing a loss of ecosystem resilience to encroaching invasive plants; and modifying prairie dog burrows. Y. pestis poses an important challenge to conservation biologists because it causes trophic-level perturbations that affect the stability of ecosystems. Unfortunately, understanding of the effects of Y. pestis on ecosystems is rudimentary, highlighting an acute need for continued research. © 2015 Society for Conservation Biology.

  13. Plague bacterium as a transformer species in prairie dogs and the grasslands of western North America

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.

    2015-01-01

    Invasive transformer species change the character, condition, form, or nature of ecosystems and deserve considerable attention from conservation scientists. We applied the transformer species concept to the plague bacterium Yersinia pestis in western North America, where the pathogen was introduced around 1900. Y. pestis transforms grassland ecosystems by severely depleting the abundance of prairie dogs (Cynomys spp.) and thereby causing declines in native species abundance and diversity, including threatened and endangered species; altering food web connections; altering the import and export of nutrients; causing a loss of ecosystem resilience to encroaching invasive plants; and modifying prairie dog burrows. Y. pestis poses an important challenge to conservation biologists because it causes trophic-level perturbations that affect the stability of ecosystems. Unfortunately, understanding of the effects of Y. pestis on ecosystems is rudimentary, highlighting an acute need for continued research.

  14. The Effects of Low-Shear Mechanical Stress on Yersinia pestis Virulence

    Science.gov (United States)

    Lawal, Abidat; Jejelowo, Olufisayo A.; Rosenzweig, Jason A.

    2010-11-01

    Manned space exploration has created a need to evaluate the effects of spacelike stress on pathogenic and opportunistic microbes astronauts could carry with them to the International Space Station and beyond. Yersinia pestis (YP) causes bubonic, septicemic, and pneumonic plague and is capable of killing infected patients within 3-7 days. In this study, low-shear modeled microgravity (LSMMG), a spacelike stress, was used to physically stress YP; and its effects on proliferation, cold growth, and type III secretion system (T3SS) function were evaluated. YP was grown to saturation in either LSMMG or normal gravity (NG) conditions prior to being used for RAW 246.7 cell infections, HeLa cell infections, and Yop secretion assays. A mutant strain of YP (ΔyopB) that lacks the ability to inject Yersinia outer membrane proteins (Yops) into the host cell was used as a negative control in cell infection experiments. Our experimental results indicate that YP cultivated under LSMMG resulted in reduced YopM production and secretion compared to its NG-grown counterpart. Similarly, NG-grown YP induced more cell rounding in HeLa cells than did the LSMMG-grown YP, which suggests that LSMMG somehow impairs T3SS optimum function. Also, LSMMG-grown YP used to infect cultured RAW 246.7 cells showed a similar pattern of dysfunction in that it proliferated less than did its NG-grown counterpart during an 8-hour infection period. This study suggests that LSMMG can attenuate bacterial virulence contrary to previously published data that have demonstrated LSMMG-induced hypervirulence of other Gram-negative enterics.

  15. Fowl plague virus replication in mammalian cell-avian erythrocyte heterokaryons: studies concerning the actinomycin D and ultra-violet lig sensitive phase in influenza virus replication

    International Nuclear Information System (INIS)

    Kelly, D.C.; Dimmock, N.J.

    1974-01-01

    The replication of fowl plague virus in BHK and L cells specifically blocked prior to infection with inhibitors of influenza virus replication (actinomycin D and ultraviolet light irradiation) has been studied by the introduction of a metabolically dormant avian erythrocyte nucleus. This permits the synthesis of just the influenza virus nucleoprotein in actinomycin D (but not ultraviolet light) blocked cells. The NP antigen is first detected in the avian erythrocyte nucleus and subsequently in the heterokaryon cytoplasm

  16. Challenges to assessing connectivity between massive populations of the Australian plague locust

    Science.gov (United States)

    Chapuis, Marie-Pierre; Popple, Julie-Anne M.; Berthier, Karine; Simpson, Stephen J.; Deveson, Edward; Spurgin, Peter; Steinbauer, Martin J.; Sword, Gregory A.

    2011-01-01

    Linking demographic and genetic dispersal measures is of fundamental importance for movement ecology and evolution. However, such integration can be difficult, particularly for highly fecund species that are often the target of management decisions guided by an understanding of population movement. Here, we present an example of how the influence of large population sizes can preclude genetic approaches from assessing demographic population structuring, even at a continental scale. The Australian plague locust, Chortoicetes terminifera, is a significant pest, with populations on the eastern and western sides of Australia having been monitored and managed independently to date. We used microsatellites to assess genetic variation in 12 C. terminifera population samples separated by up to 3000 km. Traditional summary statistics indicated high levels of genetic diversity and a surprising lack of population structure across the entire range. An approximate Bayesian computation treatment indicated that levels of genetic diversity in C. terminifera corresponded to effective population sizes conservatively composed of tens of thousands to several million individuals. We used these estimates and computer simulations to estimate the minimum rate of dispersal, m, that could account for the observed range-wide genetic homogeneity. The rate of dispersal between both sides of the Australian continent could be several orders of magnitude lower than that typically considered as required for the demographic connectivity of populations. PMID:21389030

  17. Characterizing the reproduction number of epidemics with early subexponential growth dynamics.

    Science.gov (United States)

    Chowell, Gerardo; Viboud, Cécile; Simonsen, Lone; Moghadas, Seyed M

    2016-10-01

    Early estimates of the transmission potential of emerging and re-emerging infections are increasingly used to inform public health authorities on the level of risk posed by outbreaks. Existing methods to estimate the reproduction number generally assume exponential growth in case incidence in the first few disease generations, before susceptible depletion sets in. In reality, outbreaks can display subexponential (i.e. polynomial) growth in the first few disease generations, owing to clustering in contact patterns, spatial effects, inhomogeneous mixing, reactive behaviour changes or other mechanisms. Here, we introduce the generalized growth model to characterize the early growth profile of outbreaks and estimate the effective reproduction number, with no need for explicit assumptions about the shape of epidemic growth. We demonstrate this phenomenological approach using analytical results and simulations from mechanistic models, and provide validation against a range of empirical disease datasets. Our results suggest that subexponential growth in the early phase of an epidemic is the rule rather the exception. Mechanistic simulations show that slight modifications to the classical susceptible-infectious-removed model result in subexponential growth, and in turn a rapid decline in the reproduction number within three to five disease generations. For empirical outbreaks, the generalized-growth model consistently outperforms the exponential model for a variety of directly and indirectly transmitted diseases datasets (pandemic influenza, measles, smallpox, bubonic plague, cholera, foot-and-mouth disease, HIV/AIDS and Ebola) with model estimates supporting subexponential growth dynamics. The rapid decline in effective reproduction number predicted by analytical results and observed in real and synthetic datasets within three to five disease generations contrasts with the expectation of invariant reproduction number in epidemics obeying exponential growth. The

  18. Characterizing the reproduction number of epidemics with early subexponential growth dynamics

    Science.gov (United States)

    Viboud, Cécile; Simonsen, Lone; Moghadas, Seyed M.

    2016-01-01

    Early estimates of the transmission potential of emerging and re-emerging infections are increasingly used to inform public health authorities on the level of risk posed by outbreaks. Existing methods to estimate the reproduction number generally assume exponential growth in case incidence in the first few disease generations, before susceptible depletion sets in. In reality, outbreaks can display subexponential (i.e. polynomial) growth in the first few disease generations, owing to clustering in contact patterns, spatial effects, inhomogeneous mixing, reactive behaviour changes or other mechanisms. Here, we introduce the generalized growth model to characterize the early growth profile of outbreaks and estimate the effective reproduction number, with no need for explicit assumptions about the shape of epidemic growth. We demonstrate this phenomenological approach using analytical results and simulations from mechanistic models, and provide validation against a range of empirical disease datasets. Our results suggest that subexponential growth in the early phase of an epidemic is the rule rather the exception. Mechanistic simulations show that slight modifications to the classical susceptible–infectious–removed model result in subexponential growth, and in turn a rapid decline in the reproduction number within three to five disease generations. For empirical outbreaks, the generalized-growth model consistently outperforms the exponential model for a variety of directly and indirectly transmitted diseases datasets (pandemic influenza, measles, smallpox, bubonic plague, cholera, foot-and-mouth disease, HIV/AIDS and Ebola) with model estimates supporting subexponential growth dynamics. The rapid decline in effective reproduction number predicted by analytical results and observed in real and synthetic datasets within three to five disease generations contrasts with the expectation of invariant reproduction number in epidemics obeying exponential growth. The

  19. A Numerical Modelling Study on the Potential Role of Tsunamis in the Biblical Exodus

    Directory of Open Access Journals (Sweden)

    José M. Abril

    2015-07-01

    Full Text Available The reliability of the narrative of the Biblical Exodus has been subject of heated debate for decades. Recent archaeological studies seem to provide new insight of the exodus path, and although with a still controversial chronology, the effects of the Minoan Santorini eruption have been proposed as a likely explanation of the biblical plagues. Particularly, it has been suggested that flooding by the associated tsunamis could explain the first plague and the sea parting. Recent modelling studies have shown that Santorini’s tsunami effects were negligible in the eastern Nile Delta, but the released tectonic stress could have triggered local tsunamigenic sources in sequence. This paper is aimed to a quantitative assessment of the potential role of tsunamis in the biblical parting of the sea. Several “best case” scenarios are tested through the application of a numerical model for tsunami propagation that has been previously validated. The former paleogeographic conditions of the eastern Nile Delta have been implemented based upon recent geological studies; and several feasible local sources for tsunamis are proposed. Tsunamis triggered by submarine landslides of 10–30 km3 could have severely impacted the northern Sinai and southern Levantine coasts but with weak effects in the eastern Nile Delta coastline. The lack of noticeable flooding in this area under the most favorable conditions for tsunamis, along with the time sequence of water elevations, make difficult to accept them as a plausible and literally explanation of the first plague and of the drowning of the Egyptian army in the surroundings of the former Shi-Hor Lagoon.

  20. Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys Gunnisoni) during plague outbreaks

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Cordova, Jennifer; Colman, Rebecca E.; Keim, Paul; Rocke, Tonie E.; Leid, Jeff G.; Van Pelt, William E.; Wagner, David M.

    2011-01-01

    Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison’s prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005–2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.

  1. The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis.

    Science.gov (United States)

    Bozue, Joel; Mou, Sherry; Moody, Krishna L; Cote, Christopher K; Trevino, Sylvia; Fritz, David; Worsham, Patricia

    2011-06-01

    At the genomic level, Yersinia pestis and Yersinia pseudotuberculosis are nearly identical but cause very different diseases. Y. pestis is the etiologic agent of plague; whereas Y. pseudotuberculosis causes a gastrointestinal infection primarily after the consumption of contaminated food. In many gram-negative pathogenic bacteria, PhoP is part of a two-component global regulatory system in which PhoQ serves as the sensor kinase, and PhoP is the response regulator. PhoP is known to activate a number of genes in many bacteria related to virulence. To determine the role of the PhoPQ proteins in Yersinia infections, primarily using aerosol challenge models, the phoP gene was deleted from the chromosome of the CO92 strain of Y. pestis and the IP32953 strain of Y. pseudotuberculosis, leading to a polar mutation of the phoPQ operon. We demonstrated that loss of phoPQ from both strains leads to a defect in intracellular growth and/or survival within macrophages. These in vitro data would suggest that the phoPQ mutants would be attenuated in vivo. However, the LD(50) for the Y. pestis mutant did not differ from the calculated LD(50) for the wild-type CO92 strain for either the bubonic or pneumonic murine models of infection. In contrast, mice challenged by aerosol with the Y. pseudotuberculosis mutant had a LD(50) value 40× higher than the wild-type strain. These results demonstrate that phoPQ are necessary for full virulence by aerosol infection with the IP32953 strain of Y. pseudotuberculosis. However, the PhoPQ proteins do not play a significant role in infection with a fully virulent strain of Y. pestis. Published by Elsevier India Pvt Ltd.

  2. Novel genetic tools for diaminopimelic acid selection in virulence studies of Yersinia pestis.

    Science.gov (United States)

    Bland, David M; Eisele, Nicholas A; Keleher, Lauren L; Anderson, Paul E; Anderson, Deborah M

    2011-03-02

    Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP) pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX) operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence.

  3. Novel genetic tools for diaminopimelic acid selection in virulence studies of Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    David M Bland

    2011-03-01

    Full Text Available Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence.

  4. The Resistance to Plague Infection among Meriones persicus from Endemic and Non-endemic Regions in Iran: The Role of Gut Microbiota

    Science.gov (United States)

    ASSMAR, Mehdi; KEYPOUR, Marjan; ROHANI, Mehdi; MOSTAFAVI, Ehsan; DANESHVAR FARHUD, Dariush

    2018-01-01

    Background: The present study was conducted approximately 40 years ago, but its results have not been released. At the time of this study, the importance of the gut microbiota was not fully understood. Methods: Meriones persicus rodents, as one of the major reservoirs of Yersinia pestis bacterium in Iran, were compared in a disease endemic area (Akanlu, Hamadan, western Iran) and a non-endemic zone (Telo, Tehran, Iran) from 1977 to 1981. Results: This study was able to transmit the resistance to Y. pestis to other rodents creatively by using and transferring gut microbiota. Conclusion: The study indicated for the first time that the gut microbiota could affect the sensitivity to plague in Meriones in Telo. PMID:29318122

  5. Preliminary Empirical Model of Crucial Determinants of Best Practice for Peer Tutoring on Academic Achievement

    Science.gov (United States)

    Leung, Kim Chau

    2015-01-01

    Previous meta-analyses of the effects of peer tutoring on academic achievement have been plagued with theoretical and methodological flaws. Specifically, these studies have not adopted both fixed and mixed effects models for analyzing the effect size; they have not evaluated the moderating effect of some commonly used parameters, such as comparing…

  6. Bacterial profiling of White Plague Disease in a comparative coral species framework.

    KAUST Repository

    Roder, Cornelia

    2014-01-01

    Coral reefs are threatened throughout the world. A major factor contributing to their decline is outbreaks and propagation of coral diseases. Due to the complexity of coral-associated microbe communities, little is understood in terms of disease agents, hosts and vectors. It is known that compromised health in corals is correlated with shifts in bacterial assemblages colonizing coral mucus and tissue. However, general disease patterns remain, to a large extent, ambiguous as comparative studies over species, regions, or diseases are scarce. Here, we compare bacterial assemblages of samples from healthy (HH) colonies and such displaying signs of White Plague Disease (WPD) of two different coral species (Pavona duerdeni and Porites lutea) from the same reef in Koh Tao, Thailand, using 16S rRNA gene microarrays. In line with other studies, we found an increase of bacterial diversity in diseased (DD) corals, and a higher abundance of taxa from the families that include known coral pathogens (Alteromonadaceae, Rhodobacteraceae, Vibrionaceae). In our comparative framework analysis, we found differences in microbial assemblages between coral species and coral health states. Notably, patterns of bacterial community structures from HH and DD corals were maintained over species boundaries. Moreover, microbes that differentiated the two coral species did not overlap with microbes that were indicative of HH and DD corals. This suggests that while corals harbor distinct species-specific microbial assemblages, disease-specific bacterial abundance patterns exist that are maintained over coral species boundaries.

  7. Second quantization approach to composite hadron interactions in quark models

    International Nuclear Information System (INIS)

    Hadjimichef, D.; Krein, G.; Veiga, J.S. da; Szpigel, S.

    1995-11-01

    Starting from the Fock space representation of hadron bound states in a quark model, a change of representation is implemented by a unitary transformation such that the composite hadrons are redescribed by elementary-particle field operators. Application of the unitary transformation to the microscopic quark Hamiltonian gives rise to effective hadron-hadron, hadron-quark, and quark-quark Hamiltonians. An effective baryon Hamiltonian is derived using a simple quark model. The baryon Hamiltonian is free of the post-prior discrepancy which usually plagues composite-particle effective interactions. (author). 13 refs., 1 fig

  8. Viagem(ns a Santos Journey(s to Santos

    Directory of Open Access Journals (Sweden)

    Henrique Luiz Cukierman

    1998-06-01

    Full Text Available O artigo busca lançar algumas luzes sobre a construção do laboratório de Manguinhos, recontando um de seus episódios precursores: a viagem a Santos empreendida em 1899 por Oswaldo Cruz, um jovem médico às vésperas de tornar-se herói nacional enquanto símbolo brasileiro da ciência. Destinada a confirmar a chegada pela primeira vez da famigerada peste bubônica em terras brasileiras, a viagem constituiria um marco na justificação da construção de uma fábrica de soro antipestoso no Rio de Janeiro, o futuro Instituto Soroterápico Federal, inaugurado em 1900 e no qual viria a ser instalado o embrião do laboratório de Manguinhos. A partir de quatro narrativas distintas, é possível verificar o processo de ‘criação do mundo’ através do qual cada uma delas realiza sua própria expansão do que seria aparentemente uma ‘mesma’ viagem, permitindo assim configurar a historicidade desses relatos.The article intends to shed some light on the creation of the Manguinhos laboratory by recounting an episode which predates it: the journey to Santos taken in 1899 by Oswaldo Cruz, a young physician about to become a national hero and the Brazilian symbol of science. Destined to confirm the arrival of the infamous bubonic plague in Brazil for the first time, this journey was a milestone in justifying construction of a factory to produce anti-plague serum in Rio de Janeiro - the future Instituto Soroterápico Federal, inaugurated in 1900 and later embryo of the Manguinhos laboratory. Four different narratives of this journey reveal different processes of ‘creating the world’, each arriving at its own interpretation of the same journey.

  9. Estudos bacteriológicos e sorológicos de um surto de peste no Estado da Paraíba, Brasil Bacteriological and serological studies of a plague outbreak in the Paraíba state, Brazil

    Directory of Open Access Journals (Sweden)

    Alzira Maria Paiva Almeida

    1989-06-01

    Full Text Available Foram realizados estudos bacteriológicos e/ou sorológicos para diagnóstico da infecção pestosa, em material obtido de 452 pacientes (48 positivos, 1.938 roedores e outros pequenos mamíferos (75 positivos, 4.756 cães (141 positivos e 3.047 gatos (57 positivos, oriundos de 41 municípios localizados em toda a extensão da área paraibana do Planalto da Borborema. A infecção foi encontrada em 21 municípios. Foram isoladas 20 cepas de Yersinia pestis de amostras coletadas de três pacientes e 17 roedores. Estas cepas apresentam características bioquímicas, fatores de virulência, sensibilidade aos antibióticos e poder patogênico experimental semelhantes ao de cepas isoladas anteriormente. Pelos estudos realizados não foram observados, no surto de peste que eclodiu em setembro de 1986 na Paraíba, fatores diferentes dos observados nos outros focos do nordeste do Brasil.During a plague outbreak in the Borborema Plateu focus (Paraíba, bacteriological and serological studies were carryed out in material from 452 patients (48 positives, 1,938 rodents and other small mammals (75 positives, 4,756 dogs (141 positives and 2,047 cats (57 positives obtained from 41 counties (out of which, 21 produced positive samples. Twenty Yersinia pestis strains isolated from material from 3 patients ans 17 rodents, displayed biochemical reactions, virulence factors, antibiotic susceptibility and animal experimental pathogenicity similar to those observed in strains previously isolated. According to our findings this recent plague outbreak did not exhibite different factors from those observed during prior outbreaks in other plague foci in the northeast of Brazil.

  10. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Science.gov (United States)

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Matthew D Dyer

    2010-08-01

    Full Text Available Bacillus anthracis, Francisella tularensis, and Yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as NIAID Category A priority pathogens for possible use as biological weapons. However, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion.In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions between human proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, we identified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactions including interactions involving 304 B. anthracis, 52 F. tularensis, and 330 Y. pestis proteins that are uncharacterized. Computational analysis revealed that pathogen proteins preferentially interact with human proteins that are hubs and bottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conserved amongst the three networks. Functionally, such conserved modules reveal commonalities between how the different pathogens interact with crucial host pathways involved in inflammation and immunity.These data constitute the first extensive protein interaction networks constructed for bacterial pathogens and their human hosts. This study provides novel insights into host-pathogen interactions.

  12. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    Energy Technology Data Exchange (ETDEWEB)

    Balaev, V. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2015-03-15

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R{sub work} = 16.2, R{sub free} = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

  13. Banting Memorial Lecture 2010^. Type 2 diabetes as an 'infectious' disease: is this the Black Death of the 21st century?

    Science.gov (United States)

    Matthews, D R; Matthews, P C

    2011-01-01

    We are currently facing a global pandemic of obesity and Type 2 diabetes. In some settings, the population prevalence of Type 2 diabetes is 50%, and half of those affected will die from diabetes-related complications. Eight centuries ago, an epidemic of bubonic plague swept across Europe, killing at least half of its victims. We here draw comparisons between these two pandemics, proposing close analogies between the 'Black Death' of the 14th century and the modern-day equivalent of Type 2 diabetes. Both diseases can be considered in terms of an aetiological agent, a reservoir, a vector and a predisposing toxic environment; populations can be considered as highly susceptible to the transmissable agents of Type 2 diabetes in the setting of calorie excess, inadequate food labelling, poorly regulated advertising and sedentary lifestyles. As for tackling a pandemic of a contagious microbial pathogen, we believe that breaking the cycle of transmission in the diabetes epidemic must be underpinned by political will and prompt, decisive legislation backed by the medical community. Far from fearing that such measures edge us towards a 'nanny state', we believe individuals should expect a responsible government to safeguard them from the toxic milieu that puts them at risk of obesity and its complications, and that communities and populations have the right to have their health protected. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

  14. Reading visual representations of 'Ndabeni' in the public realms

    Directory of Open Access Journals (Sweden)

    Sipokazi Sambumbu

    2010-11-01

    Full Text Available This essay outlines and analyses contemporary image representations of Ndabeni (also called kwa-Ndabeni, a location near Cape Town where a group of people became confined between 1901 and 1936 following an outbreak of the bubonic plague in the city. This location was to shape Cape Town's landscape for a little less that thirty-five years, accommodating people who were forcibly removed from the Cape Town docklands and from District Six. Images representing this place have been produced, archived, recovered, modified, reproduced and circulated in different ways and contexts. Ndabeni has become public knowledge through public visual representations that have been produced across a range of sites in post-apartheid Cape Town. I focus on three sites: the Victoria and Alfred Waterfront, the District Six Museum, and the Eziko Restaurant and Catering School. In each case I analyse the processes through which the Ndabeni images in question have been used and reused over time in changing contexts. I analyse the 'modalities' in which these images have been composed, interpreted and employed and in which knowledge has been mediated. I explore the contents and contexts of the storyboards and exhibition panels that purport to represent Ndabeni. Finally, I discuss potential meanings that could be constructed if the images could be read independent of the texts.

  15. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    International Nuclear Information System (INIS)

    Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

    2015-01-01

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh

  16. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    Science.gov (United States)

    Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

    2015-03-01

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis ( YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability ( R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

  17. Construction of a GeogDetector-based model system to indicate the potential occurrence of grasshoppers in Inner Mongolia steppe habitats.

    Science.gov (United States)

    Shen, J; Zhang, N; Gexigeduren; He, B; Liu, C-Y; Li, Y; Zhang, H-Y; Chen, X-Y; Lin, H

    2015-06-01

    Grasshopper plagues have seriously disturbed grassland ecosystems in Inner Mongolia, China. The accurate prediction of grasshopper infestations and control of grasshopper plagues have become urgent needs. We sampled 234, 342, 335, and 369 plots in Xianghuangqi County of Xilingol League in 2010, 2011, 2012, and 2013, respectively, and measured the density of the most dominant grasshopper species, Oedaleus decorus asiaticus, and the latitude, longitude, and associated relatively stable habitat factors at each plot. We used Excel-GeogDetector software to explore the effects of individual habitat factors and the two-factor interactions on grasshopper density. We estimated the membership of each grasshopper density rank and determined the weights of each habitat category. These results were used to construct a model system evaluating grasshopper habitat suitability. The results showed that our evaluation system was reliable and the fuzzy evaluation scores of grasshopper habitat suitability were good indicators of potential occurrence of grasshoppers. The effects of the two-factor interactions on grasshopper density were greater than the effects of any individual factors. O. d. asiaticus was most likely to be found at elevations of 1300-1400 m, flat terrain or slopes of 4-6°, typical chestnut soil with 70-80% sand content in the top 5 cm of soil, and medium-coverage grassland. The species preferred temperate bunchgrass steppe dominated by Stipa krylovii and Cleistogenes squarrosa. These findings may be used to improve models to predict grasshopper occurrence and to develop management guidelines to control grasshopper plagues by changing habitats.

  18. Variational solution of the Gross-Neveu model; 2, finite-N and renormalization

    CERN Document Server

    Arvanitis, C; Iacomi, M; Kneur, J L; Neveu, A

    1995-01-01

    We show how to perform systematically improvable variational calculations in the O(2N) Gross-Neveu model for generic N, in such a way that all infinities usually plaguing such calculations are accounted for in a way compatible with the renormalization group. The final point is a general framework for the calculation of non-perturbative quantities like condensates, masses, etc..., in an asymptotically free field theory. For the Gross-Neveu model, the numerical results obtained from a "two-loop" variational calculation are in very good agreement with exact quantities down to low values of N.

  19. Intramuscular Immunization of Mice with a Live-Attenuated Triple Mutant of Yersinia pestis CO92 Induces Robust Humoral and Cell-Mediated Immunity To Completely Protect Animals against Pneumonic Plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Ponnusamy, Duraisamy; Baze, Wallace B; Fitts, Eric C; Popov, Vsevolod L; van Lier, Christina J; Erova, Tatiana E; Chopra, Ashok K

    2015-12-01

    Earlier, we showed that the Δlpp ΔmsbB Δail triple mutant of Yersinia pestis CO92 with deleted genes encoding Braun lipoprotein (Lpp), an acyltransferase (MsbB), and the attachment invasion locus (Ail), respectively, was avirulent in a mouse model of pneumonic plague. In this study, we further evaluated the immunogenic potential of the Δlpp ΔmsbB Δail triple mutant and its derivative by different routes of vaccination. Mice were immunized via the subcutaneous (s.c.) or the intramuscular (i.m.) route with two doses (2 × 10(6) CFU/dose) of the above-mentioned triple mutant with 100% survivability of the animals. Upon subsequent pneumonic challenge with 70 to 92 50% lethal doses (LD(50)) of wild-type (WT) strain CO92, all of the mice survived when immunization occurred by the i.m. route. Since Ail has virulence and immunogenic potential, a mutated version of Ail devoid of its virulence properties was created, and the genetically modified ail replaced the native ail gene on the chromosome of the Δlpp ΔmsbB double mutant, creating a Δlpp ΔmsbB::ailL2 vaccine strain. This newly generated mutant was attenuated similarly to the Δlpp ΔmsbB Δail triple mutant when administered by the i.m. route and provided 100% protection to animals against subsequent pneumonic challenge. Not only were the two above-mentioned mutants cleared rapidly from the initial i.m. site of injection in animals with no histopathological lesions, the immunized mice did not exhibit any disease symptoms during immunization or after subsequent exposure to WT CO92. These two mutants triggered balanced Th1- and Th2-based antibody responses and cell-mediated immunity. A substantial increase in interleukin-17 (IL-17) from the T cells of vaccinated mice, a cytokine of the Th17 cells, further augmented their vaccine potential. Thus, the Δlpp ΔmsbB Δail and Δlpp ΔmsbB::ailL2 mutants represent excellent vaccine candidates for plague, with the latter mutant still retaining Ail immunogenicity but

  20. Differential control of Yersinia pestis biofilm formation in vitro and in the flea vector by two c-di-GMP diguanylate cyclases.

    Directory of Open Access Journals (Sweden)

    Yi-Cheng Sun

    2011-04-01

    Full Text Available Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE, encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in c-di-GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hms-independent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP and two DGCs (HmsT and Y3730 control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis.

  1. Modeling, Control and Coordination of Helicopter Systems

    CERN Document Server

    Ren, Beibei; Chen, Chang; Fua, Cheng-Heng; Lee, Tong Heng

    2012-01-01

    Modeling, Control and Coordination of Helicopter Systems provides a comprehensive treatment of helicopter systems, ranging from related nonlinear flight dynamic modeling and stability analysis to advanced control design for single helicopter systems, and also covers issues related to the coordination and formation control of multiple helicopter systems to achieve high performance tasks. Ensuring stability in helicopter flight is a challenging problem for nonlinear control design and development. This book is a valuable reference on modeling, control and coordination of helicopter systems,providing readers with practical solutions for the problems that still plague helicopter system design and implementation. Readers will gain a complete picture of helicopters at the systems level, as well as a better understanding of the technical intricacies involved. This book also: Presents a complete picture of modeling, control and coordination for helicopter systems Provides a modeling platform for a general class of ro...

  2. Multigroup models of the convective epoch in core collapse supernovae

    International Nuclear Information System (INIS)

    Swesty, F Douglas; Myra, Eric S

    2005-01-01

    Understanding the explosion mechanism of core collapse supernovae is a problem that has plagued nuclear astrophysicists since the first computational models of this phenomenon were carried out in the 1960s. Our current theories of this violent phenomenon center around multi-dimensional effects involving radiation-hydrodynamic flows of hot, dense matter and neutrinos. Modeling these multi-dimensional radiative flows presents a computational challenge that will continue to stress high-performance computing beyond the teraflops to the petaflop level. In this paper we describe a few of the scientific discoveries that we have made via terascale computational simulations of supernovae under the auspices of the SciDAC-funded Terascale Supernova Initiative

  3. Comparative efficacies of candidate antibiotics against Yersinia pestis in an in vitro pharmacodynamic model.

    Science.gov (United States)

    Louie, Arnold; Vanscoy, Brian; Liu, Weiguo; Kulawy, Robert; Brown, David; Heine, Henry S; Drusano, George L

    2011-06-01

    Yersinia pestis, the bacterium that causes plague, is a potential agent of bioterrorism. Streptomycin is the "gold standard" for the treatment of plague infections in humans, but the drug is not available in many countries, and resistance to this antibiotic occurs naturally and has been generated in the laboratory. Other antibiotics have been shown to be active against Y. pestis in vitro and in vivo. However, the relative efficacies of clinically prescribed regimens of these antibiotics with streptomycin and with each other for the killing of Yersinia pestis are unknown. The efficacies of simulated pharmacokinetic profiles for human 10-day clinical regimens of ampicillin, meropenem, moxifloxacin, ciprofloxacin, and gentamicin were compared with the gold standard, streptomycin, for killing of Yersinia pestis in an in vitro pharmacodynamic model. Resistance amplification with therapy was also assessed. Streptomycin killed the microbe in one trial but failed due to resistance amplification in the second trial. In two trials, the other antibiotics consistently reduced the bacterial densities within the pharmacodynamic systems from 10⁸ CFU/ml to undetectable levels (pestis and deserve further evaluation.

  4. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    Directory of Open Access Journals (Sweden)

    Michele La Merrill

    Full Text Available Dichlorodiphenyltrichloroethane (DDT has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

  5. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    Science.gov (United States)

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  6. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  7. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  8. Complete Genome Sequence of Yersinia pestis Strains Antiqua andNepal516: Evidence of Gene Reduction in an Emerging Pathogen

    Energy Technology Data Exchange (ETDEWEB)

    Chain, Patrick S.G.; Hu, Ping; Malfatti, Stephanie A.; Radnedge,Lyndsay; Larimer, Frank; Vergez, Lisa M.; Worsham, Patricia; Chu, May C.; Andersen, Gary L.

    2006-01-16

    Yersinia pestis, the causative agent of bubonic andpneumonicplague, has undergone detailed study at the molecular level. Tofurther investigate the genomic diversity among this group and to helpcharacterize lineages of the plague organism that have no sequencedmembers, we present here the genomes of two isolates of the "classical"Antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua andNepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open readingframes respectively. Though both strains belong to one of the threeclassical biovars, they represent separate lineages defined by recentphylogenetic studies. We compare all five currently sequenced Y. pestisgenomes and the corresponding features in Y. pseudotuberculosis. Thereare strain-specific rearrangements, insertions, deletions, singlenucleotide polymorphisms and a unique distribution of insertionsequences. We found 453 single nucleotide polymorphisms in protein codingregions, which were used to assess evolutionary relationships of these Y.pestis strains. Gene reduction analysis revealed that the gene deletionprocesses are under selective pressure and many of the inactivations areprobably related to the organism s interaction with its host environment.The results presented here clearly demonstrate the differences betweenthe two Antiqua lineages and support the notion that grouping Y. pestisstrains based strictly on the classical definition of biovars (predicatedupon two biochemical assays) does not accurately reflect the phylogeneticrelationships within this species. Comparison of four virulent Y. pestisstrains with the human-avirulent strain 91001 provides further insightinto the genetic basis of virulence to humans.

  9. The Physical Internet and Business Model Innovation

    Directory of Open Access Journals (Sweden)

    Diane Poulin

    2012-06-01

    Full Text Available Building on the analogy of data packets within the Digital Internet, the Physical Internet is a concept that dramatically transforms how physical objects are designed, manufactured, and distributed. This approach is open, efficient, and sustainable beyond traditional proprietary logistical solutions, which are often plagued by inefficiencies. The Physical Internet redefines supply chain configurations, business models, and value-creation patterns. Firms are bound to be less dependent on operational scale and scope trade-offs because they will be in a position to offer novel hybrid products and services that would otherwise destroy value. Finally, logistical chains become flexible and reconfigurable in real time, thus becoming better in tune with firm strategic choices. This article focuses on the potential impact of the Physical Internet on business model innovation, both from the perspectives of Physical-Internet enabled and enabling business models.

  10. Humoral and cellular immune responses to Yersinia pestis Pla antigen in humans immunized with live plague vaccine.

    Science.gov (United States)

    Feodorova, Valentina A; Lyapina, Anna M; Khizhnyakova, Maria A; Zaitsev, Sergey S; Sayapina, Lidiya V; Arseneva, Tatiana E; Trukhachev, Alexey L; Lebedeva, Svetlana A; Telepnev, Maxim V; Ulianova, Onega V; Lyapina, Elena P; Ulyanov, Sergey S; Motin, Vladimir L

    2018-06-01

    To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis. PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting. The analysis of antibody response was complicated with a strong reactivity of Pla with normal human sera. The linear Pla B-cell epitopes were mapped using a library of 15-mer overlapping peptides. Twelve peptides that reacted specifically with sera of vaccinated donors were found together with a major cross-reacting peptide IPNISPDSFTVAAST located at the N-terminus. PBMCs were stimulated with recombinant Pla followed by proliferative analysis and cytokine profiling. The T-cell recall response was pronounced in vaccinees less than a year post-immunization, and became Th17-polarized over time after many rounds of vaccination. The Pla protein can serve as a biomarker of successful vaccination with LPV. The diagnostic use of Pla will require elimination of cross-reactive parts of the antigen.

  11. Tularemia, plague, yersiniosis, and Tyzzer’s disease in wild rodents and lagomorphs in Canada: A review

    Science.gov (United States)

    Wobeser, Gary; Campbell, G. Douglas; Dallaire, André; McBurney, Scott

    2009-01-01

    Information related to infection of wild rodents or lagomorphs in Canada by Francisella tularensis, Yersinia pestis, other Yersinia spp., and Clostridium piliforme was searched for this study. Reports on tularemia in humans linked to these species came from diagnostic databases, literature, wildlife health specialists, and public health agencies. Tularemia has been diagnosed in 8 species of wild rodent and 2 species in the genus Lepus in Canada. Tularemia occurred in wild animals, or in humans associated with these species, in all jurisdictions except the Yukon and Nunavut. Tularemia was diagnosed most frequently in beaver, muskrats, and snowshoe hares, and although tularemia is closely linked to cottontail rabbits in the USA, it has not been reported in cottontails in Canada. Tularemia in humans was associated with muskrats and hares more commonly than with beaver. Plague was diagnosed in bushy-tailed woodrats in British Columbia in 1988. Based on surveys, Y. pestis may occur enzootically in southern Alberta, Saskatchewan, and British Columbia. Infection with Yersinia pseudotuberculosis and Y. enterocolitica has been diagnosed in beaver, muskrats, and snowshoe hares in many provinces. Tyzzer’s disease has been diagnosed in muskrats in British Columbia, Saskatchewan, Ontario, and Quebec and in snowshoe hares in Ontario. Infection with these bacteria is likely much more frequent than indicated by diagnostic records. PMID:20190973

  12. The lagRST Model: A Turbulence Model for Non-Equilibrium Flows

    Science.gov (United States)

    Lillard, Randolph P.; Oliver, A. Brandon; Olsen, Michael E.; Blaisdell, Gregory A.; Lyrintzis, Anastasios S.

    2011-01-01

    This study presents a new class of turbulence model designed for wall bounded, high Reynolds number flows with separation. The model addresses deficiencies seen in the modeling of nonequilibrium turbulent flows. These flows generally have variable adverse pressure gradients which cause the turbulent quantities to react at a finite rate to changes in the mean flow quantities. This "lag" in the response of the turbulent quantities can t be modeled by most standard turbulence models, which are designed to model equilibrium turbulent boundary layers. The model presented uses a standard 2-equation model as the baseline for turbulent equilibrium calculations, but adds transport equations to account directly for non-equilibrium effects in the Reynolds Stress Tensor (RST) that are seen in large pressure gradients involving shock waves and separation. Comparisons are made to several standard turbulence modeling validation cases, including an incompressible boundary layer (both neutral and adverse pressure gradients), an incompressible mixing layer and a transonic bump flow. In addition, a hypersonic Shock Wave Turbulent Boundary Layer Interaction with separation is assessed along with a transonic capsule flow. Results show a substantial improvement over the baseline models for transonic separated flows. The results are mixed for the SWTBLI flows assessed. Separation predictions are not as good as the baseline models, but the over prediction of the peak heat flux downstream of the reattachment shock that plagues many models is reduced.

  13. Characterization of Yersinia pestis Interactions with Human Neutrophils In vitro

    Directory of Open Access Journals (Sweden)

    Sophia C. Dudte

    2017-08-01

    Full Text Available Yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. The bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. Neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and Y. pestis have been demonstrated in vivo. In contrast to macrophages, neutrophils have been considered non-permissive to Y. pestis intracellular survival. Several studies have shown killing of the vast majority of Y. pestis ingested by human neutrophils. However, survival of 10–15% of Y. pestis after phagocytosis by neutrophils is consistently observed. Furthermore, these surviving bacteria eventually replicate within and escape from the neutrophils. We set out to further characterize the interactions between Y. pestis and human neutrophils by (1 determining the effects of known Y. pestis virulence factors on bacterial survival after uptake by neutrophils, (2 examining the mechanisms employed by the neutrophil to kill the majority of intracellular Y. pestis, (3 determining the activation phenotype of Y. pestis-infected neutrophils, and (4 characterizing the Y. pestis-containing phagosome in neutrophils. We infected human neutrophils in vitro with Y. pestis and assayed bacterial survival and uptake. Deletion of the caf1 gene responsible for F1 capsule production resulted in significantly increased uptake of Y. pestis. Surprisingly, while the two-component regulator PhoPQ system is important for survival of Y. pestis within neutrophils, pre-induction of this system prior to infection did not increase bacterial survival. We used an IPTG-inducible mCherry construct to distinguish viable from non-viable intracellular bacteria and determined the association of the Y. pestis-containing phagosome with neutrophil NADPH-oxidase and markers of primary, secondary and tertiary granules. Additionally, we show that inhibition of

  14. Temporal variation in the prevalence of the crayfish plague pathogen, Aphanomyces astaci, in three Czech spiny-cheek crayfish populations

    Directory of Open Access Journals (Sweden)

    Matasová K.

    2011-06-01

    Full Text Available North American crayfish species are natural hosts of the crayfish plague pathogen Aphanomyces astaci. The spiny-cheek crayfish Orconectes limosus, widespread in Central Europe, is the main reservoir of A. astaci in Czech Republic. We tested if there are temporal changes in the prevalence of infected individuals (i.e., the proportion of individuals in which the pathogen is detected in spiny-cheek crayfish populations. Crayfish from three populations shown previously to be infected to different extents (high, intermediate and low, were repeatedly sampled in different years (2004–2010 and seasons. The presence of A. astaci in the soft abdominal crayfish cuticle was tested by specific amplification of the pathogen DNA. There was no substantial temporal variation in pathogen prevalence in the highly and very lowly infected populations. However, a significant long-term as well as seasonal decrease was found in the intermediately infected population. This decline could be related to a decrease in population density over the studied years, and to crayfish seasonal moulting, respectively. A reliable estimate of pathogen prevalence in American crayfish populations thus requires repeated monitoring over years, preferably during the same season before the main period of crayfish moulting.

  15. White plague disease outbreak in a coral reef at Los Roques National Park, Venezuela.

    Science.gov (United States)

    Croquer, Aldo; Pauls, Sheila M; Zubillaga, Ainhoa L

    2003-06-01

    Coral diseases have been reported as a major problem affecting Caribbean coral reefs. During August 2000, a coral mortality event of White Plague Disease-II (WPD-II) was observed at Madrizqui Reef in Los Roques National Park, Venezuela. This disease was identified as the major cause of coral mortality, affecting 24% of all colonies surveyed (n = 1 439). Other diseases such as Black Band Disease (BBD), Yellow Blotch Disease (YBD), Dark Spots Disease (DSD) and White Band Disease (WBD) were also recorded, but showed a lower incidence (0.14-0.97%). Two depth intervals, D1 (5.5-6.5 m) and D2 (9-9.5 m) were surveyed with two sets of three band transects 50 x 2 m long, placed parallel to the long axis of the reef. All healthy and injured corals, along each band transect, were counted and identified to species level. Additionally, all diseases and recent mortality that were still identifiable on each colony also were recorded. The incidence of colonies affected by WPD-II ranged from 12.8 to 33% among transects, where thirteen species of scleractinian corals showed several degrees of mortality. The species most affected were Montastraea annularis (39.13%), M. faveolata (26.67%), M. franksi (9.86%), Stephanocoenia intersepta (7.25%), Colpophyllia natans (6.96%), Diploria labyrinthiformis (2.99%), Mycetophyllia aliciae (2.03%), M. cavernosa (1.74%), and D. strigosa (1.45%). WPD-II was more common in the deeper strata (9-9.5 m), where 63% of the surveyed colonies were affected, although the disease was present along the entire reef. Presently, it is imperative to determine how fast the disease is spreading across the reef, how the disease spreads across the affected colonies and what the long-term effects on the reef will be.

  16. High-Speed Shaft Bearing Loads Testing and Modeling in the NREL Gearbox Reliability Collaborative: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    McNiff, B.; Guo, Y.; Keller, J.; Sethuraman, L.

    2014-12-01

    Bearing failures in the high speed output stage of the gearbox are plaguing the wind turbine industry. Accordingly, the National Renewable Energy Laboratory (NREL) Gearbox Reliability Collaborative (GRC) has performed an experimental and theoretical investigation of loads within these bearings. The purpose of this paper is to describe the instrumentation, calibrations, data post-processing and initial results from this testing and modeling effort. Measured HSS torque, bending, and bearing loads are related to model predictions. Of additional interest is examining if the shaft measurements can be simply related to bearing load measurements, eliminating the need for invasive modifications of the bearing races for such instrumentation.

  17. Proteolysis of plasminogen activator inhibitor-1 by Yersinia pestis remodulates the host environment to promote virulence.

    Science.gov (United States)

    Eddy, J L; Schroeder, J A; Zimbler, D L; Caulfield, A J; Lathem, W W

    2016-09-01

    Essentials Effect of plasminogen activator inhibitor (PAI)-1 on plague and its Y. pestis cleavage is unknown. An intranasal mouse model of infection was used to determine the role of PAI-1 in pneumonic plague. PAI-1 is cleaved and inactivated by the Pla protease of Y. pestis in the lung airspace. PAI-1 impacts both bacterial outgrowth and the immune response to respiratory Y. pestis infection. Click to hear Dr Bock discuss pathogen activators of plasminogen. Background The hemostatic regulator plasminogen activator inhibitor-1 (PAI-1) inactivates endogenous plasminogen activators and aids in the immune response to bacterial infection. Yersinia pestis, the causative agent of plague, produces the Pla protease, a virulence factor that is required during plague. However, the specific hemostatic proteins cleaved by Pla in vivo that contribute to pathogenesis have not yet been fully elucidated. Objectives To determine whether PAI-1 is cleaved by the Pla protease during pneumonic plague, and to define the impact of PAI-1 on Y. pestis respiratory infection in the presence or absence of Pla. Methods An intranasal mouse model of pneumonic plague was used to assess the levels of total and active PAI-1 in the lung airspace, and the impact of PAI-1 deficiency on bacterial pathogenesis, the host immune response and plasmin generation following infection with wild-type or ∆pla Y. pestis. Results We found that Y. pestis cleaves and inactivates PAI-1 in the lungs in a Pla-dependent manner. The loss of PAI-1 enhances Y. pestis outgrowth in the absence of Pla, and is associated with increased conversion of plasminogen to plasmin. Furthermore, we found that PAI-1 regulates immune cell recruitment, cytokine production and tissue permeability during pneumonic plague. Conclusions Our data demonstrate that PAI-1 is an in vivo target of the Pla protease in the lungs, and that PAI-1 is a key regulator of the pulmonary innate immune response. We conclude that the inactivation of PAI-1 by Y

  18. Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.

    Science.gov (United States)

    La Merrill, Michele A; Sethi, Sunjay; Benard, Ludovic; Moshier, Erin; Haraldsson, Borje; Buettner, Christoph

    2016-11-01

    Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. We hypothesized that perinatal DDT exposure causes hypertension in adult mice. DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure. Citation: La Merrill M, Sethi S, Benard L, Moshier E, Haraldsson B, Buettner C. 2016. Perinatal DDT exposure induces hypertension and cardiac hypertrophy in adult mice. Environ Health Perspect 124:1722-1727; http://dx.doi.org/10.1289/EHP164.

  19. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    International Nuclear Information System (INIS)

    Tully, Damien C.; Fares, Mario A.

    2008-01-01

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes

  20. Indoor environmental factors associated with pulmonary function among adults in an acid rain-plagued city in Southwest China.

    Science.gov (United States)

    Yu, Jie; Zhang, Longju; Luo, Ya; Tang, Yin; Tuo, Fangxu; Yang, Jiaqi; Xu, Jie

    2017-04-01

    To assess the association of indoor environmental risk factors with respiratory function among adults in an acid rain-plagued city in China where coal use is frequent. The subjects were randomly selected in the winter season. Information on selected home environmental factors was collected through administered questionnaires. Additionally, pulmonary function tests, including Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV 1 ), FEV 1 /FVC and Peak Expiratory Flow Rate (PEFR) were also performed in participants. This study showed that, among a variety of risk factors, coal fuel use, cooking oil fumes and active and passive smoking exposure together with asthma in childhood were important factors for deterioration of pulmonary function among adults in the winter season (p kitchen was located in the living room or bedroom, who opened their windows only occasionally or never, who noted the presence of cooking oil fumes and pests, whose bedroom was shared by 3 or more residents and who kept pets tended to exhibit lower values of FVC, FEV 1 and PEFR values compared with non-exposed counterparts (p < 0.05). This study demonstrated impaired pulmonary function among adults who were exposed to indoor risk factors, such as coal fires and cigarette smoking compared to non-users in the winter season and emphasizes the need for public health efforts to decrease exposure to indoor air pollution.