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Sample records for modern bubonic plague

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

    PubMed

    Newman, Kira L S

    2012-01-01

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

  2. Metapopulation dynamics of bubonic plague.

    PubMed

    Keeling, M J; Gilligan, C A

    2000-10-19

    Bubonic plague is widely regarded as a disease of mainly historical importance; however, with increasing reports of incidence and the discovery of antibiotic-resistant strains of the plague bacterium Yersinia pestis, it is re-emerging as a significant health concerns. Here we bypass the conventional human-disease models, and propose that bubonic plague is driven by the dynamics of the disease in the rat population. Using a stochastic, spatial metapopulation model, we show that bubonic plague can persist in relatively small rodent populations from which occasional human epidemics arise, without the need for external imports. This explains why historically the plague persisted despite long disease-free periods, and how the disease re-occurred in cities with tight quarantine control. In a contemporary setting, we show that human vaccination cannot eradicate the plague, and that culling of rats may prevent or exacerbate human epidemics, depending on the timing of the cull. The existence of plague reservoirs in wild rodent populations has important public-health implications for the transmission to urban rats and the subsequent risk of human outbreaks.

  3. The bubonic plague.

    PubMed

    McEvedy, C

    1988-02-01

    In A.D. 1346 some 100 million people inhabited Europe, northern Africa and the Near East. Five years later 25 million were dead--victims of the Black Death. The plague kept reappearing, but the epidemics did not spread as widely: apparently a new and milder strain of Yersinia pestis evolved that made at least some people immune to the virulent strain.

  4. Bubonic and pneumonic plague - Uganda, 2006.

    PubMed

    2009-07-24

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

  5. Vaccination against bubonic and pneumonic plague.

    PubMed

    Titball, R W; Williamson, E D

    2001-07-20

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

  6. A Deadly Path: Bacterial Spread During Bubonic Plague

    PubMed Central

    Gonzalez, Rodrigo J.; Miller, Virginia L.

    2016-01-01

    Yersinia pestis causes bubonic plague, a fulminant disease where host immune responses are abrogated. Recently developed in vivo models of plague have resulted in new ideas regarding bacterial spread in the body. Deciphering bacterial spread is key to understanding Y. pestis and the immune responses it encounters during infection. PMID:26875618

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

    PubMed

    Gonzalez, Rodrigo J; Miller, Virginia L

    2016-04-01

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

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

    PubMed

    McMichael, Anthony J

    2010-08-27

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

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

    PubMed

    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.

  10. Solar Variability and the Decline of the Bubonic Plague

    NASA Astrophysics Data System (ADS)

    2001-10-01

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

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

    PubMed

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

    2007-09-01

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

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

    USGS Publications Warehouse

    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

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

    PubMed

    Yu, Hwa-Lung; Christakos, George

    2006-03-17

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

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

    PubMed Central

    Yu, Hwa-Lung; Christakos, George

    2006-01-01

    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 patterns of different diseases

  15. Puerto Cabello and the Bubonic Plague epidemic (1903-1908).

    PubMed

    Merida, M T

    1999-12-01

    Epidemics have a social-economic character which affect certain historic periods. The Bubonic Plague, known as the Black Death, in the Middle Ages, caused the deaths of a quarter of Europe's population. The last plague epidemic originated in China, in the year 1893, and then spread to Europe at the end of the century. The French port of Marseille, in 1903, was the open door to the American Continent, the plague being detected in Panama in 1905 and officially recognised by Cipriano Castro's Government in 1908. The Venezuelan epidemic occurred during the Liberal Restoration Period. It was met by the Sanitary Authorities with a vision of 'medical positivism'. In our present research, we analyze the importance of Puerto Cabello, together with La Guaira and Cumana, the ports of arrival for the major quanity of European imports by steamships during 1903-1908. The sanitary strategy of medical health advisors and the nonfulfilment of proposed rules within the framework of the crisis of the Venezuelan Liberalism allowed the illness to enter and spread.

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

    PubMed

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

    2004-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

  19. Kinetics of Disease Progression and Host Response in a Rat Model of Bubonic Plague

    PubMed Central

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

    2005-01-01

    Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease. PMID:15855643

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

    PubMed

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

    2005-05-01

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

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

    PubMed

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

    2002-03-01

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

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

    PubMed

    Alvarez, M Lucrecia; Cardineau, Guy A

    2010-01-01

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

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

    PubMed Central

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

    2002-01-01

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

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

    PubMed Central

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

    2015-01-01

    Background 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. Methodology/Principal Findings 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. Significance 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

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

    PubMed

    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

  6. Plague

    MedlinePlus

    ... Bubonic plague causes the tonsils, adenoids, spleen, and thymus to become inflamed. Symptoms include fever, aches, chills, and tender lymph glands. In septicemic plague, bacteria multiply in the blood. ...

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

    PubMed

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

    2010-12-01

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

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

    PubMed

    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.

  9. New Insights into How Yersinia pestis Adapts to Its Mammalian Host during Bubonic Plague

    PubMed Central

    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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    2006-08-01

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

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

    PubMed

    López Piñero, José María

    2006-01-01

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

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

    PubMed

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

    2017-06-01

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

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

    PubMed Central

    Whittles, Lilith K.; Hall, Ian

    2017-01-01

    Bubonic plague has caused three deadly pandemics in human history: from the mid-sixth to mid-eighth century, from the mid-fourteenth to the mid-eighteenth century and from the end of the nineteenth until the mid-twentieth century. Between the second and the third pandemics, plague was causing sporadic outbreaks in only a few countries in the Middle East, including Egypt. Little is known about this historical phase of plague, even though it represents the temporal, geographical and phylogenetic transition between the second and third pandemics. Here we analysed in detail an outbreak of plague that took place in Cairo in 1801, and for which epidemiological data are uniquely available thanks to the presence of medical officers accompanying the Napoleonic expedition into Egypt at that time. We propose a new stochastic model describing how bubonic plague outbreaks unfold in both rat and human populations, and perform Bayesian inference under this model using a particle Markov chain Monte Carlo. Rat carcasses were estimated to be infectious for approximately 4 days after death, which is in good agreement with local observations on the survival of infectious rat fleas. The estimated transmission rate between rats implies a basic reproduction number R0 of approximately 3, causing the collapse of the rat population in approximately 100 days. Simultaneously, the force of infection exerted by each infected rat carcass onto the human population increases progressively by more than an order of magnitude. We also considered human-to-human transmission via pneumonic plague or human specific vectors, but found this route to account for only a small fraction of cases and to be significantly below the threshold required to sustain an outbreak. PMID:28637916

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

    PubMed

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

    2008-02-01

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

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2003-01-18

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

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

    PubMed

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

    2004-04-01

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

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

    PubMed

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

    2008-09-06

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

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

    PubMed

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

    2009-06-16

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

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

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2011-12-01

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

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

    PubMed

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

    2006-04-04

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

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

    PubMed Central

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

    2006-01-01

    Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread. PMID:16567636

  6. Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model

    PubMed Central

    Xiao, Xiaodong; Zhu, Zhongyu; Dankmeyer, Jennifer L.; Wormald, Michael M.; Fast, Randy L.; Worsham, Patricia L.; Cote, Christopher K.; Amemiya, Kei; Dimitrov, Dimiter S.

    2010-01-01

    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. PMID:20976274

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

    PubMed

    Xiao, Xiaodong; Zhu, Zhongyu; Dankmeyer, Jennifer L; Wormald, Michael M; Fast, Randy L; Worsham, Patricia L; Cote, Christopher K; Amemiya, Kei; Dimitrov, Dimiter S

    2010-10-13

    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.

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

    PubMed

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

    2008-08-01

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

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

    PubMed

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

    2006-08-01

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

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

    PubMed Central

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

    2006-01-01

    Yersinia pestis causes bubonic plague, characterized by an enlarged, painful lymph node, termed a bubo, that develops after bacterial dissemination from a fleabite site. In susceptible animals, the bacteria rapidly escape containment in the lymph node, spread systemically through the blood, and produce fatal sepsis. The fulminant progression of disease has been largely ascribed to the ability of Y. pestis to avoid phagocytosis and exposure to antimicrobial effectors of innate immunity. In vivo microarray analysis of Y. pestis gene expression, however, revealed an adaptive response to nitric oxide (NO)-derived reactive nitrogen species and to iron limitation in the extracellular environment of the bubo. Polymorphonuclear neutrophils recruited to the infected lymph node expressed abundant inducible NO synthase, and several Y. pestis homologs of genes involved in the protective response to reactive nitrogen species were up-regulated in the bubo. Mutation of one of these genes, which encodes the Hmp flavohemoglobin that detoxifies NO, attenuated virulence. Thus, the ability of Y. pestis to destroy immune cells and remain extracellular in the bubo appears to limit exposure to some but not all innate immune effectors. High NO levels induced during plague may also influence the developing adaptive immune response and contribute to septic shock. PMID:16864791

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

    PubMed

    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

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

    PubMed

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

    2006-09-05

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

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

    PubMed

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

    2012-01-01

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

  14. The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

    PubMed Central

    Fetherston, Jacqueline D.; Mier, Ildefonso; Truszczynska, Helena

    2012-01-01

    The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, iron-limiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD50) relative to the Yfe+ Feo+ parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified. PMID:22927049

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2011-02-01

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

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

    PubMed

    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.

  18. Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:24225642

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

    PubMed

    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.

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

    PubMed

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

    2010-07-01

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

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

    PubMed

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

    2011-09-16

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

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

  7. Plague: Clinics, Diagnosis and Treatment.

    PubMed

    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.

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

    PubMed

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

    2009-04-06

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2006-03-24

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

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

    PubMed

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

    2007-01-15

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

  12. Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague.

    PubMed

    Powell, Bradford S; Andrews, Gerard P; Enama, Jeffrey T; Jendrek, Scott; Bolt, Chris; Worsham, Patricia; Pullen, Jeffrey K; Ribot, Wilson; Hines, Harry; Smith, Leonard; Heath, David G; Adamovicz, Jeffrey J

    2005-01-01

    A two-component recombinant fusion protein antigen was re-engineered and tested as a medical counter measure against the possible biological threat of aerosolized Yersinia pestis. The active component of the proposed subunit vaccine combines the F1 capsular protein and V virulence antigen of Y. pestis and improves upon the design of an earlier histidine-tagged fusion protein. In the current study, different production strains were screened for suitable expression and a purification process was optimized to isolate an F1-V fusion protein absent extraneous coding sequences. Soluble F1-V protein was isolated to 99% purity by sequential liquid chromatography including capture and refolding of urea-denatured protein via anion exchange, followed by hydrophobic interaction, concentration, and then transfer into buffered saline for direct use after frozen storage. Protein identity and primary structure were verified by mass spectrometry and Edman sequencing, confirming a purified product of 477 amino acids and removal of the N-terminal methionine. Purity, quality, and higher-order structure were compared between lots using RP-HPLC, intrinsic fluorescence, CD spectroscopy, and multi-angle light scattering spectroscopy, all of which indicated a consistent and properly folded product. As formulated with aluminum hydroxide adjuvant and administered in a single subcutaneous dose, this new F1-V protein also protected mice from wild-type and non-encapsulated Y. pestis challenge strains, modeling prophylaxis against pneumonic and bubonic plague. These findings confirm that the fusion protein architecture provides superior protection over the former licensed product, establish a foundation from which to create a robust production process, and set forth assays for the development of F1-V as the active pharmaceutical ingredient of the next plague vaccine.

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

    PubMed

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

    2008-04-01

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

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed

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

    2005-07-01

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

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

    PubMed

    Monecke, Stefan; Monecke, Hannelore; Monecke, Jochen

    2009-12-01

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

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

    PubMed

    Bland, David M; Anderson, Deborah M

    2013-11-05

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

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

    PubMed

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

    2006-05-15

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

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

    PubMed

    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.

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

    PubMed

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

    2008-03-20

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

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

    PubMed

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

    2017-06-21

    A number of bacterial pathogens require the ZnuABC Zinc (Zn(2+)) transporter and/or a second Zn(2+) transport system to overcome Zn(2+) sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn(2+) transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn(2+) transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic plague while a ybtX mutant retains high virulence in both plague models. While sequestration of host Zn is a key nutritional immunity factor, excess Zn appears to have a significant antimicrobial role in controlling intracellular bacterial survival. Here, we demonstrate that ZntA, a Zn(2+) exporter, plays a role in resistance to Zn toxicity in vitro, but that a zntA zur double mutant retains high virulence in both pneumonic and bubonic plague models and survival in macrophages. We also confirm that Ybt does not directly bind Zn(2+)in vitro under the conditions tested. However, we detect a significant increase in Zn(2+)-binding ability of filtered supernatants from a Ybt(+) strain compared to those from a strain unable to produce the siderophore, supporting our previously published data that Ybt biosynthetic genes are involved in the production of a secreted Zn-binding molecule (zincophore). Our data suggest that Ybt or a modified Ybt participate in or promote Zn-binding activity in culture supernatants and is involved in Zn acquisition in Y. pestis.

  4. Validation of Inverse Seasonal Peak Mortality in Medieval Plagues, Including the Black Death, in Comparison to Modern Yersinia pestis-Variant Diseases

    PubMed Central

    Welford, Mark R.; Bossak, Brian H.

    2009-01-01

    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. PMID:20027294

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

    PubMed

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

    2009-03-01

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

  6. Plague studies*

    PubMed Central

    Pollitzer, R.

    1953-01-01

    Epidemiological aspects of (a) bubonic plague and (b) primary pneumonic plague are discussed separately in this study. The cause, spread, and persistence of bubonic outbreaks are dealt with. In the case of primary pneumonic plague, the author systematically reviews the factors influencing the spread of the disease: climatic and social conditions, infectivity of the patients, immunity, and control measures. In discussing the cause of pneumonic plague outbreaks, the author deals with the possible influence of a special virulence of pneumonic strains, the role of the rodent and flea species involved, and the possibility of a pneumotropismus acquired by Pasteurella pestis. The periodicity (cyclical and secular) of bubonic plague epidemics is discussed with a view to the possible forecasting of future epidemics. The author indicates the influence of race, age, sex, and occupation on the incidence of both forms of the disease. PMID:13082391

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-05-24

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

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

    PubMed

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

    2006-09-01

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

  10. [Pulmonic plague].

    PubMed

    Hovette, P; Burgel, P R; Camara, P; Sane, M; Auregan, G; Klotz, F

    1998-12-01

    One hundred years after Yersin discovered Yersinia pestis during the plague epidemic in Hong Kong in 1894, human plague still has not been eliminated. The epidemic in 1994 in India, a country where no cases had been observed since 1996, raised great concern. Plague is an epizootic bacterial infection caused by a Gram negative coccobacillus, Y. pestis, transmitted by the bite of infected fleas. Bubonic plague is the most common form. Other clinical presentations include asymptomatic plague, abortive plague, pharyngeal plague, septicemic plague, meningeal plague, and primary or secondary pneumonic plague which is observed in 5 to 20% of cases. Plague is a highly communicable disease between humans despite antibiotic therapy which has reduced mortality by 80%. The prognosis depends on early diagnosis. Streptomycin and cyclines are the gold standard treatment.

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

    PubMed

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

    2011-05-01

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

  12. Plague studies*

    PubMed Central

    Pollitzer, R.

    1953-01-01

    The author examines in detail the symptomatology, diagnosis, and treatment of plague, and outlines the problem of the length of the incubation period. The clinical features commonly met with in all severely-affected plague patients, regardless of the primary localization of the infection, are described. The author then deals with the symptomatology and manifestations of bubonic plague as compared to those of primary pneumonic plague. The importance of a clinical diagnosis, from the point of view of prevention, is stressed, and the differential diagnosis of various forms of the disease is described. The study contains a detailed discussion of the respective merits of antibiotic treatment, serotherapy, and sulfonamide treatment. The author points out that the outstanding success of streptomycin and some other antibiotics will probably relegate the sulfonamides to the second rank in the treatment of bubonic plague. PMID:13082390

  13. Protective Efficacy of Recombinant Yersinia Outer Proteins against Bubonic Plague Caused by Encapsulated and Nonencapsulated Yersinia pestis

    PubMed Central

    Andrews, G. P.; Strachan, S. T.; Benner, G. E.; Sample, A. K.; Anderson, G. W.; Adamovicz, J. J.; Welkos, S. L.; Pullen, J. K.; Friedlander, A. M.

    1999-01-01

    To evaluate the role of Yersinia outer proteins (Yops) in conferring protective immunity against plague, six yop loci from Yersinia pestis were individually amplified by PCR, cloned, and expressed in Escherichia coli. The recombinant proteins were purified and injected into mice. Most Yop-vaccinated animals succumbed to infection with either wild-type encapsulated Y. pestis or a virulent, nonencapsulated isogenic variant. Vaccination with YpkA significantly prolonged mean survival time but did not increase overall survival of mice infected with the nonencapsulated strain. The only significant protection against death was observed in YopD-vaccinated mice challenged with the nonencapsulated strain. PMID:10024607

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

    PubMed

    Hawgood, Barbara J

    2007-02-01

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

  15. Plague

    MedlinePlus

    ... U.S. Department of Defense, the Centers for Disease Control and Prevention, and the U.S. Department of Energy to develop promising antibiotics and intervention strategies to treat and prevent plague infection. Featured Research ...

  16. Plague

    MedlinePlus

    ... Tests Tests that may be done include: Blood culture Culture of lymph node aspirate (fluid taken from an affected lymph node or bubo) Sputum culture Treatment People with the plague need immediate treatment. ...

  17. 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

    NASA Astrophysics Data System (ADS)

    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

  18. Plague

    USGS Publications Warehouse

    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.

  19. Plague studies*

    PubMed Central

    Pollitzer, R.

    1953-01-01

    In examining the control and prevention of plague, the author pays particular attention to the control of commensal rodents and their fleas. The various rat poisons in current use, their efficacy and practical application, and the dangers involved in their manipulation are described in great detail. The author also discusses other anti-rodent measures such as fumigation, rat-proofing, sanitation, protection of food, etc. The second part of the study deals with: vector control—the outstanding value of DDT application in rodent-flea control is emphasized—, the direct control of bubonic and pneumonic plague, and the control of the spread of plague at a distance. PMID:20603968

  20. [Historical and biological approaches to the study of Modern Age French plague mass burials].

    PubMed

    Bianuccii, Raffaella; Tzortzis, Stéfan; Fornaciari, Gino; Signoli, Michel

    2010-01-01

    The "Black Death" and subsequent epidemics from 1346 to the early 18th century spread from the Caspian Sea all over Europe six hundred years after the outbreak of the Justinian plague (541-767 AD). Plague has been one of the most devastating infectious diseases that affected the humankind and has caused approximately 200 million human deaths historically. Here we describe the different approaches adopted in the study of several French putative plague mass burials dating to the Modern Age (16th-18th centuries). Through complementation of historical, archaeological and paleobiological data, ample knowledge of both the causes that favoured the spread of the Medieval plague in cities, towns and small villages and of the modification of the customary funerary practices in urban and rural areas due to plague are gained.

  1. The cause of the plague of Athens: plague, typhoid, typhus, smallpox, or measles?

    PubMed

    Cunha, Burke A

    2004-03-01

    The plague of Athens raged for 4 years and resulted in the defeat of Athens. The cause of the plague of Athens continues to be debated. Infectious diseases most often cited as causes of the plague include influenza, epidemic typhus, typhoid fever, bubonic plague, smallpox, and measles. Thucydides provides the only available description of the plague of Athens. Given the nuances of the translation, bubonic plague, smallpox, and measles are the most likely causes of the plague. In my view, measles is the most likely cause of the plague of Athens.

  2. Plague: from natural disease to bioterrorism

    PubMed Central

    2005-01-01

    Yersinia pestis is the causative agent of plague, an enzootic vectorborne disease usually infecting rodents (rats) and fleas. Humans can become infected after being bitten by fleas that have fed on infected rodents. In humans, the disease usually occurs in the form of bubonic plague. In rare cases, the infection spreads to the lungs via the bloodstream and causes secondary pneumonic plague. Person-to-person transmission has been described for pneumonic plague but is rare in primary bubonic plague. Bubonic plague can usually be treated successfully with antibiotics; however, pneumonic plague develops rapidly and carries a high fatality rate despite immediate treatment with antibiotics. Plague is also recognized as a potential agent of bioterrorism. It has been used, or considered for use, as a biologic weapon on several occasions. It is important for the medical community to be familiar with the epidemiology, diagnosis, and symptoms of plague so it can deliver an appropriate and calm response should the unthinkable happen. PMID:16200159

  3. Two medieval plague treatises and their afterlife in early modern England.

    PubMed

    Keiser, George R

    2003-07-01

    This study of an adaptation of the popular John of Burgundy plague treatise by Thomas Moulton, a Dominican friar, ca. 1475, and a translation of the so-called Canutus plague treatise by Thomas Paynell, printed 1534, shows how the medieval traditions they represent were carried forward, well into the sixteenth century, and also subjected to change in light of religious, moral, and medical concerns of early modern England. The former had a long life in print, ca. 1530-1580, whereas Paynell's translation exists in one printed version. Moulton's adaptation differs from its original and from the Canutus treatise in putting great emphasis on the idea that onsets of plague were acts of divine retribution for human sinfulness. In this respect, Moulton reshaped the tradition of the medieval plague treatise and anticipated the religious and social construction of plague that would take shape in the first half of the sixteenth century. Its long history in print indicates that Moulton's treatise expressed the spirit of that construction and probably influenced the construction as well. The contrasting histories of the two treatises attest not only to the dramatic change brought about by religious and social forces in the sixteenth century, but to a growing recognition of the value of the printing press for disseminating medical information-in forms that served social and ideological ends.

  4. Plague's partners in crime.

    PubMed

    Davis, Kimberly M; Isberg, Ralph R

    2014-09-18

    The hallmark of bubonic plague is the presence of grotesquely swollen lymph nodes, called buboes. This frenzied inflammatory response to Yersinia pestis is poorly understood. In this issue of Immunity, St. John et al. (2014) explore the mechanism by which Y. pestis spreads and thus leads to this striking lymphadenopathy.

  5. Yersinia outer proteins (YOPS) E, K and N are antigenic but non-protective compared to V antigen, in a murine model of bubonic plague.

    PubMed

    Leary, S E; Griffin, K F; Galyov, E E; Hewer, J; Williamson, E D; Holmström, A; Forsberg, A; Titball, R W

    1999-03-01

    The pathogenic Yersiniae produce a range of virulence proteins, encoded by a 70 kb plasmid, which are essential for infection, and also form part of a contact-dependent virulence mechanism. One of these proteins, V antigen, has been shown to confer a high level of protection against parenteral infection with Y. pestis in murine models, and is considered to be a protective antigen. In this study, the protective efficacy of V antigen has been compared in the same model with that of other proteins (YopE, YopK and YopN), which are part of the contact-dependent virulence mechanism. Mice immunised with two intraperitoneal doses of V antigen or each of the Yops, administered with either Alhydrogel or interleukin-12, produced high antigen-specific serum IgG titres. As shown in previous studies, V+Alhydrogel was fully protective, and 5/5 mice survived a subcutaneous challenge with 90 or 9x10(3) LD50's of Y. pestis GB. In addition, these preliminary studies also showed that V+IL-12 was partially protective: 4/5 or 3/5 mice survived a challenge with 90 or 9x10(3) LD50's, respectively. In contrast, none of the mice immunised with the Yops survived the challenges, and there was no significant delay in the mean time to death compared to mice receiving a control protein. These results show that using two different vaccine regimens, Yops E, K and N, failed to elicit protective immune responses in a murine model of plague, whereas under the same conditions, V antigen was fully or partially protective. Copyright 1999 Academic Press.

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

    PubMed

    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.

  7. Plague pneumonia disease caused by Yersinia pestis.

    PubMed

    Cleri, D J; Vernaleo, J R; Lombardi, L J; Rabbat, M S; Mathew, A; Marton, R; Reyelt, M C

    1997-03-01

    Plague is a zoonotic infection caused by Yersina pesits, a pleomorphic, gram-negative non-spore-forming coccobacillus that is more accurately classified as a subspecies of Y pseudotuberculosis. Animal reservoirs include rodents, rabbits, and occasionally larger animals. Cats become ill and have spread pneumonic disease to man. Dogs may be a significant sentinel animal as well as a reservoir, although do not usually become ill. Flea bites commonly spread disease to man. Person to person spread has not been a recent feature until the purported outbreak of plague and plague pneumonia in India in 1994. Other factors that increase risk of infection in endemic areas are occupation-veterinarians and assistants, pet ownership, direct animal-reservoir contact especially during the hunting season, living in households with an index case, and, mild winters, cool moist springs, and early summers. Clinical presentations include subclinical plague (positive serology without disease); plague pharyngitis; pestis minor (abortive bubonic plague); bubonic plague; septicemic plague; pneumonic plague; and plague meningitis. Most prominent of plague's differential diagnosis are Reye's syndrome, other causes of lymphadenitis, bacterial pneumonias, tularemia, and acute surgical abdomen. Treatment has reduced mortality from 40-90% to 5-18%. The drug of choice (except for plague meningitis) is streptomycin, with tetracyclines being alternatives. Parenteral cholamphenicol is the treatment of choice for plague meningitis. A tetracycline should be administered as chemoprophylaxis to all contacts over the age of 8 years. Plague vaccine is available, but is only partially protective.

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

    PubMed

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

    2012-06-01

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

  9. Clinical and epidemiological observations on an outbreak of plague in Nepal*

    PubMed Central

    Laforce, F. Marc; Acharya, I. L.; Stott, Gordon; Brachman, Philip S.; Kaufman, Arnold F.; Clapp, Richard F.; Shah, N. K.

    1971-01-01

    In the autumn of 1967, plague broke out among hill people in western Nepal, a country that had not previously reported human plague. Two persons were infected from an active sylvatic focus at a grazing area 5 km from Nawra, the village where the epidemic occurred. The second patient introduced plague into the village where the rest of the cases occurred. Clinical and epidemiological evidence suggests that plague was spread both by the airborne route, resulting in 6 cases of tonsillar plague and 1 case of primary pneumonic plague, as well as by infected fleas, resulting in 17 cases of bubonic plague. Since no evidence of a rodent epizootic was uncovered in the village itself, and because of the distinct clustering of the bubonic cases, human-to-human spread of plague by infected ectoparasite vectors, presumably Pulex irritans, is thought to have occurred. This focus probably represents the most southerly boundary of the central Asian plague area yet identified. PMID:5317008

  10. Predictive thresholds for plague in Kazakhstan.

    PubMed

    Davis, Stephen; Begon, Mike; De Bruyn, Luc; Ageyev, Vladimir S; Klassovskiy, Nikolay L; Pole, Sergey B; Viljugrein, Hildegunn; Stenseth, Nils Chr; Leirs, Herwig

    2004-04-30

    In Kazakhstan and elsewhere in central Asia, the bacterium Yersinia pestis circulates in natural populations of gerbils, which are the source of human cases of bubonic plague. Our analysis of field data collected between 1955 and 1996 shows that plague invades, fades out, and reinvades in response to fluctuations in the abundance of its main reservoir host, the great gerbil (Rhombomys opimus). This is a rare empirical example of the two types of abundance thresholds for infectious disease-invasion and persistence- operating in a single wildlife population. We parameterized predictive models that should reduce the costs of plague surveillance in central Asia and thereby encourage its continuance.

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

    PubMed Central

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

    2010-01-01

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

  12. Plague dynamics are driven by climate variation.

    PubMed

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

    2006-08-29

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

  13. Human plague in 1992.

    PubMed

    1994-01-14

    Trends in the incidence of human plague cases reported to the World Health Organization were provided for 1992 and between 1978 and 1992 by country. Not all countries report or record plague. In 1992, there were 9 countries reporting a total of 1582 cases, of which 138 were deaths. In 1991, there were 10 countries reporting a total of 1966 cases, of which 133 were deaths. The case fatality rate in 1992 was 8.7% and 10.4% averaged over the previous 10 years. Between 1978 and 1992, 14,856 cases of plague were reported, of which 1451 cases were fatal. Countries reporting totaled 21, but only 6 reported almost annually: Brazil, Madagascar, Myanmar, the United Republic of Tanzania, the USA, and Viet Nam. Peak numbers of cases occurred in 1984, 1988, and 1990-92. Africa totaled 61% of cases and 77% of deaths. In 1992, Madagascar and Zaire reported 412 cases, of which 102 were fatal. Plague in Madagascar was concentrated in the provinces of Antananarivo, Fianarantsoa, Mahajanga, and Toamasina. Most of the cases in 1991 were from Antananarivo Province (61 cases and 19 deaths) and Fianarantsoa Province (99 case and 5 deaths). Plague peaks occurred in January through May and November and December. Zaire deaths were concentrated in Upper Zaire in 5 rural Heath Zones: Logo (125 cases and 47 deaths), Rethy (54 cases and 4 deaths), Nyarembe (22 cases and 9 deaths), Rimba (11 cases and 4 deaths), and Bunia (2 cases and 1 death). Almost 60% of all deaths occurred during May to July and included bubonic, septicemic, and pulmonary plague. American plague cases totaled 158 and 6 deaths (Peru, Brazil, and the USA). Asia reported 1012 cases and 26 cases (China, Mongolia, Myanmar, and Viet Nam). In the USA, the 13 cases were recorded as 1 each in Frenso County, California; Owyhee County, Idaho; Douglas County, Nevada; Utah County, Utah; and Sheridan County, Wyoming; 2 in New Mexico (Santa Fe, and Albuquerque and San Miguel Counties); and Arizona (3 in Apache County and 1 in Pima County

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

    PubMed

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

    2010-12-17

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

  15. Role of the Yersinia pestis Yersiniabactin Iron Acquisition System in the Incidence of Flea-Borne Plague

    PubMed Central

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

    2010-01-01

    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. PMID:21179420

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

    PubMed

    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.

  17. Plague Symptoms

    MedlinePlus

    ... 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 ...

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

    PubMed

    Sabbatani, Sergio; Manfredi, Roberto; Fiorino, Sirio

    2012-06-01

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

  19. Plague: history and contemporary analysis.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  1. The plague under Commodus as an unintended consequence of Roman grain market regulation.

    PubMed

    Silver, Morris

    2012-01-01

    This paper begins with a review of Roman grain market policies. It is argued that policies such as forced sales and maximum prices made urban consumers hesitant to rely on the market for secure access to grain. Consequently, consumers hoarded grain in their homes. The hoarded grain formed a volatile fuel ready to be ignited by the arrival of the bubonic plague bacillus. This scenario fits events in the city of Rome under Commodus. Attested grain market interventions were followed by a severe epidemic, arguably bubonic plague, which decimated the city's population.

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

    PubMed

    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.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2009-02-01

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

  5. Plague vaccines and the molecular basis of immunity against Yersinia pestis.

    PubMed

    Quenee, Lauriane E; Schneewind, Olaf

    2009-12-01

    Yersinia pestis is the causative agent of bubonic and pneumonic plague, human diseases with high mortality. Due to the microbe's ability to spread rapidly, plague epidemics present a serious public health threat. A search for prophylactic measures was initially based on historical reports of bubonic plague survivors and their apparent immunity. Due to safety and efficacy concerns, killed whole-cell preparations or live-attenuated plague vaccines are no longer considered in the United States. Vaccine developers have focused on specific subunits of plague bacteria. LcrV, a protein at the tip of type III secretion needles, and F1, the capsular pilus antigen, are both recognized as plague protective antigens. Antibodies against LcrV and F1 interfere with Y. pestis type III injection of host cells. While LcrV is absolutely essential for Y. pestis virulence, expression of F1 is dispensable for plague pathogenesis in small animals, non-human primates and presumably also in humans. Several subunit vaccines, for example rF1+rV (rYP002), rF1V or rV10, are being developed to generate plague protection in humans. Efficacy testing and licensure for human use requires the establishment of correlates for plague immunity.

  6. Plague Prevention

    MedlinePlus

    ... visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics Info for ... soon as possible. Do not allow dogs or cats that roam free in endemic areas to sleep ...

  7. Plague Factsheet

    MedlinePlus

    ... southwestern states. For the Pacific states, the California ground squirrel and its fleas are the most common source. ... instance, prairie dogs, wood rats, chipmunks, and other ground squirrels and their fleas, suffer plague outbreaks and some ...

  8. Plague mortality and demographic depression in later medieval England.

    PubMed

    Poos, L R

    1981-01-01

    Both direct and indirect evidence implies that England experienced a lengthy period of stagnant or declining population during the later fourteenth and fifteenth centuries. The Black Death of 1348-1349 had brought about profound changes in England's agrarian economy, and this subsequent demographic depression is most commonly interpreted by historians as the result of plague mortality, recurring in severe outbreaks after the disease's introduction into the country. This paper reviews the evidence and assumptions behind this interpretation, in light of recent research by historical demographers and epidemiologists into bubonic plague epidemics and general mortality crises during the post-medieval period.

  9. Plague mortality and demographic depression in later medieval England.

    PubMed Central

    Poos, L. R.

    1981-01-01

    Both direct and indirect evidence implies that England experienced a lengthy period of stagnant or declining population during the later fourteenth and fifteenth centuries. The Black Death of 1348-1349 had brought about profound changes in England's agrarian economy, and this subsequent demographic depression is most commonly interpreted by historians as the result of plague mortality, recurring in severe outbreaks after the disease's introduction into the country. This paper reviews the evidence and assumptions behind this interpretation, in light of recent research by historical demographers and epidemiologists into bubonic plague epidemics and general mortality crises during the post-medieval period. PMID:7027638

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

    PubMed

    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

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

    PubMed

    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.

  12. Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model

    DTIC Science & Technology

    2010-10-01

    Institute of Allergy and Infectious Diseases Biodefense Program to Dimiter S. Dimitrov and agency Joint Science and Technology Office Defense Threat...antigens were coated to a Costar high binding 96-well plate ( Corning , Corning , NY) and incubated overnight at 4uC. The next day, the plate was blocked with 2

  13. Dynamics of the plague-wildlife-human system in Central Asia are controlled by two epidemiological thresholds.

    PubMed

    Samia, Noelle I; Kausrud, Kyrre Linné; Heesterbeek, Hans; Ageyev, Vladimir; Begon, Mike; Chan, Kung-Sik; Stenseth, Nils C

    2011-08-30

    Plague (caused by the bacterium Yersinia pestis) is a zoonotic reemerging infectious disease with reservoirs in rodent populations worldwide. Using one-half of a century of unique data (1949-1995) from Kazakhstan on plague dynamics, including data on the main rodent host reservoir (great gerbil), main vector (flea), human cases, and external (climate) conditions, we analyze the full ecoepidemiological (bubonic) plague system. We show that two epidemiological threshold quantities play key roles: one threshold relating to the dynamics in the host reservoir, and the second threshold relating to the spillover of the plague bacteria into the human population.

  14. Developing live vaccines against plague.

    PubMed

    Sun, Wei; Roland, Kenneth L; Curtiss, Roy

    2011-09-14

    Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom.  However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague.  This vaccine has not gained general acceptance because of safety concerns.  In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment.  In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plagu.

  15. Plague Vaccines: Status and Future.

    PubMed

    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.

  16. [Tholozan and plague in Persia].

    PubMed

    Mollaret, H H

    1998-09-01

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

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

    PubMed

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

    2011-04-01

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

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

    PubMed Central

    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

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

    PubMed

    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.

  20. Plague Reappearance in Algeria after 50 Years, 2003

    PubMed Central

    Bekhoucha, Souad; Chougrani, Saada; Razik, Fathia; Duchemin, Jean B.; Houti, Leila; Deharib, Larbi; Fayolle, Corinne; Makrerougrass, Banaouda; Dali-Yahia, Radia; Bellal, Ramdan; Belhabri, Leila; Chaieb, Amina; Tikhomirov, Evgueni; Carniel, Elisabeth

    2007-01-01

    An outbreak of plague occurred in the region of Oran, Algeria, from June to July 2003. Algeria had not reported this disease for >50 years. Eighteen bubonic cases were identified, and Yersinia pestis was isolated from 6 patients. Except for the index case-patient, all patients recovered. Targeted chemoprophylaxis, sanitation, and vector control played a crucial role in controlling the outbreak. Epidemiologic and biomolecular findings strongly suggested the existence of a local animal reservoir during this period, but its origin (resurgence or re-importation) could not be determined. This sudden and unexpected reemergence of plague, close to an important commercial seaport, is a textbook illustration of a public health event of international importance. It also demonstrates that the danger of plague reoccurrence is not limited to the currently indexed natural foci. PMID:18257987

  1. [A molecular basis of the plague vaccine development].

    PubMed

    Dentovskaia, S V; Kopylov, P Kh; Ivanov, S A; Ageev, S A; Anisimov, A P

    2013-01-01

    Molecular mechanisms of the Yersinia pestis pathogenicity and peculiarities of maturation of specific immunity to plague are reviewed. The history and modern state of the plague vaccine development are described. Special attention is focused on the prospects in the area of the plague vaccine development. The possible approaches to improvement of vaccine preparations are discussed.

  2. Yersinia pestis caf1 Variants and the Limits of Plague Vaccine Protection▿

    PubMed Central

    Quenee, Lauriane E.; Cornelius, Claire A.; Ciletti, Nancy A.; Elli, Derek; Schneewind, Olaf

    2008-01-01

    Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains. PMID:18347051

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

    PubMed

    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.

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

    PubMed

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

    2007-08-22

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

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

    PubMed

    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.

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

    PubMed

    do Nascimento, Dilene Raimundo

    2011-01-01

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

  7. Oral vaccination against plague using Yersinia pseudotuberculosis.

    PubMed

    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.

  8. Plague: Frequently Asked Questions

    MedlinePlus

    ... visit this page: About CDC.gov . Plague Home Ecology & Transmission Symptoms Diagnosis & Treatment Maps & Statistics Info for ... periods in the fleas. An illustration of plague ecology in the United States is available. Top of ...

  9. Plague Diagnosis and Treatment

    MedlinePlus

    ... 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 ...

  10. Plague in the genomic area.

    PubMed

    Drancourt, M

    2012-03-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed

    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.

  16. Enzootic plague foci, Algeria

    PubMed Central

    Malek, M.A.; Hammani, A.; Beneldjouzi, A.; Bitam, I.

    2014-01-01

    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. PMID:25834736

  17. Plague in Vienna.

    PubMed

    Velimirovic, B; Velimirovic, H

    1989-01-01

    The history of plague in one city--Vienna, Austria--has been traced from records beginning in the fourteenth century until its disappearance in the eighteenth century. Much of the source material for this review is published for the first time in English and is drawn from records maintained by the city of Vienna at the time of each outbreak. The historical context illustrates the reaction of large populations to deadly disease: fear, helplessness, and acceptance of an ever present threat. Concepts of prophylaxis to ward off the infection were haphazard, empiric, and often dependent on the use of medicaments and treatments that were, in modern terms, irrational. The medical and hygienic concepts of the time were principal impediments to more successful control, as is demonstrated by quotations from official documents dealing with attempts to cope with the epidemic. The development of control measures was painfully slow, and ultimate control was not achieved until socioeconomic improvement and concepts of hygiene both reached the point at which the conditions for the spread of the disease could be minimized.

  18. Amino acid residues 196–225 of LcrV represent a plague protective epitope

    PubMed Central

    Quenee, Lauriane E.; Berube, Bryan J.; Segal, Joshua; Elli, Derek; Ciletti, Nancy A.; Anderson, Deborah; Schneewind, Olaf

    2010-01-01

    LcrV, a protein that resides at the tip of the type III secretion needles of Yersinia pestis, is the single most important plague protective antigen. Earlier work reported monoclonal antibody MAb 7.3, which binds a conformational epitope of LcrV and protects experimental animals against lethal plague challenge. By screening monoclonal antibodies directed against LcrV for their ability to protect immunized mice against bubonic plague challenge, we examined here the possibility of additional protective epitopes. MAb BA5 protected animals against plague, neutralized the Y. pestis type III secretion pathway and promoted opsonophagocytic clearance of bacteria in blood. LcrV residues 196–225 were necessary and sufficient for MAb-BA5 binding. Compared to full length LcrV, a variant lacking its residues 196–225 retained the ability of eliciting plague protection. These results identify LcrV residues 196–225 as a linear epitope that is recognized by the murine immune system to confer plague protection. PMID:20005318

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

    SciTech Connect

    Tully, Damien C. Fares, Mario A.

    2008-12-20

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

    PubMed

    Tully, Damien C; Fares, Mario A

    2008-12-20

    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.

  1. Yersinia pestis Yop Secretion Portein F: Purification, Characterization, and Protective Efficacy Against Bubonic Plague

    DTIC Science & Technology

    2005-03-17

    enterocolitica, Yersinia enterocolitica ; Y. pestis, Yersinia pestis.CA), and used for a recombination reaction with the pDONR201 entry vector (Invitrogen, CA...158 (2002) 401–408. [15] E. Hoiczyk, G. Bloebel, Polymerization of a single protein of the pathogen Yersinia enterocolitica into needles punctures

  2. Plagues at the Gate.

    ERIC Educational Resources Information Center

    Siebert, Charles

    1995-01-01

    Discusses efforts to prevent the global expansion of killer viruses that threaten humans and livestock populations. Focuses on virus research efforts conducted at Plum Island. Profiles the most worrisome of potential plagues. (LZ)

  3. Plague Maps and Statistics

    MedlinePlus

    ... introduced into the United States in 1900, by rat–infested steamships that had sailed from affected areas, ... 1924 through 1925. Plague then spread from urban rats to rural rodent species, and became entrenched in ...

  4. Plagues at the Gate.

    ERIC Educational Resources Information Center

    Siebert, Charles

    1995-01-01

    Discusses efforts to prevent the global expansion of killer viruses that threaten humans and livestock populations. Focuses on virus research efforts conducted at Plum Island. Profiles the most worrisome of potential plagues. (LZ)

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

    PubMed

    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.

  6. Yersinia pestis IS1541 transposition provides for escape from plague immunity.

    PubMed

    Cornelius, Claire A; Quenee, Lauriane E; Elli, Derek; Ciletti, Nancy A; Schneewind, Olaf

    2009-05-01

    Yersinia pestis is perhaps the most feared infectious agent due to its ability to cause epidemic outbreaks of plague disease in animals and humans with high mortality. Plague infections elicit strong humoral immune responses against the capsular antigen (fraction 1 [F1]) of Y. pestis, and F1-specific antibodies provide protective immunity. Here we asked whether Y. pestis generates mutations that enable bacterial escape from protective immunity and isolated a variant with an IS1541 insertion in caf1A encoding the F1 outer membrane usher. The caf1A::IS1541 insertion prevented assembly of F1 pili and provided escape from plague immunity via F1-specific antibodies without a reduction in virulence in mouse models of bubonic or pneumonic plague. F1-specific antibodies interfere with Y. pestis type III transport of effector proteins into host cells, an inhibitory effect that was overcome by the caf1A::IS1541 insertion. These findings suggest a model in which IS1541 insertion into caf1A provides for reversible changes in envelope structure, enabling Y. pestis to escape from adaptive immune responses and plague immunity.

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

    PubMed

    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 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 Cys(273)Ala substitution. Furthermore, macrophages infected by the lcrVC273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis, resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis ΔgshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.IMPORTANCEYersinia pestis, the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of Y. pestis in mouse and rat models for

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

    PubMed Central

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

    2017-01-01

    ABSTRACT 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. PMID:28512097

  9. [Petrarca and the plague].

    PubMed

    Bergdolt, K

    1992-01-01

    The author presents a synopsis of Petrarch's reflections and experiences during the plague of 1348 and the following alterations in Italian society. The great humanist and celebrated poet was an excellent observer of the reactions of his contemporaries and the various cultural and moral consequences of the "Black Death" catastrophe. He feels deep desperation but emphasizes stoic acceptance of fate and Christian humility. His letters concerning plague and death are impressive documents of the "interior life" of European intellectuals in midfourteenth century. They reveal the helplessness of scholastic medical doctors and the crisis of contemporary medicine.

  10. Plague Masquerading as Gastrointestinal Illness

    PubMed Central

    Hull, Harry F.; Montes, Jean M.; Mann, Jonathan M.

    1986-01-01

    In clinical descriptions of human plague, fever and tender lymphadenitis are emphasized and gastrointestinal manifestations are rarely mentioned. A review of 71 human plague cases showed that gastrointestinal symptoms occurred commonly (57%). Vomiting (39%) was the most frequent symptom, with nausea (34%), diarrhea (28%) and abdominal pain (17%) occurring less often. Physicians treating patients who reside in or have recently visited plague-endemic areas should include plague in the differential diagnosis in the presence of gastrointestinal symptoms and fever. PMID:3788132

  11. ["I do not wish to be controversial": the arrival of the plague in Brazil; analysis of a controversy, 1899].

    PubMed

    Nascimento, Dilene Raimundo do; Silva, Matheus Alves Duarte da

    2013-11-30

    This article analyzes a debate brought to the public arena by Jornal do Commercio newspaper in August and September 1899 involving two sanitation officials: Nuno de Andrade, Director-General of Public Health, and Jorge Pinto, Director of Hygiene and Public Welfare of the State of Rio de Janeiro. The issue in question was the measures taken by the federal government to prevent bubonic plague reaching Brazil from Porto, Portugal, where there was an epidemic. The theoretical framework for the analysis is Pierre Bourdieu's notion of field, and Bruno Latour's studies into scientific controversy.

  12. Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele.

    PubMed

    Galvani, Alison P; Slatkin, Montgomery

    2003-12-09

    The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 deletion allele together indicate that it has been intensely selected in Europe. Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure. The prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current frequency can be attributed to bubonic plague. By using a population genetic framework that takes into account the temporal pattern and age-dependent nature of specific diseases, we find that smallpox is more consistent with this historical role.

  13. Plague in a Pediatric Patient: Case Report and Use of Polymerase Chain Reaction as a Diagnostic Aid.

    PubMed

    Drummond, Wendi K; Nelson, Christina A; Fowler, Joe; Epson, Erin E; Mead, Paul S; Lawaczeck, Elisabeth W

    2014-12-01

    We report a case of bubonic plaque in a 7-year-old patient who presented with a core temperature of 107°F, seizures, vomiting, altered mental status, and septic shock. This case highlights the utility of polymerase chain reaction (PCR) as a diagnostic aid for rapid presumptive identification of Yersinia pestis as well as the importance of correlating PCR results with clinical data. We discuss the various manifestations of plague as they relate to infection control, postexposure prophylaxis, antimicrobial therapy, and treatment duration.

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

    PubMed

    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.

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

    PubMed

    Moseng, Ole Georg

    2007-12-13

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

  16. The plague of Athens: epidemiology and paleopathology.

    PubMed

    Littman, Robert J

    2009-10-01

    In 430 BC, a plague struck the city of Athens, which was then under siege by Sparta during the Peloponnesian War (431-404 BC). In the next 3 years, most of the population was infected, and perhaps as many as 75,000 to 100,000 people, 25% of the city's population, died. The Athenian general and historian Thucydides left an eye-witness account of this plague and a detailed description to allow future generations to identify the disease should it break out again. Because of the importance of Thucydides and Athens in Western history and culture, the Plague of Athens has taken a prominent position in the history of the West for the past 2500 years. Despite Thucydides' careful description, in the past 100 years, scholars and physicians have disagreed about the identification of the disease. Based on clinical symptoms, 2 diagnoses have dominated the modern literature on the Athenian plague: smallpox and typhus. New methodologies, including forensic anthropology, demography, epidemiology, and paleopathogy, including DNA analysis, have shed new light on the problem. Mathematical modeling has allowed the examination of the infection and attack rates and the determination of how long it takes a disease to spread in a city and how long it remains endemic. The highly contagious epidemic exhibited a pustular rash, high fever, and diarrhea. Originating in Ethiopia, it spread throughout the Mediterranean. It spared no segment of the population, including the statesman Pericles. The epidemic broke in early May 430 BC, with another wave in the summer of 428 BC and in the winter of 427-426 BC, and lasted 4.5 to 5 years. Thucydides portrays a virgin soil epidemic with a high attack rate and an unvarying course in persons of different ages, sexes, and nationalities.The epidemiological analysis excludes common source diseases and most respiratory diseases. The plague can be limited to either a reservoir diseases (zoonotic or vector-borne) or one of the respiratory diseases associated

  17. Molecular history of plague.

    PubMed

    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.

  18. METHODS OF PLAGUE CONTROL

    PubMed Central

    Simpson, Friench

    1920-01-01

    If we are economically and efficiently to ward off plague we must rid ourselves of the rat. This demands coördination of effort, management, organization and funds. Rat destruction and rat-proofing are preventive measures that fortunately do not involve financial loss, while they will eliminate the dangerous rodent from the homes and environment of men. Imagesp850-ap850-bp850-cp850-d PMID:18010390

  19. An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague

    PubMed Central

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

    2012-01-01

    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×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). 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. PMID:22348169

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

    PubMed

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

    2012-01-01

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

  1. Plague and Climate: Scales Matter

    PubMed Central

    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

  2. Plague and climate: scales matter.

    PubMed

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

    2011-09-01

    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.

  3. [The prevention measures of plague in Hebei from 1946 to 1948].

    PubMed

    Jia, Ge

    2010-05-01

    The plague was seriously occurred in Hebei from 1946 to 1948, which had a great impact on the local social economy and people's life. The public health system was established by the government, and people were instructed about the knowledge of health consciousness and life habits for controlling effectively the plague. The measures of giving medicine freely and social assistance were taken for preventing the plague in the folk. Thus, the plague was controlled in a short time. However, the effect of prevention was limited by the objective conditions. The color of western medicine was showed from these measures, and the "modernity" of the system at that time was indicated.

  4. Plague in Tanzania: an overview.

    PubMed

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

    2013-10-01

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

  5. [Epidemic recrudescence of the Great Plague in Marseille (May-July 1722): excavation of a mass grave].

    PubMed

    Signoli, M; Bello, S; Dutour, O

    1998-01-01

    The return of some infectious disease has stimulated specialists to study historical aspects of human infections. A major model for this study is Yersinia pestis which has had a great impact on human demography due to the fact that it is highly contagious and has a high mortality rate similar to that of the most lethal viral pathogenic agents. We carried out excavation of a mass grave containing the bodies of victims of an outbreak of bubonic plague that occurred in Marseille from 1720 to 1722. More than 200 skeletons were uncovered from the grave known as the Observance (second district in Marseille). In conjunction with laboratory testing, archival records were studied to determine the conditions and dates surrounding the use of this mass grave and to explain certain findings made at the site. This multidisciplinary approach revealed previously unknown facts concerning the Great Plague and provided new insight into recrudescence of the epidemic in 1722.

  6. Viper Plague Project

    DTIC Science & Technology

    2009-07-01

    City-Base, Texas 78235. v List of Figures Figure 1 a. Characteristic plaque formation produced by the Viper Plague bacterium in VH2 cells...10x…………….…..2 Figure 1 b. Characteristic plaque formation produced by the Viper Plaque retrovirus in VH2 cells, 10x………………… 2 Figure 1c. Uninfected...infection lines were also performed. After working with the infected cell lines, it was noted that the bacterium produced a cell-fusion plaque

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

    PubMed Central

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

    2012-01-01

    Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. PMID:23195858

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

    PubMed

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

    2013-03-01

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

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

    PubMed

    Sabbatani, Sergio; Manfredi, Roberto; Fiorino, Sirio

    2012-09-01

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

  10. [Epidemics in the news in Portugal: cholera, plague, typhus, influenza and smallpox, 1854-1918].

    PubMed

    de Almeida, Maria Antónia Pires

    2014-01-01

    In severe health crisis like those of 1854-1856, 1899 and 1918, especially in Porto, where cholera morbus, the bubonic plague, typhus fever, pneumonic influenza and smallpox killed high percentages of the population, the images of the epidemics in the press enable us to identify the scientific knowledge in a country considered peripheral, but which had studies and personnel specialized at the most advanced levels for the time. A database of 6,700 news items and announcements reveals the medical and pharmaceutical knowledge of the second half of the nineteenth and early twentieth centuries, the way it was transmitted and disclosed to the public and the solutions offered by the health authorities. Hygiene was consistently highlighted in the news and announcements.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-02-01

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

  13. Plague, policy, saints and terrorists: a historical survey.

    PubMed

    Lippi, Donatella; Conti, Andrea A

    2002-05-01

    Plague is an infectious disease of humans and animals caused by the bacterium Yersinia pestis. During the Middle Ages millions of people in Europe died from plague, whose current mortality-if untreated-ranges from 50% to 90%. The plague has been a great protagonist in history because it has often been grimly present in the collective events of humans. Its plurisecular history, tied to the whole chain of ecological balance, has had a strong influence on the collective imagination on account of its sudden occurrence and unavoidable mortality. In the past, the passage from contagion to illness ended in death, as human remedies had no effect. The only way to conquer it was invoke the incorruptible spirit of a saint. Therefore, in the past, the major plague icons were saints to whom ordinary people attributed a fame for healing. More recently, many epidemic diseases have ceded place to biological weapons, and terrorists have become the modern icons of such a threatening reality. As a matter of fact, bioterrorism has become a great public health and infection control threat, and, among the number of potential biological agents, plague has assumed a key role. Copyright 2002 The British Infection Society.

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

    PubMed

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

    2014-01-01

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

  15. A Yersinia pestis tat Mutant Is Attenuated in Bubonic and Small-Aerosol Pneumonic Challenge Models of Infection but Not As Attenuated by Intranasal Challenge

    PubMed Central

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

    2014-01-01

    Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge. PMID:25101850

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

    PubMed

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

    2007-01-22

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

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

    PubMed

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

    2007-11-01

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

  18. Design and Testing for a Nontagged F1-V Fusion Protein as Vaccine Antigen Against Bubonic and Pneumonic Plague

    DTIC Science & Technology

    2005-08-01

    effector protein that is transported into the eukaryotic host cell along with several other Yersinia outer proteins ( YOPs ) (1) by a contact-dependent Type...III secretion system during infection (20). V protein serves a central role for patho- genesis as a regulator of the transfer of YOPs and is itself a...Medical Research Institute of Infectious Dis- eases; YOP , Yersinia outer protein . (2) Achtman, M.; Morelli, G.; Zhu, P.; Wirth, T.; Diehl, I.; Kusecek

  19. "Pink plague" changes course.

    PubMed

    Chauvin, L

    1993-03-01

    By October 1992, the government's Special Program to Control AIDS (PECOS) registered 717 cases of the disease in Peru; however, the number of acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) cases could number thousands. PECOS estimates that the number of cases of HIV is doubling every 2 years. One of the main reasons for the continued spread of HIV is the common perception that the pink plague, as AIDS is called here, affects only homosexuals. While 85% of sexually transmitted HIV and AIDS cases are among gay and bisexual men, in the past 4 years a large number of new cases has been registered among heterosexuals, especially women. In 1987, the ratio of AIDS cases among men and women was approximately 15 to 1. Today, the male to female ratio is 7 to 1. Most people working on AIDS say that the changing profile of the epidemic in Peru is caused by the high costs of prevention programs and the lack of information on the disease, which drastically raise the number of people in high risk groups. Peru's ongoing economic crisis has eaten into the budgets of nongovernment organization's (NGOs) AIDS prevention campaigns and has pushed treatment out of the reach of many people. In 1991, 3 television commercials developed by PECOS to promote the use of condoms were blocked by the Health Ministry. One of the groups that fought against campaigns promoting condom use was the Association of Catholic Doctors. The only way to organize an effective program is through a joint effort that brings together the government, NGOs, and other private and public institutions. Cooperation was demonstrated through the actions carried out for World AIDS Day, when more than 16 public, NGO, and government organizations were involved in a variety of AIDS information activities. In 1993, about 30 NGOs will begin actively working with Peru's Health Ministry to coordinate activities.

  20. The threatened plague.

    PubMed

    Epstein, P

    1997-01-01

    This article discusses changes in disease patterns affecting human health that may be related to environmental and social changes in the world. The World Health Report reveals that 30 new diseases emerged in the past 20 years. Old diseases are becoming resistant to new drugs. Infectious diseases that were in decline are spreading: diphtheria, whooping cough, and measles. Illnesses such as malaria, fevers, cholera, and rodent-borne viruses are becoming more frequent. Diseases that are transmitted by animals or water are related to environmental and social changes. Degraded environments are susceptible to the appearance of opportunistic species, such as weeds, rodents, insects, and microorganisms. Stable environments support the welfare of large predators and control opportunistic species. Owls, coyotes, and snakes eat rodents that carry Lyme disease ticks and a variety of viruses, plague, and bacteria. Reptiles, birds, spiders, ladybugs, bats, and fish consume larvae and mosquitoes that cause malaria and fevers. Habitat loss and fragmentation, monocultures, excessive use of toxic chemicals, climate change, and weather instability are widespread global changes that reduce the predator population. Small wilderness habitats favor pests. Monocultures reduce genetic diversity and increase vulnerability. Excessive use of pesticides harms birds and helpful insects. A sign of a failing ecosystem is the population explosion of pests and disequilibrium. The Environmental Distress Syndrome is characterized as: 1) emerging infectious diseases, 2) loss of biodiversity, 3) increased generalist species and decreased specialist species, 4) declines in specific specialists, such as pollinators responsible for preservation of flowering plants, and 5) increased coastal algal blooms. The impacts of disease mean considerable costs to humans, agriculture, and livestock. Loss of resources is also costly.

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

    PubMed

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

    2010-12-16

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

  2. Historians and plagues in pre-industrial Italy over the longue durée.

    PubMed

    Henderson, John

    2003-01-01

    This essay deals with plague and plagues in renaissance and early modern Europe over the longue durée, principally from a methodological perspective. I shall combine an historiographical approach with an historical account of developing reactions to plague and in passing compare measures to cope in the early sixteenth century with reactions to the impact of the Great Pox or the Mal de Naples. I shall concentrate on southern Europe and in particular on Italy and my aim is to re-assess the historiography of plague through the lens of some of the more recent Anglo-Saxon literature in this field. In the process I shall outline some of the debates within the field and end with some general methodological observations drawn from early modern Italy.

  3. [The great plague of Athens 430 BC].

    PubMed

    Frøland, Anders

    2010-01-01

    The plague of Athens in 430-426 BC has puzzled scholars and doctors for generations as to the aetiology of this deadly disease that had profound influence on the outcome of the Great Peloponnesian War (431-404 BC). Like several thousand soldiers and civilians, Pericles succumbed to the plague in 429. The main opponent to Athens was Sparta. Sparta had a formidable land based army, whereas Athens dominated at sea. Pericles' strategy was to shelter the whole of Attica's population within the protecting walls of Athens and Piraeus and the long walls connecting the two cities, while the Spartans ravaged Attica during the summer months. The result was a tremendous overcrowding in the two cities. The number of inhabitants rose from 145,000 to more than half a million. Therefore optimal conditions for the outbreak of an epidemic of any contagious disease were present. The Athenian general and historian Thucydides (455-396 BC), though not a medical man himself, has provided us with a very clear and precise description of the disease, which he himself contracted but survived. A huge number of modern aetiologies has been proposed, but none has so far been able to match Thucydides' clinical picture in all details. Presumably the disease has changed so much during the past 2400 years as not to be recognisable any more or it has totally disappeared.

  4. Red Plague Control Plan (RPCP)

    NASA Technical Reports Server (NTRS)

    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.

  5. Plague - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Plague URL of this page: https://medlineplus.gov/languages/plague.html Other topics A-Z A B C ... V W XYZ List of All Topics All Plague - Multiple Languages To use the sharing features on ...

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

    PubMed

    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.

  7. AN EPIDEMIC OF PNEUMONIC PLAGUE

    PubMed Central

    Kellogg, W. H.

    1920-01-01

    Dr. Kellogg calls on health authorities to wake from their apathy with reference to plague in California, and instead of restrictive measures to adopt an aggressive warfare. He points out that there is real danger to the country and urges adequate appropriations to exterminate the animal disease carriers while this may be done with certainty. PMID:18010342

  8. Zoonotic Focus of Plague, Algeria

    PubMed Central

    Bitam, Idir; Baziz, Belkacem; Rolain, Jean-Marc; Belkaid, Miloud

    2006-01-01

    After an outbreak of human plague, 95 Xenopsylla cheopis fleas from Algeria were tested for Yersinia pestis with PCR methods. Nine fleas were definitively confirmed to be infected with Y. pestis biovar orientalis. Our results demonstrate the persistence of a zoonotic focus of Y. pestis in Algeria. PMID:17326957

  9. Are carnivores universally good sentinels of plague?

    PubMed

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

    2009-10-01

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

  10. Are Carnivores Universally Good Sentinels of Plague?

    PubMed Central

    Collinge, Sharon K.; Bai, Ying; Ray, Chris

    2009-01-01

    Abstract Sylvatic plague, caused by the bacterium Yersinia pestis, is a flea-borne disease that primarily affects rodents but has been detected in over 200 mammal species worldwide. Mammalian carnivores are routinely surveyed as sentinels of local plague activity, since they can present antibodies to Y. pestis infection but show few clinical signs. In Boulder County, Colorado, USA, plague epizootic events are episodic and occur in black-tailed prairie dogs. Enzootic hosts are unidentified as are plague foci. For three years, we systematically sampled carnivores in two distinct habitat types to determine whether carnivores may play a role in maintenance or transmission of Y. pestis and to identify habitats associated with increased plague prevalence. We sampled 83 individuals representing six carnivore species and found only two that had been exposed to Y. pestis. The low overall rate of plague exposure in carnivores suggests that plague may be ephemeral in this study system, and thus we cannot draw any conclusions regarding habitat-associated plague foci or temporal changes in plague activity. Plague epizootics involving prairie dogs were confirmed in this study system during two of the three years of this study, and we therefore suggest that the targeting carnivores to survey for plague may not be appropriate in all ecological systems. PMID:18973449

  11. [Plague in Rostov Province (its history, epidemiology, epizootiology, control measures and prevention)].

    PubMed

    Kulov, G I; Kuchin, V V; Levchishina, G I; Danilkin, A P; Sherstneva, T A; Antonian, B Kh

    1996-01-01

    In the first third of the twentieth century, the overgrazing of cattle in the eastern districts of the modern Rostov Province yielded deserts in the places of virgin steppes and created favourable conditions for the enlargement of an area for the small souslik, a main carrier of plague in the natural focus of the northwestern Caspian Sea Region. On the above territories, this gave rise to a new natural focus of plague. Its liquidation required many-year goal-oriented efforts of large collective bodies of plaguologists and great material costs. The settlements of small sousliks exist on the above territories today and the activation of a natural focus of plague in the adjacent Kalmykia generate a need for enhancing plague epidemiological surveillance in the eastern districts of the Rostov Province today.

  12. Plague and landscape resilience in premodern Iceland

    PubMed Central

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

    2012-01-01

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

  13. Plague and landscape resilience in premodern Iceland.

    PubMed

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

    2012-03-06

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

  14. The climatic context of major plague outbreaks in late medieval England

    NASA Astrophysics Data System (ADS)

    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.

  15. Immune defense against pneumonic plague

    PubMed Central

    Smiley, Stephen T.

    2009-01-01

    Summary Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection. PMID:18837787

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

    PubMed

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

    2012-10-01

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

  17. Roles of Chaperone/Usher Pathways of Yersinia pestis in a Murine Model of Plague and Adhesion to Host Cells

    PubMed Central

    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

  18. Cethromycin-mediated protection against the plague pathogen Yersinia pestis in a rat model of infection and comparison with levofloxacin.

    PubMed

    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.

  19. Human Plague - United States, 2015.

    PubMed

    Kwit, Natalie; Nelson, Christina; Kugeler, Kiersten; Petersen, Jeannine; Plante, Lydia; Yaglom, Hayley; Kramer, Vicki; Schwartz, Benjamin; House, Jennifer; Colton, Leah; Feldpausch, Amanda; Drenzek, Cherie; Baumbach, Joan; DiMenna, Mark; Fisher, Emily; Debess, Emilio; Buttke, Danielle; Weinburke, Matthew; Percy, Christopher; Schriefer, Martin; Gage, Ken; Mead, Paul

    2015-08-28

    Since April 1, 2015, a total of 11 cases of human plague have been reported in residents of six states: Arizona (two), California (one), Colorado (four), Georgia (one), New Mexico (two), and Oregon (one). The two cases in Georgia and California residents have been linked to exposures at or near Yosemite National Park in the southern Sierra Nevada Mountains of California. Nine of the 11 patients were male; median age was 52 years (range = 14-79 years). Three patients aged 16, 52, and 79 years died.

  20. [Is not plague a "protonosis"? (the role of Protozoa in the epizootiology of plague)].

    PubMed

    Domaradskiĭ, I V

    1999-01-01

    The author expounds the idea that soil protozoa, whose vegetative forms and cysts can harbor the plague agent for fairly prolonged periods of time, can be a major player in the epizootiology of plague. It is also postulated that the symbiotic protozoa of the digestive tract of rodents and lagomorpha can also be a reservoir of the plague agent. If this is so, among apparent epizootic cycles in mammalians in wild plague foci one should look for Yersinia pestis in the protozoa from the burrows of their primary and secondary carriers. Because parasitism of bacteria in one-celled animals is essentially epizootic, plague epizootics are presumed to be a permanent process.

  1. [Ecological-geographic landscapes of natural plague foci in China VIII. Typing of natural plague foci].

    PubMed

    Fang, Xi-ye; Liu, Qi-yong; Xu, Lei; Zhou, Dong-sheng; Cui, Yu-jun; Dong, Xing-qi; Zhang, Rong-zu; Gu, Shao-hua; Ye, Cai-de; Yang, Rui-fu

    2013-01-01

    Since plague is an important natural focus zoonosis, the typing of natural plague foci becomes one of the elements in understanding the nature and developing related prevention program of the disease. Natural foci of plague are composed by four fundamental parts which include Eco-geographical landscape (natural plague foci), hosts, vectors and pathogens (Yersinia pestis) that comprehensively interact through the large temporal scale of evolution. Human activities have had great impact on the foci of natural plague. Based on the published serial research papers, we tried to integrate the knowledge of each factor in natural plague foci and focusing on theoretical aspects, so as to strengthen the prevention and surveillance programs of plague to be extrapolated to other zoonosis.

  2. [Eco-geographic landscapes of natural plague foci in China I. Eco-geographic landscapes of natural plague foci].

    PubMed

    Fang, Xi-ye; Xu, Lei; Liu, Qi-yong; Zhang, Rong-zu

    2011-12-01

    To study the eco-geographic landscapes of natural plague foci, in China. According to the surveillance records on plague epidemics and the eco-geographic landscapes of natural plague foci based on the county level, the criterion for classifying the ecological geographic zone of Chinese natural plague foci was established. 12 types and 19 subtypes of eco-geographic landscapes on Chinese natural plague foci were identified. Scientific basis for Chinese natural plague foci classification was provided.

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

    PubMed

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

    2001-05-01

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

  4. Expression of an immunogenic F1-V fusion protein in lettuce as a plant-based vaccine against plague.

    PubMed

    Rosales-Mendoza, Sergio; Soria-Guerra, Ruth E; Moreno-Fierros, Leticia; Alpuche-Solís, Angel G; Martínez-González, Luzmila; Korban, Schuyler S

    2010-07-01

    Yersinia pestis is a pathogenic agent that causes the bubonic and pneumonic plague. The development of an efficient and low-cost oral vaccine against these diseases is highly desirable. In this study, the immunogenic fusion protein F1-V from Y. pestis was introduced into lettuce via Agrobacterium-mediated transformation, and putative transgenic lines were developed. The presence of the transgene in these putative transgenic lines was determined using polymerase chain reaction (PCR), and transgene integration and transgene copy number were confirmed following Southern blot analysis. The presence of specific F1-V transcripts was confirmed by reverse-transcriptase (RT)-PCR. Using monoclonal antibodies, ELISA and western blot analysis revealed that the expected antigenic F1-V protein was successfully expressed in transgenic lines. Mice immunized subcutaneously with lettuce expressing the F1-V antigen developed systemic humoral responses as 'proof of concept' of using lettuce as a production platform for the F1-V immunogen that could be used as a candidate plant-based vaccine against plague.

  5. New records of sylvatic plague in Kansas

    USGS Publications Warehouse

    Cully, J.F.; Carter, L.G.; Gage, K.L.

    2000-01-01

    Sylvatic plague, or plague of wild rodents is caused by Yersinia pestis and entered California (USA) from Asia about 1899. Extensive sampling during the 1930's and 1940's documented the spread of plague to approximately its current distribution in North America. Records from the Centers for Disease Control and Prevention document plague in Kansas (USA) between 1945 and 1950, but since then there has been no documentation of plague in the state. Following a die-off of a black-tailed prairie dog (Cynomys ludovicianus) colony on the Cimarron National Grassland, in the southwestern corner of Kansas (37??10???N, 101??45???W), we sampled fleas from burrows in June 1997, and tested them for Yersinia pestis. Twelve of 13 pools of Oropsyla hirsuta and one of two Pulex sp. were positive. A similar sample of fleas, from another colony where black-tailed prairie dogs were active at the time, yielded no positive fleas.

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

    PubMed

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

    2013-03-01

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

  7. Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Lane, M. Chelsea; Lenz, Jonathan D.

    2013-01-01

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

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

    PubMed

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

    2014-11-01

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

  10. Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

    PubMed Central

    Erickson, D. L.

    2013-01-01

    Transmission by fleabite is a relatively recent evolutionary adaptation of Yersinia pestis, the bacterial agent of bubonic plague. To produce a transmissible infection, Y. pestis grows as an attached biofilm in the foregut of the flea vector. Biofilm formation both in the flea foregut and in vitro is dependent on an extracellular matrix (ECM) synthesized by the Yersinia hms gene products. The hms genes are similar to the pga and ica genes of Escherichia coli and Staphylococcus epidermidis, respectively, that act to synthesize a poly-β-1,6-N-acetyl-d-glucosamine ECM required for biofilm formation. As with extracellular polysaccharide production in many other bacteria, synthesis of the Hms-dependent ECM is controlled by intracellular levels of cyclic-di-GMP. Yersinia pseudotuberculosis, the food- and water-borne enteric pathogen from which Y. pestis evolved recently, possesses identical hms genes and can form biofilm in vitro but not in the flea. The genetic changes in Y. pestis that resulted in adapting biofilm-forming capability to the flea gut environment, a critical step in the evolution of vector-borne transmission, have yet to be identified. During a flea bite, Y. pestis is regurgitated into the dermis in a unique biofilm phenotype, and this has implications for the initial interaction with the mammalian innate immune response. PMID:18453279

  11. Yersinia pestis biofilm in the flea vector and its role in the transmission of plague.

    PubMed

    Hinnebusch, B J; Erickson, D L

    2008-01-01

    Transmission by fleabite is a relatively recent evolutionary adaptation of Yersinia pestis, the bacterial agent of bubonic plague. To produce a transmissible infection, Y. pestis grows as an attached biofilm in the foregut of the flea vector. Biofilm formation both in the flea foregut and in vitro is dependent on an extracellular matrix (ECM) synthesized by the Yersinia hms gene products. The hms genes are similar to the pga and ica genes of Escherichia coli and Staphylococcus epidermidis, respectively, that act to synthesize a poly-beta-1,6-N-acetyl-d-glucosamine ECM required for biofilm formation. As with extracellular polysaccharide production in many other bacteria, synthesis of the Hms-dependent ECM is controlled by intracellular levels of cyclic-di-GMP. Yersinia pseudotuberculosis, the food- and water-borne enteric pathogen from which Y. pestis evolved recently, possesses identical hms genes and can form biofilm in vitro but not in the flea. The genetic changes in Y. pestis that resulted in adapting biofilm-forming capability to the flea gut environment, a critical step in the evolution of vector-borne transmission, have yet to be identified. During a flea bite, Y. pestis is regurgitated into the dermis in a unique biofilm phenotype, and this has implications for the initial interaction with the mammalian innate immune response.

  12. Prospects for new plague vaccines.

    PubMed

    Feodorova, Valentina A; Corbel, Michael J

    2009-12-01

    The potential application of Yersinia pestis for bioterrorism emphasizes the urgent need to develop more effective vaccines against airborne infection. The current status of plague vaccines has been reviewed. The present emphasis is on subunit vaccines based on the F1 and LcrV antigens. These provide good protection in animal models but may not protect against F1 strains with modifications to the type III secretion system. The duration of protection against pneumonic infection is also uncertain. Other strategies under investigation include defined live-attenuated vaccines, DNA vaccines, mucosal delivery systems and heterologous immunization. The live-attenuated strain Y. pestis EV NIIEG protects against aerosol challenge in animal models and, with further modification to reduce residual virulence and to optimize respiratory protection, it could provide a shortcut to improved vaccines. The regulatory problems inherent in licensing vaccines for which efficacy data are unavailable and their possible solutions are discussed herein.

  13. Epizootiologic parameters for plague in Kazakhstan.

    PubMed

    Begon, Michael

    2006-02-01

    Reliable estimates are lacking of key epizootiologic parameters for plague caused by Yersinia pestis infection in its natural reservoirs. We report results of a 3-year longitudinal study of plague dynamics in populations of a maintenance host, the great gerbil (Rhombomys opimus), in 2 populations in Kazakhstan. Serologic results suggest a mid-summer peak in the abundance of infectious hosts and possible transmission from the reservoir to humans. Decrease in antibody titer to an undetectable level showed no seasonal pattern. Our findings did not support the use of the nitroblue-tetrazolium test characterization of plague-infected hosts. Y. pestis infection reduced survival of otherwise asymptomatic hosts.

  14. Epizootiologic Parameters for Plague in Kazakhstan

    PubMed Central

    Klassovskiy, Nikolay; Ageyev, Vladimir; Suleimenov, Bakhtiar; Atshabar, Bakhyt; Bennett, Malcolm

    2006-01-01

    Reliable estimates are lacking of key epizootiologic parameters for plague caused by Yersinia pestis infection in its natural reservoirs. We report results of a 3-year longitudinal study of plague dynamics in populations of a maintenance host, the great gerbil (Rhombomys opimus), in 2 populations in Kazakhstan. Serologic results suggest a mid-summer peak in the abundance of infectious hosts and possible transmission from the reservoir to humans. Decrease in antibody titer to an undetectable level showed no seasonal pattern. Our findings did not support the use of the nitroblue-tetrazolium test characterization of plague-infected hosts. Y. pestis infection reduced survival of otherwise asymptomatic hosts. PMID:16494753

  15. Discovery of the Plague Pathogen: Lessons Learned.

    PubMed

    Yang, Ruifu; Butler, Thomas

    2016-01-01

    Plague resulted in three pandemics in history; however, its causative pathogen was isolated until the third pandemic in Hong Kong in 1894. At that time, two famous researchers, Dr. Alexandre Yersin and Dr. Shibasaburo Kitasato, went to HK, in order to identify the pathogen. The two great researchers had done a lot of work to isolate and identify the causative pathogen. However, Dr. Alexandre Yersin reported the real pathogen for plague, and we now acknowledge his work by nominating the pathogen's genus as Yersinia. In this chapter, we discussed the lessons learned from the two researchers' experience on isolation and identification of plague pathogen.

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

    PubMed

    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.

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

    PubMed

    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.

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

    USGS Publications Warehouse

    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.

  19. The natural history and incidence of Yersinia pestis and prospects for vaccination.

    PubMed

    Williamson, E D; Oyston, P C F

    2012-07-01

    Plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. This paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. It reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. Current approaches to vaccine development to protect against pneumonic, as well as bubonic, plague are also reviewed. The considerable challenges in achieving a vaccine which is licensed for human use and which will comprehensively protect against this serious human pathogen are assessed.

  20. Pneumonic Plague Outbreak, Northern Madagascar, 2011

    PubMed Central

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

    2015-01-01

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

  1. Pneumonic plague outbreak, Northern Madagascar, 2011.

    PubMed

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

    2015-01-01

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

  2. The plague and its place in history.

    PubMed

    Leavesley, J H

    1979-09-01

    An outline is presented of the various pan-epidemics of a disease which has been in the past one of mankind's greatest scourges--the plague. Its pathogenesis, spread and effect on the course of history from biblical times until the seventeenth century is traced with a detailed review of the origins of the Black Death. The opinion is forwarded that plague has had a greater impact on the course of human history than any war or any other single disease.

  3. Human Plague Risk: Spatial-Temporal Models

    NASA Technical Reports Server (NTRS)

    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).

  4. DIAGNOSIS AND DETECTION OF RODENT PLAGUE

    PubMed Central

    Williams, C. L.

    1920-01-01

    Stories of his own observations by one who has had experience are the most valuable kind of lessons. This authority places before his readers details of the diagnosis of plague and practical laboratory methods. He outlines the essential features of technique and determination clearly and accurately and has here really a preparatory course in plague detection that it is not easy to get from books. Imagesp864-a PMID:18010391

  5. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015

    PubMed Central

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

    2017-01-01

    During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak. PMID:28221119

  6. Ecology of plague in Africa: response of indigenous wild rodents to experimental plague infection

    PubMed Central

    Isaäcson, Margaretha; Taylor, Paul; Arntzen, Lorraine

    1983-01-01

    The Mastomys natalensis species complex, subdivided into genetically distinct species having diploid chromosome numbers 2n = 32 and 2n = 36, is a reservoir for several zoonoses including Lassa fever and plague. This report describes a study to determine whether these sibling species and three other rodent species have different potential as reservoirs for plague. It was found that M. natalensis (2n = 32) was significantly more resistant to experimental plague infection (50% survived inoculation with 120 000 Yersinia pseudotuberculosis subsp. pestis) than was M. coucha (2n = 36) (none of which survived doses of 190 Y. pseudotuberculosis subsp.pestis). In descending order of resistance were M. natalensis, Aethomys chrysophilus, M. coucha, Tatera leucogaster and A. namaquensis. No A. namaquensis survived inoculation of 10 or more plague bacilli. Previous reports on susceptibility to plague or other infections, which were based exclusively on findings in the universally distributed laboratory-bred Mastomys, are thus not necessarily applicable to the M. natalensis species as a whole but probably only to M. coucha. The Y. pseudotuberculosis subsp. pestis fraction-1 passive haemagglutination test appeared to be relatively insensitive in that only 5 out of 47 animals surviving experimental plague infection showed specific antibodies 6 weeks after challenge. The geographic distribution of human plague in southern Africa corresponds closely with that of the plague-susceptible species, M. coucha, while the resistant species, M. natalensis, predominates in areas where human plague has not been recorded. The role of A. namaquensis in the ecology of plague needs to be carefully studied and its possible importance in plague research should be investigated further. PMID:6345015

  7. Ecology of plague in Africa: response of indigenous wild rodents to experimental plague infection.

    PubMed

    Isaäcson, M; Taylor, P; Arntzen, L

    1983-01-01

    The Mastomys natalensis species complex, subdivided into genetically distinct species having diploid chromosome numbers 2n = 32 and 2n = 36, is a reservoir for several zoonoses including Lassa fever and plague. This report describes a study to determine whether these sibling species and three other rodent species have different potential as reservoirs for plague. It was found that M. natalensis (2n = 32) was significantly more resistant to experimental plague infection (50% survived inoculation with 120 000 Yersinia pseudotuberculosis subsp. pestis) than was M. coucha (2n = 36) (none of which survived doses of 190 Y. pseudotuberculosis subsp.pestis). In descending order of resistance were M. natalensis, Aethomys chrysophilus, M. coucha, Tatera leucogaster and A. namaquensis. No A. namaquensis survived inoculation of 10 or more plague bacilli.Previous reports on susceptibility to plague or other infections, which were based exclusively on findings in the universally distributed laboratory-bred Mastomys, are thus not necessarily applicable to the M. natalensis species as a whole but probably only to M. coucha. The Y. pseudotuberculosis subsp. pestis fraction-1 passive haemagglutination test appeared to be relatively insensitive in that only 5 out of 47 animals surviving experimental plague infection showed specific antibodies 6 weeks after challenge.The geographic distribution of human plague in southern Africa corresponds closely with that of the plague-susceptible species, M. coucha, while the resistant species, M. natalensis, predominates in areas where human plague has not been recorded. The role of A. namaquensis in the ecology of plague needs to be carefully studied and its possible importance in plague research should be investigated further.

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

    PubMed Central

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

    2011-01-01

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

  9. Plague in Africa from 1935 to 1949

    PubMed Central

    Davis, D. H. S.

    1953-01-01

    The history of plague in Africa during the period 1935-49 is reviewed. Much of the information derives from a questionnaire sent to all African territories in 1950. The annual incidence of plague in Africa declined, particularly from 1946 onwards. In 1949, under 400 cases were reported, as compared with over 6,000 in 1935. By the end of 1949, plague was still active in the Belgian Congo, Kenya and Tanganyika, Madagascar, and southern Africa. No cases were reported from Egypt, Tunisia, Algeria, Morocco, Senegal, or Uganda during 1949. A comparison of the seasonal incidence of plague with prevailing atmospheric conditions (temperature and rainfall) in African territories shows that human plague is more frequent in warm moist weather—60°-80°F (15°-27°C)—than in hot dry, or cold, weather—over 80°F (27°C) or under 60°F (15°C). The highlands of equatorial Africa and of Madagascar appear to provide the optimum environment for the persistence of plague on the domestic (murine) plane and the high-veld and Kalahari of southern Africa on the sylvatic plane. The rat (Rattus rattus) and the multimammate mouse (R. (Mastomys) natalensis) and their fleas Xenopsylla brasiliensis and X. cheopis appear to be mainly responsible for the persistence of the reservoir in the East African highlands; R. rattus and X. cheopis play this role in Madagascar. The gerbils (Tatera and Desmodillus) and their burrow fleas X. philoxera and X. piriei are the main reservoirs of plague in southern Africa. Within these areas, Pasteurella pestis finds an environment suitable for its continued survival; the conditions seem to be comparable to those defined as obtaining in endemic centres in India. Elsewhere in Africa such endemic centres do not appear to exist. PMID:13115987

  10. [The epidemiological transition and the conquest of plague].

    PubMed

    Benedictow, O J

    1994-12-10

    In 1971, Abdel R. Omran, the epidemiologist, launched the concepts the epidemic transition and the demographic transition. Assuming that the epidemic and demographic structures of all preindustrial societies were similar, Omran attached these concepts to the epidemic and demographic transitions of the nineteenth century. He indicated that these were the only epidemic and demographic transitions in history. In this paper, it is argued that this assertion is untenable. Historically, there have been many societal transitions implying concurrent and interactive epidemic and demographic transitions. Two major historical events have been selected for illustrative purposes. The emergence of the western demographic system and the advent of plague in 1347 had dramatic impacts on epidemic and demographic conditions. Successful combat of plague, first in Italy, was organized with increasing efficiency from the second half of the fifteenth century on the basis of miasmatic-contagionist epidemiological notions. The antiepidemic organizations developed in this combat were efficient also against most other important epidemic diseases. The rise of antiepidemic organizations contributed to transitional change in epidemic and demographic structures with substantial impact on broader societal processes of modernization. These transitions preceded and conditioned the transitional processes referred to by Omran.

  11. Mountain plover responses to plague in Montana.

    PubMed

    Dinsmore, Stephen J; Smith, Mark D

    2010-01-01

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

  12. Burrowing Owls, Pulex irritans, and Plague.

    PubMed

    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.

  13. Yersinia pestis halotolerance illuminates plague reservoirs

    PubMed Central

    Malek, Maliya Alia; Bitam, Idir; Levasseur, Anthony; Terras, Jérôme; Gaudart, Jean; Azza, Said; Flaudrops, Christophe; Robert, Catherine; Raoult, Didier; Drancourt, Michel

    2017-01-01

    The plague agent Yersinia pestis persists for years in the soil. Two millennia after swiping over Europe and North Africa, plague established permanent foci in North Africa but not in neighboring Europe. Mapping human plague foci reported in North Africa for 70 years indicated a significant location at <3 kilometers from the Mediterranean seashore or the edge of salted lakes named chotts. In Algeria, culturing 352 environmental specimens naturally containing 0.5 to 70 g/L NaCl yielded one Y. pestis Orientalis biotype isolate in a 40 g/L NaCl chott soil specimen. Core genome SNP analysis placed this isolate within the Y. pestis branch 1, Orientalis biovar. Culturing Y. pestis in broth steadily enriched in NaCl indicated survival up to 150 g/L NaCl as L-form variants exhibiting a distinctive matrix assisted laser desorption-ionization time-of-flight mass spectrometry peptide profile. Further transcriptomic analyses found the upregulation of several outer-membrane proteins including TolC efflux pump and OmpF porin implied in osmotic pressure regulation. Salt tolerance of Y. pestis L-form may play a role in the maintenance of natural plague foci in North Africa and beyond, as these geographical correlations could be extended to 31 plague foci in the northern hemisphere (from 15°N to 50°N). PMID:28054667

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

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Biggins, Dean E.

    2009-01-01

    Here, we note a potentially pivotal role for fleas. These epizootic plague vectors should be closely studied with newer more exacting methods to determine their potential to serve as participants in or accomplices to a plague persistence reservoir.

  15. Impact of the plague in Ancient Greece.

    PubMed

    Soupios, M A

    2004-03-01

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

  16. Current challenges in the development of vaccines for pneumonic plague

    PubMed Central

    Smiley, Stephen T

    2008-01-01

    Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

  17. Successful Treatment of Human Plague with Oral Ciprofloxacin.

    PubMed

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

    2017-03-01

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

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

    USGS Publications Warehouse

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

    2009-01-01

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

  19. Wild Felids as Hosts for Human Plague, Western United States

    PubMed Central

    Tracey, Jeff A.; Franklin, Sam P.; Schmit, Virginia L.; MacMillan, Martha L.; Gage, Kenneth L.; Schriefer, Martin E.; Logan, Kenneth A.; Sweanor, Linda L.; Alldredge, Mat W.; Krumm, Caroline; Boyce, Walter M.; Vickers, Winston; Riley, Seth P.D.; Lyren, Lisa M.; Boydston, Erin E.; Fisher, Robert N.; Roelke, Melody E.; Salman, Mo; Crooks, Kevin R.; VandeWoude, Sue

    2009-01-01

    Plague seroprevalence was estimated in populations of 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 in nondomestic felid hosts to better understand the role of these species in disease persistence and transmission. PMID:19961691

  20. Successful Treatment of Human Plague with Oral Ciprofloxacin

    PubMed Central

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

    2017-01-01

    The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague. PMID:28125398

  1. [The plague in Finland in 1710].

    PubMed

    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.

  2. Saving Resources with Plagues in Genetic Algorithms

    SciTech Connect

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

    2004-06-15

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

  3. [Role of burrow microbiocenosis in plague enzootia].

    PubMed

    Udovikov, A I; Grigor'eva, G V; Tolokonnikova, S I; Iakovlev, S A; Tarasov, M A; Sludskiĭ, A A

    2009-01-01

    The paper analyzes relationships of the plague bacilli to the representatives of different types of living organisms inhabiting the burrows. The authors give their own data on the qualitative and quantitative composition of indicoles of the burrow of little sousliks (Spermophillus pygmaeus). They assess the role of mutagenic agents in burrow microbiocenoses.

  4. Expression of the Plague Plasminogen Activator in Yersinia pseudotuberculosis and Escherichia coli

    PubMed Central

    Kutyrev, V.; Mehigh, R. J.; Motin, V. L.; Pokrovskaya, M. S.; Smirnov, G. B.; Brubaker, R. R.

    1999-01-01

    Enteropathogenic yersiniae (Yersinia pseudotuberculosis and Yersinia enterocolitica) typically cause chronic disease as opposed to the closely related Yersinia pestis, the causative agent of bubonic plague. It is established that this difference reflects, in part, carriage by Y. pestis of a unique 9.6-kb pesticin or Pst plasmid (pPCP) encoding plasminogen activator (Pla) rather than distinctions between shared ∼70-kb low-calcium-response, or Lcr, plasmids (pCD in Y. pestis and pYV in enteropathogenic yersiniae) encoding cytotoxic Yops and anti-inflammatory V antigen. Pla is known to exist as a combination of 32.6-kDa (α-Pla) and slightly smaller (β-Pla) outer membrane proteins, of which at least one promotes bacterial dissemination in vivo and degradation of Yops in vitro. We show here that only α-Pla accumulates in Escherichia coli LE392/pPCP1 cultivated in enriched medium and that either autolysis or extraction of this isolate with 1.0 M NaCl results in release of soluble α and β forms possessing biological activity. This process also converted cell-bound α-Pla to β-Pla and smaller forms in Y. pestis KIM/pPCP1 and Y. pseudotuberculosis PB1/+/pPCP1 but did not promote solubilization. Pla-mediated posttranslational hydrolysis of pulse-labeled Yops in Y. pseudotuberculosis PB1/+/pPCP1 occurred more slowly than that in Y. pestis but was otherwise similar except for accumulation of stable degradation products of YadA, a pYV-mediated fibrillar adhesin not encoded in frame by pCD. Carriage of pPCP by Y. pseudotuberculosis did not significantly influence virulence in mice. PMID:10024583

  5. [The people's mentality confronting plague in the Ming Dynasty].

    PubMed

    Chen, Xu

    2013-03-01

    The social influence of plague was not only confined to its pathogenicity, but also its close relationship with the people's mentality. According to the historical materials of the Ming Dynasty, there were 2 kinds of mentalities when confronting with the prevalence of plague: negative and positive. The former included fear, helplessness, depression and superstition etc., and the latter included intelligence, consolation, thanksgiving and vigour etc. The negative passive mentality didn't help to fight effectively against the plague, or might even aggravate its prevalence. However, the positive mentality helped ameliorate and control the plague, and also the rehabilitation of the order of production and living order after the plague.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    Priel, Beatriz

    2007-12-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:27170642

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

    PubMed

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

    PubMed

    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.

  14. Recent Findings Regarding Maintenance of Enzootic Variants of Yersinia pestis in Sylvatic Reservoirs and Their Significance in the Evolution of Epidemic Plague

    PubMed Central

    Brubaker, Robert R.

    2010-01-01

    Abstract 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°C in culture media containing Na+ but lacking added Ca2+. 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. PMID:20158336

  15. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague

    PubMed Central

    Sha, Jian; Rosenzweig, Jason A.; Kirtley, Michelle L.; van Lier, Christina J.; Fitts, Eric C.; Kozlova, Elena V.; Erova, Tatiana E.; Tiner, Bethany L.; Chopra, Ashok K.

    2012-01-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersina pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD50. Intranasal infection of mice with 15 LD50 of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24–72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy of

  16. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague.

    PubMed

    Sha, Jian; Rosenzweig, Jason A; Kirtley, Michelle L; van Lier, Christina J; Fitts, Eric C; Kozlova, Elena V; Erova, Tatiana E; Tiner, Bethany L; Chopra, Ashok K

    2013-02-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersinia pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD(50). Intranasal infection of mice with 15 LD(50) of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24-72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy

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

    PubMed

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

    2014-02-01

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

  18. The sex-selective impact of the Black Death and recurring plagues in the Southern Netherlands, 1349-1450.

    PubMed

    Curtis, Daniel R; Roosen, Joris

    2017-10-01

    Although recent work has begun to establish that early modern plagues had selective mortality effects, it was generally accepted that the initial outbreak of Black Death in 1347-52 was a "universal killer." Recent bioarchaeological work, however, has argued that the Black Death was also selective with regard to age and pre-plague health status. The issue of the Black Death's potential sex selectivity is less clear. Bioarchaeological research hypothesizes that sex-selection in mortality was possible during the initial Black Death outbreak, and we present evidence from historical sources to test this notion. To determine whether the Black Death and recurring plagues in the period 1349-1450 had a sex-selective mortality effect. We present a newly compiled database of mortality information taken from mortmain records in Hainaut, Belgium, in the period 1349-1450, which not only is an important new source of information on medieval mortality, but also allows for sex-disaggregation. We find that the Black Death period of 1349-51, as well as recurring plagues in the 100 years up to 1450, often had a sex-selective effect-killing more women than in "non-plague years." Although much research tends to suggest that men are more susceptible to a variety of diseases caused by bacteria, viruses and parasites, we cannot assume that the same direction of sex-selection in mortality applied to diseases in the distant past such as Second Pandemic plagues. While the exact reasons for the sex-selective effect of late-medieval plague are unclear in the absence of further data, we suggest that simple inequities between the sexes in exposure to the disease may not have been a key driver. © 2017 Wiley Periodicals, Inc.

  19. A review of recent literature on plague

    PubMed Central

    Pollitzer, R.

    1960-01-01

    In his comprehensive monograph on plague, published by WHO in 1954, Dr Pollitzer pointed out that despite the marked drop in the incidence of this disease in recent years, he considered it impossible for various reasons to be complacent about the situation. Since this monograph appeared, plague has shown a truly spectacular decrease, but in case this is partly the outcome of a natural periodicity of the infection, the author still feels that the disease ”should be given continued attention by those interested in global public health”. To this end he summarizes here the latest information on the subject, his review covering not only works published since 1954, but also some earlier literature (particularly from the USSR) which was not available to him at the time of preparation of his monograph. PMID:13736873

  20. Yersinia pestis--etiologic agent of plague.

    PubMed Central

    Perry, R D; Fetherston, J D

    1997-01-01

    Plague is a widespread zoonotic disease that is caused by Yersinia pestis and has had devastating effects on the human population throughout history. Disappearance of the disease is unlikely due to the wide range of mammalian hosts and their attendant fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes it to very different environmental conditions and has resulted in some novel traits facilitating transmission and infection. Studies characterizing virulence determinants of Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory systems controlling the expression of some of these virulence factors have proven quite complex. These areas of research have provide new insights into the host-parasite relationship. This review will update our present understanding of the history, etiology, epidemiology, clinical aspects, and public health issues of plague. PMID:8993858

  1. Aberdeen's plague epidemic of 1647-48.

    PubMed

    Jillings, K

    2010-08-01

    This article discusses the plague epidemic that broke out in Scotland in the mid 1640s, particularly its effects on the city of Aberdeen where it remained virulent from April 1647 until the end of the following year. Prevailing medical understandings of disease causation and transmission will be discussed, and it will be shown that governments attempted to restrict outbreaks in accordance with these beliefs. The spread of plague throughout Scotland from 1644 will be summarised, with the focus on the impact of the disease on Aberdeen in 1647-48. The surviving council registers and other primary sources will be used to show how the city's governors responded to the dual threat of miasma and contagion in well-established ways.

  2. The effects of plague on the distribution of property: Ivrea, Northern Italy 1630.

    PubMed

    Alfani, Guido

    2010-03-01

    The demographic effects of the epidemics of plague in Early Modern Europe and their economic consequences illuminate the evolution of property structures and of wealth distribution during and after a mortality crisis. An analysis of the high-quality data available for the Italian city of Ivrea at the time of the 1630 plague shows the exceptional resilience of property structures. Like the social structures of the period, property structures were able to recover quickly, informed as they were by the lessons learnt by trial and error by the patrician families of the late Middle Ages, whose patrimonies had been badly damaged by the Black Death. In a period of recurrent catastrophes that struck European populations during the Old Demographic Regime, apparently 'inegalitarian' institutions seem to have had long-term 'egalitarian' effects.

  3. The plague under Marcus Aurelius and the decline and fall of the Roman Empire.

    PubMed

    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.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    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.

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

    PubMed Central

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:25011940

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

    PubMed

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

    2012-01-01

    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.

  8. Molecular insights into the history of plague.

    PubMed

    Drancourt, Michel; Raoult, Didier

    2002-01-01

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

  9. Field efficacy trials with sylvatic plague vaccine

    USGS Publications Warehouse

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

    2017-01-01

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

  10. Bichat guidelines for the clinical management of plague and bioterrorism-related plague.

    PubMed

    Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, Jan; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

    2004-12-15

    Yersinia pestis appears to be a good candidate agent for a bioterrorist attack. The use of an aerosolised form of this agent could cause an explosive outbreak of primary plague pneumonia. The bacteria could be used also to infect the rodent population and then spread to humans. Most of the therapeutic guidelines suggest using gentamicin or streptomycin as first line therapy with ciprofloxacin as optional treatment. Persons who come in contact with patients with pneumonic plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin for 7 days. Prevention of human-to-human transmission via patients with plague pneumonia can be achieved by implementing standard isolation procedures until at least 4 days of antibiotic treatment have been administered. For the other clinical types of the disease, patients should be isolated for the first 48 hours after the initiation of treatment.

  11. Ecology and Geography of Plague Transmission Areas in Northeastern Brazil

    PubMed Central

    Giles, John; Peterson, A. Townsend; Almeida, Alzira

    2011-01-01

    Plague in Brazil is poorly known and now rarely seen, so studies of its ecology are difficult. We used ecological niche models of historical (1966-present) records of human plague cases across northeastern Brazil to assess hypotheses regarding environmental correlates of plague occurrences across the region. Results indicate that the apparently focal distribution of plague in northeastern Brazil is indeed discontinuous, and that the causes of the discontinuity are not necessarily only related to elevation—rather, a diversity of environmental dimensions correlate to presence of plague foci in the region. Perhaps most interesting is that suitable areas for plague show marked seasonal variation in photosynthetic mass, with peaks in April and May, suggesting links to particular land cover types. Next steps in this line of research will require more detailed and specific examination of reservoir ecology and natural history. PMID:21245925

  12. Ecology and geography of plague transmission areas in northeastern Brazil.

    PubMed

    Giles, John; Peterson, A Townsend; Almeida, Alzira

    2011-01-04

    Plague in Brazil is poorly known and now rarely seen, so studies of its ecology are difficult. We used ecological niche models of historical (1966-present) records of human plague cases across northeastern Brazil to assess hypotheses regarding environmental correlates of plague occurrences across the region. Results indicate that the apparently focal distribution of plague in northeastern Brazil is indeed discontinuous, and that the causes of the discontinuity are not necessarily only related to elevation-rather, a diversity of environmental dimensions correlate to presence of plague foci in the region. Perhaps most interesting is that suitable areas for plague show marked seasonal variation in photosynthetic mass, with peaks in April and May, suggesting links to particular land cover types. Next steps in this line of research will require more detailed and specific examination of reservoir ecology and natural history.

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

    PubMed Central

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

    2013-01-01

    ABSTRACT A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates. Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions. The ultimate extinction of plague pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments. PMID:23404402

  14. Potency of killed plague vaccines prepared from avirulent Yersinia pestis*

    PubMed Central

    Williams, James E.; Altieri, Patricia L.; Berman, Sanford; Lowenthal, Joseph P.; Cavanaugh, Dan C.

    1980-01-01

    Killed plague vaccines prepared from avirulent strains A1122 and EV76S of Yersinia pestis were more effective in mouse potency tests than samples of Plague Vaccine, USP, prepared from killed Y. pestis of the virulent strain 195/P. Manufacture of vaccine from avirulent Y. pestis would obviate requirements for the large containment facilities that are currently needed for producing Plague Vaccine, USP. PMID:6975184

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

    PubMed

    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.

  16. Disease Limits Populations: Plague and Black-Tailed Prairie Dogs

    PubMed Central

    Johnson, Tammi L.; Collinge, Sharon K.; Ray, Chris

    2010-01-01

    Abstract 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. PMID:20158327

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

    USGS Publications Warehouse

    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.

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

    PubMed

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

    2010-01-01

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

  19. Protecting against plague: towards a next-generation vaccine.

    PubMed

    Williamson, E D; Oyston, P C F

    2013-04-01

    The causative organism of plague is the bacterium Yersinia pestis. Advances in understanding the complex pathogenesis of plague infection have led to the identification of the F1- and V-antigens as key components of a next-generation vaccine for plague, which have the potential to be effective against all forms of the disease. Here we review the roles of F1- and V-antigens in the context of the range of virulence mechanisms deployed by Y. pestis, in order to develop a greater understanding of the protective immune responses required to protect against plague.

  20. Protecting against plague: towards a next-generation vaccine

    PubMed Central

    Williamson, E D; Oyston, P C F

    2013-01-01

    The causative organism of plague is the bacterium Yersinia pestis. Advances in understanding the complex pathogenesis of plague infection have led to the identification of the F1- and V-antigens as key components of a next-generation vaccine for plague, which have the potential to be effective against all forms of the disease. Here we review the roles of F1- and V-antigens in the context of the range of virulence mechanisms deployed by Y. pestis, in order to develop a greater understanding of the protective immune responses required to protect against plague. PMID:23480179

  1. Efficacy of the UK Recombinant Plague Vaccine to Protect Against Pneumonic Plague in the Nonhuman Primate, Macaca Fascicularis (PRIVATE)

    DTIC Science & Technology

    2004-05-05

    Alhydrogel. They were challenged on day 60 with a lethal aerosol challen survived. 2 1 INTRODUCTION Plague is an infection caused by the gram negative...Testing has been completed and shown Plague is an infection of small rodents and mammals - for example the ra popu ess. Plague has been responsible for...protective against challenge 28 of the immunization schedule through to week 53 after two compete with mpetitive ELISA. The competitive binding data

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

    PubMed Central

    Haseeb, MA

    2015-01-01

    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. PMID:26713244

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

    PubMed

    Wimsatt, Jeffrey; Biggins, Dean E

    2009-06-01

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

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

    PubMed Central

    Oyston, Petra C.F.; Williamson, Diane

    2011-01-01

    Simple Summary Plague is a notorious disease of humans, typically transmitted from rodents to man by the bite of infected fleas. However, plague can also be brought into the home by domestic animals. Cats are acutely susceptible to plague and can pose a significant hazard to close contacts. Dogs are relatively resistant to plague, but can import infected fleas into the home. This review discusses options available for vaccinating cats and dogs, to protect the animals, their owners and veterinarians from infection. Abstract 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. PMID:26486314

  5. Perceptions and reactions with regard to pneumonic plague.

    PubMed

    Rubin, G James; Amlot, Richard; Rogers, M Brooke; Hall, Ian; Leach, Steve; Simpson, John; Wessely, Simon

    2010-01-01

    We assessed perceptions and likely reactions of 1,005 UK adults to a hypothetical terrorist attack involving pneumonic plague. Likely compliance with official recommendations ranged from good (98% would take antimicrobial drugs) to poor (76% would visit a treatment center). Perceptions about plague were associated with these intentions.

  6. Perceptions and Reactions with Regard to Pneumonic Plague

    PubMed Central

    Amlôt, Richard; Rogers, M. Brooke; Hall, Ian; Leach, Steve; Simpson, John; Wessely, Simon

    2010-01-01

    We assessed perceptions and likely reactions of 1,005 UK adults to a hypothetical terrorist attack involving pneumonic plague. Likely compliance with official recommendations ranged from good (98% would take antimicrobial drugs) to poor (76% would visit a treatment center). Perceptions about plague were associated with these intentions. PMID:20031056

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

    PubMed

    Duffin, Christopher J

    2016-02-01

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

  8. Plague epizootic cycles in Central Asia

    PubMed Central

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

    2014-01-01

    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. PMID:24966205

  9. Plague epizootic cycles in Central Asia.

    PubMed

    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.

  10. Experimental plague infection in South African wild rodents.

    PubMed Central

    Shepherd, A. J.; Leman, P. A.; Hummitzsch, D. E.

    1986-01-01

    Susceptibility studies were undertaken to determine the response of some South African wild rodent species to experimental plague (Yersinia pestis) infection. A degree of plague resistance was found in three gerbil species captured in the plague enzootic region of the northern Cape Province, these being the Namaqua gerbil, Desmodillus auricularis, (LD50 1 X 10(6) organisms), the bushveld gerbil, Tatera leucogaster, (LD50 9.1 X 10(5)) and the highveld gerbil, T. brantsii (LD50 4 X 10(2)). Animals from a population of the four-striped mouse, Rhabdomys pumilio, captured in the plague area of Port Elizabeth, proved moderately resistant to experimental plague infection (LD50 1.3 X 10(4)) while those from another population of the same species captured in a plague-free area of the Orange Free State were extremely susceptible (LD50, 5 organisms). The response of both populations however was a heterogeneous one. Marked differences in susceptibility were also found between two populations of multimammate mice, Mastomys natalensis (2n = 32) although both originated from areas outwith the known distribution of plague in southern Africa. The 50% infectious dose was relatively high in T. leucogaster (3.2 X 10(2)) and D. auricularis (1.7 X 10(3)), but was low (2-16 organisms) in the other rodent species tested. The plague antibody response, determined by enzyme-linked immunosorbent assay (ELISA), was extremely short-lived in T. leucogaster, only 10% of inoculated animals remaining seropositive at low titres after 11 weeks. Antibodies persisted for only slightly longer in the sera of T. brantsii which were reinoculated with 2 X 10(3) plague organisms 6 weeks after initial challenge. The demonstration of the existence of both susceptible and resistant populations of R. pumilio and M. natalensis indicates that these species must be considered as potential plague reservoir hosts in parts of South Africa. The results suggest that resistance to plague infection in previously epizootic

  11. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    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."

  13. Hereditary hemochromatosis restores the virulence of plague vaccine strains.

    PubMed

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

    2012-10-01

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

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

    PubMed

    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.

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

    PubMed Central

    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

  16. Microbial Genomics of Ancient Plagues and Outbreaks.

    PubMed

    Andam, Cheryl P; Worby, Colin J; Chang, Qiuzhi; Campana, Michael G

    2016-12-01

    The recent use of next-generation sequencing methods to investigate historical disease outbreaks has provided us with an unprecedented ability to address important and long-standing questions in epidemiology, pathogen evolution, and human history. In this review, we present major findings that illustrate how microbial genomics has provided new insights into the nature and etiology of infectious diseases of historical importance, such as plague, tuberculosis, and leprosy. Sequenced isolates collected from archaeological remains also provide evidence for the timing of historical evolutionary events as well as geographic spread of these pathogens. Elucidating the genomic basis of virulence in historical diseases can provide relevant information on how we can effectively understand the emergence and re-emergence of infectious diseases today and in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Grácio, A. J. dos Santos

    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. PMID:28904964

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

    PubMed

    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.

  19. Interspecific comparisons of sylvatic plague in prairie dogs

    USGS Publications Warehouse

    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.

  20. Diagnosis of duck plague in waterfowl by polymerase chain reaction.

    PubMed

    Hansen, W R; Nashold, S W; Docherty, D E; Brown, S E; Knudson, D L

    2000-01-01

    A recently developed polymerase chain reaction (PCR) assay was used for diagnosis of duck plague in waterfowl tissues from past and current cases of waterfowl mortality and to identify duck plague virus in combined cloacal/oral-pharyngeal swab samples from healthy mallards (Anas platyrhynchos) after a disease outbreak. The PCR was able to detect viral DNA from all the individual or pooled tissues assayed from 10 waterfowl, including liver and spleen samples from three Muscovy ducks (Cairina moschata domesticus) that did not yield virus isolates. The strong staining intensity of the PCR products from the waterfowl tissues indicated that large amounts of virus were present, even when virus was not isolated. Duck plague DNA was also detected in a cloacal swab sample from a wood duck (Aix sponsa) carcass submitted for diagnosis. The PCR assay identified duck plague DNA in 13 swab samples that produced virus isolates from carrier mallards sampled in 1981 after a duck plague die-off. The duck plague PCR clearly demonstrated the ability to quickly diagnose duck plague in suspect mortality cases and to detect virus shed by carrier waterfowl.

  1. Diagnosis of duck plague in waterfowl by polymerase chain reaction

    USGS Publications Warehouse

    Hansen, W.R.; Nashold, S.W.; Docherty, D.E.; Brown, S.E.; Knudson, D.L.

    2000-01-01

    A recently developed polymerase chain reaction (PCR) assay was used for diagnosis of duck plague in waterfowl tissues from past and current cases of waterfowl mortality and to identify duck plague virus in combined cloacal/oral-pharyngeal swab samples from healthy mallards (Anas platyrhynchos) after a disease outbreak. The PCR was able to detect viral DNA from all the individual or pooled tissues assayed from 10 waterfowl, including liver and spleen samples from three Muscovy ducks (Cairina moschata domesticus) that did not yield virus isolates. The strong staining intensity of the PCR products from the waterfowl tissues indicated that large amounts of virus were present, even when virus was not isolated. Duck plague DNA was also detected in a cloacal swab sample from a wood duck (Aix sponsa) carcass submitted for diagnosis. The PCR assay identified duck plague DNA in 13 swab samples that produced virus isolates from carrier mallards sampled in 1981 after a duck plague die-off. The duck plague PCR clearly demonstrated the ability to quickly diagnose duck plague in suspect mortality cases and to detect virus shed by carrier waterfowl.

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

    PubMed

    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.

  3. Plague in Iran: its history and current status

    PubMed Central

    2016-01-01

    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. PMID:27457063

  4. Identification of duck plague virus by polymerase chain reaction.

    PubMed

    Hansen, W R; Brown, S 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 3' ends of an undefined open reading frame and the gene for DNA polymerase protein in other herpesviruses. Three of four primers 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.

  5. A solitary case of duck plague in a wild mallard

    USGS Publications Warehouse

    Wobeser, G.; Docherty, D.E.

    1987-01-01

    Duck plague was diagnosed on the basis of pathology and virus isolation in a wild female mallard Anas platyrhynchos found dead near Saskatoon, Saskatchewan. Day-old Pekin ducklings and one of two adult mallards died with lesions typical of duck plague following inoculation of tissue from the wild bird. This is believed to be the only reported case of duck plague in a wild bird since a major outbreak occurred in South Dakota in 1973, and the fourth such report in North America.

  6. [Sympatric Speciation of the Plague Microbe Yersinia pestis: Monohostal Specialization in the Host-Parasite Marmot-Flea (Marmota sibirica-Oropsylla silantiewi) System].

    PubMed

    Suntsov, V V

    2016-01-01

    An ecological scenario of the origin of the plague microbe that is interpreted in the light of modern Darwinism (synthetic theory of evolution) is presented. It is shown that the plague microbe emerged from a clone of the psychrophilic saprozoonotic pseudotuberculosis microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan time, 22000-15000 years ago, in the monohostal Mongolian marmot (Marmota sibirica)-flea (Oropsylla silantiewi) host-parasite system. It was noted that the evolutionary process described corresponds to the sympatric form of speciation by transition ofthe clone of migrant founders to a new, already-existing ecological niche. It was established that monohostal specialization of the plague microbe was made possible due to heterothermia (5-37 degrees C) of marmots in the hibernation period. The factors of the speciation process--isolation, the struggle for existence, and natural selection--were analyzed.

  7. [Regulations in the struggle against the plague. Geneva facing the Great Plague of Marseille (1720-1723)].

    PubMed

    Wenger, Alexandre

    2003-01-01

    In 1721, when Geneva is threatened by a terrible epidemic devastating the south of France, the physician Jean-Jaques Manget states that "The Magistrates must establish a good Policy in time of plague"; and asks himself how it is possible to carry on "without good Regulations?". The State Archives of Geneva hold a draft consisting of 72 articles concerning health policy meant to be applied in case of plague. This is a remarkable document that enables an overview of the city's organisation in times of plague; it also allows to analyse some of the medical and sanitary theories this organisation is based on.

  8. Understanding the persistence of plague foci in Madagascar.

    PubMed

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

    2013-11-01

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

  9. Plague in camels and its prevention in the USSR*

    PubMed Central

    Fedorov, V. N.

    1960-01-01

    In 1954-56 a series of experiments was carried out in Central Asia, under the guidance of the author, in which camels were infected with plague by infesting them with Ixodes and Argas ticks which had previously fed on plague-infected laboratory animals. Subcutaneous, intradermal and intravenous injection was also used. The experiments showed that the camels varied markedly in their susceptibility to plague, which in any case was relatively low. Special investigations on plague prevention in camels are also reported. Vaccination with dried live vaccine injected in a single dose of 30 000 million organisms created a sufficiently high degree of immunity in adult animals. Spraying of the camels' coats with insecticide is also recommended. PMID:13821869

  10. Plague in Arab Maghreb, 1940–2015: A Review

    PubMed Central

    Malek, Maliya Alia; Bitam, Idir; Drancourt, Michel

    2016-01-01

    We reviewed the epidemiology of 49 plague outbreaks that 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 harbors and transmitted by rat ectoparasites. By 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 Yersinia pestis from the Arab Maghreb. PMID:27376053

  11. Understanding the Persistence of Plague Foci in Madagascar

    PubMed Central

    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

  12. Sylvatic plague vaccine and management of prairie dogs

    USGS Publications Warehouse

    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

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

    PubMed

    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

  14. Bibliographic Index to the Plague (1965-1970)

    DTIC Science & Technology

    1975-11-18

    34). 346. Orlova, G. MI. and B. N. 𔃾ishan’kin, Dynamics of the frowth of the Plague Microbe and the Accumulation of Fraction I (C-psalar Antigen) in a...T. Voronina and L. 1. Kalmykova, The Effect of Iron on the Growth and Biological Properties of Vaccine Strain FV in Conditions of Aeration. Prot...I., The Ability of Plague Microbes to Accumulate Mouse Toxin Under Various Cultural Conditions. Prob. Dread Dis., Issue 2 (12), pp. 96- 99, 1970

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

    PubMed

    Langley, Eric

    2011-12-01

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

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

    USGS Publications Warehouse

    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 (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs 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.

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

    PubMed

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

    2012-02-01

    In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs were quite similar in their response, with overall survival rates of 50% and 60%, respectively. Prairie dogs from these states were heterogeneous 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.

  18. Resistance to Plague Among Black-Tailed Prairie Dog Populations

    PubMed Central

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

    2012-01-01

    Abstract 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 (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs 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. PMID:21923261

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

    USGS Publications Warehouse

    Rocke, T.E.; Williamson, J.; Cobble, K.R.; Busch, J.D.; Antolin, M.F.; Wagner, D.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 (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs 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. ?? 2012, Mary Ann Liebert, Inc.

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

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

  2. Duck plague: a carrier state in waterfowl.

    PubMed

    Burgess, E C; Ossa, J; Yuill, T M

    1979-01-01

    Healthy waterfowl were found to be carriers of duck plague (DP) virus. Black ducks (Anas rubripes) and Canada geese (Branta canadensis) surviving a natural outbreak of DP at Coloma, Wisconsin, in 1973 yielded DP virus in cloacal swabs taken four years postinfection. Experimental infection of previously unexposed mallard ducks (Anas platyrhynochos) with the Coloma strain of DP virus CO-WI (73) also produced cloacal virus shedding for up to four years after infection. A second DP virus strain, LA-SD (73) from the Lake Andes, South Dakota, epornitic, was detected from cloacal swabs of pintail ducks (Anas acuta), gadwall ducks (Anas strepera), wood ducks (Aix sponsa), and Canada geese infected experimentally one year before. The frequency of swabs positive for DP virus varied between individuals within each of the tested species. The amount of detectable DP virus shed was about 100 plaqueforming units of virus percloacal swab. Oral erosions were present in all species tested except Canada geese and gadwall ducks. Erosions occurred at the openings of the sublingual salivary gland ducts. DP virus was isolated from erosions. All ducks with lesions proved to shed DP virus, although not necessarily at the time they had the lesion.

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

    PubMed

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

    2013-10-31

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

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

    PubMed Central

    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

  5. The Venetian lazarettos of Candia and the Great Plague (1592 - 1595).

    PubMed

    Tsiamis, Costas; Thalassinou, Eleni; Poulakou-Rebelakou, Effie; Tsakris, Athanasios; Hatzakis, Angelos

    2014-03-01

    The present study highlights the history of lazarettos in Candia (modern Heraklion, Crete, Greece), which was the most important Venetian possession in the Mediterranean at the time, while at the same time it recounts the terrible plague which went down in history as the Great Plague of Candia (1592-1595). The study will also attempt to give a satisfactory answer to the epidemiological questions raised by the worst epidemic that Crete had experienced since the era of the Black Death in the 14th century. The city was about to lose more than a half of its population (51.3%), although it was saved from complete annihilation by the composure, courage and inventiveness of its Venetian commander, Filippo Pasqualigo, whose report to the Venetian Senate makes an invaluable source of information regarding the events of this dramatic period. Candia would also witness the emergence of typical human reactions in cases of epidemics and mass deaths, such as running away along with the feeling of self-preservation, dissolute life and ephemeral pleasures, as well as lawlessness and criminality. The lazaretto proved inefficient in the face of a disaster of such scale, whereas the epidemic functioned as a "crash-test" for the Venetian health system. Eventually, in an era when the microbial nature of the disease was unknown, it seems that it was practically impossible to handle emergency situations of large-scale epidemics successfully, despite strict laws and well-organized precautionary health systems.

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

    PubMed Central

    de Almeida, Alzira Maria Paiva; Cordeiro-Estrela, Pedro

    2016-01-01

    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. PMID:27711205

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

    PubMed

    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.

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

    PubMed

    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. Population decline and plague in late medieval Norway.

    PubMed

    Brothen, J A

    1996-01-01

    Norwegian scholars have engaged in considerable research over the last half century in an attempt to assess the impact of the Black Plague of 1349 on population and society in Norway. Evidence has been put forward relating the incidence of plague to a continuance of population decline over the two centuries following its initial introduction. Estimates of population decline in Norway between 1350 and 1550 indicate a reduction by as much as 65%. Two directions of study have emerged, one concentrating on land abandonment known as the "Ødegard Project." The other is represented by the recent works of Ole Jørgen Benedictow presenting epidemiological and osteo-archaeological research. An examination of the available literature raises questions concerning the degree to which plague, and its recurrence, directly affected population decline in Norway during the Late Middle Ages. While evidence of the virulence of the plague and the degree of farm abandonment is compelling, a direct relationship to population decline may not be as great as implied by the research. Other explanatory factors, especially social and economic responses to plague, have been given limited attention.

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

    PubMed

    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.

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

    PubMed

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

    2008-12-01

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

  12. Plague in camels and goats: their role in human epidemics.

    PubMed

    Christie, A B; Chen, T H; Elberg, S S

    1980-06-01

    In 1976, in a small, remote Libyan village, one apparently sick camel was slaughtered and skinned, and the camel meat was distributed for human comsumption. A few days later, 15 villagers suffered a severe febrile illness. Of the five individuals who had participated in the killing and dispensation of the camel, all were dead within four days. When samples of serum from nine of the remaining patients were examined, seven were found to be positive for plague as determined by the passive hemagglutination test. Another six persons became ill after killing two goats, and the serum of one goat contained antibodies to Yersinia pestis. Because all of the remaining patients except one were treated early enough, they recovered. These incidents confirm previous reports that the camel and the goat are susceptible to naturally occurring plague infection and have a significant role in the dissemination of human plague.

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

    PubMed

    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

    2014-04-07

    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.

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

    PubMed Central

    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

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

    PubMed

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

    2016-01-01

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

  16. A victory over the plague in Moscow 1770-1772.

    PubMed

    Sorokina, Tatiana

    2013-06-01

    The Great Plague in Moscow 1770-1772 was suppressed in four months due to the strict and effective administrative measures and outstanding efforts of the doctors in Moscow. For many decades of the previous century the role of the Russian nobility in this victory was "forgotten". In this paper, based on the original documents published just after the Plague in 1775, a real historical picture of that Great Victory has been reconstructed. Many errors and inaccuracies in our historical-medical literature have been corrected and the forgotten role of the Russian nobility in suppressing this serious epidemic has been resurrected. This includes the role of the Senate, the Empress Catherine the Great and Count Gregory Orlov who had been sent by her to Moscow with unlimited power "to put everything in due order", as well as contribution of the Russian scientists in the worldwide struggle against plague.

  17. Reflections on crisis burials related to past plague epidemics.

    PubMed

    Signoli, M

    2012-03-01

    Drawing its etymology from the Latin pestis (curse), plague, over the centuries, has been more dreaded by humankind than any other epidemic. The Apocalypse had recognized plague as the archetypal divine curse, 'the power to kill over a fourth of the earth'. Plague is thus a particular topic of study, insofar that it is one of the rare epidemics that has had recurrent major consequences on demography and human societies. Its highly transmissible nature, the brutality of its action, its high pathogenicity, marked by strong lethality and great swiftness, and the complete absence of treatment options before the 20th century conferred on it a sinister aspect. Generating a series of severe demographic crises, well known in the Western world, it has necessarily influenced the evolution of societies at both the biological and cultural levels. © 2012 The Author. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    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.

  20. Assessment of the immune response to duck plague vaccinations.

    PubMed

    Kulkarni, D D; James, P C; Sulochana, S

    1998-01-01

    An experiment was conducted to assess the immune responses of ducks to duck plague (DP) vaccinations employing one commercial and one laboratory-adapted (LA) DP vaccines. Virus neutralisation and leucocyte migration-inhibition tests were conducted at regular intervals before and after vaccinations. Similarly, ducks in vaccinated and control groups were subjected to challenge infection with virulent DP virus. The commercial vaccine yielded a poor immune response and partial protection on challenge whereas satisfactory responses were obtained in ducks receiving two doses of LA vaccine. The humoral as well as cellular factors were stimulated indicating possible involvement of both the immune responses in the protection from duck plague.

  1. [Establishment of the plague control system in Russia].

    PubMed

    Onishchenko, G G; Monisov, A A; Fedorov, Iu M; Kutyrev, V V; Kokushkin, A M

    1999-01-01

    The specialized plague control facilities which began being founded as a system of institutions in Russia in 1897 have made a great contribution to epidemiological well-being against quarantine and particularly menacing diseases. The developmental stages of plague control service in different periods of the country's social life and its place in the general governmental preventive and antiepidemic measures are shown. The paper emphasizes that it is expedient to maintain the antiepidemic readiness of plaque control facilities due the fact that the epidemic situation is due menacing and zoonosis is expected to aggravate in the late 20th to the early 21st centuries.

  2. [The plague of the third pandemic and its current remergence].

    PubMed

    Barry, Stéphane

    2008-12-01

    The reappearance of the plague in the 19th century, in what is generally referred to as the third pandemic, brought back painful memories of the great plague outbreaks of the past that had killed tens of millions of people. At the same time, this new pandemic opened the era of great discoveries, such as identification of the Yersinia pestis bacterium, of transmission vectors and the first effective treatments. With these advances it became possible to control a disease which had, because of progress in maritime transport, spread almost throughout the world.

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

    PubMed

    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.

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

    PubMed

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

    2010-06-01

    In Madagascar, the black rat, Rattus rattus, is the main reservoir of plague (Yersinia pestis infection), a disease still responsible for hundreds of cases each year in this country. This study used experimental plague challenge to assess susceptibility in wild-caught rats to better understand how R. rattus can act as a plague reservoir. An important difference in plague resistance between rat populations from the plague focus (central highlands) and those from the plague-free zone (low altitude area) was confirmed to be a widespread phenomenon. In rats from the plague focus, we observed that sex influenced plague susceptibility, with males slightly more resistant than females. Other individual factors investigated (weight and habitat of sampling) did not affect plague resistance. When infected at high bacterial dose (more than 10⁵ bacteria injected), rats from the plague focus died mainly within 3-5 days and produced specific antibodies, whereas after low-dose infection (< 5,000 bacteria), delayed mortality was observed and surviving seronegative rats were not uncommon. These results concerning plague resistance level and the course of infection in the black rat would contribute to a better understanding of plague circulation in Madagascar.

  5. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    SciTech Connect

    Goldberg, D.R.; Yuill, T.M.; Burgess, E.C. )

    1990-07-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  6. Plague Vaccine Development: Current Research and Future Trends

    PubMed Central

    Verma, Shailendra Kumar; Tuteja, Urmil

    2016-01-01

    Plague is one of the world’s most lethal human diseases caused by Yersinia pestis, a Gram-negative bacterium. Despite overwhelming studies for many years worldwide, there is no safe and effective vaccine against this fatal disease. Inhalation of Y. pestis bacilli causes pneumonic plague, a fast growing and deadly dangerous disease. F1/LcrV-based vaccines failed to provide adequate protection in African green monkey model in spite of providing protection in mice and cynomolgus macaques. There is still no explanation for this inconsistent efficacy, and scientists leg behind to search reliable correlate assays for immune protection. These paucities are the main barriers to improve the effectiveness of plague vaccine. In the present scenario, one has to pay special attention to elicit strong cellular immune response in developing a next-generation vaccine against plague. Here, we review the scientific contributions and existing progress in developing subunit vaccines, the role of molecular adjuvants; DNA vaccines; live delivery platforms; and attenuated vaccines developed to counteract virulent strains of Y. pestis. PMID:28018363

  7. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    USGS Publications Warehouse

    Goldberg, D.R.; Yuill, Thomas M.; Burgess, E.C.

    1990-01-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  8. Changing Socioeconomic Indicators of Human Plague, New Mexico, USA

    PubMed Central

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

    2012-01-01

    Socioeconomic indicators associated with temporal changes in the distribution of human plague cases in New Mexico were investigated for 1976–2007. In the 1980s, cases were more likely in census block groups with poor housing conditions, but by the 2000s, cases were associated with affluent areas concentrated in the Santa Fe–Albuquerque region. PMID:22709463

  9. Changing socioeconomic indicators of human plague, New Mexico, USA.

    PubMed

    Schotthoefer, Anna M; Eisen, Rebecca J; Kugeler, Kiersten J; Ettestad, Paul; Reynolds, Pamela J; Brown, Ted; Enscore, Russell E; Cheek, James; Bueno, Rudy; Targhetta, Joseph; Montenieri, John A; Gage, Kenneth L

    2012-07-01

    Socioeconomic indicators associated with temporal changes in the distribution of human plague cases in New Mexico were investigated for 1976-2007. In the 1980s, cases were more likely in census block groups with poor housing conditions, but by the 2000s, cases were associated with affluent areas concentrated in the Santa Fe-Albuquerque region.

  10. Empirical assessment of a threshold model for sylvatic plague.

    PubMed

    Davis, S; Leirs, H; Viljugrein, H; Stenseth, N Chr; De Bruyn, L; Klassovskiy, N; Ageyev, V; Begon, M

    2007-08-22

    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 using additional data from the same archives. Throughout the focus, population levels above the threshold were a necessary condition for an epizootic to occur. However, there were large numbers of occasions when an epizootic was not observed even though great gerbils were, and had been, abundant. We 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 was unfavourable, and (vi) a high proportion of gerbils were resistant. Of these, separate thresholds, fleas and climate received some support but accounted for few false positives and can be disregarded as serious omissions from the model. Small sample size and local extinction received strong support and can account for most of the false positives. Host resistance received no support here but should be subject to more direct experimental testing.

  11. Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

    PubMed Central

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

    2011-01-01

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

  12. Pathogenicity of duck plague and innate immune responses of the Cherry Valley ducks to duck plague virus.

    PubMed

    Li, Ning; Hong, Tianqi; Li, Rong; Guo, Mengjiao; Wang, Yao; Zhang, Jinzhou; Liu, Jiyuan; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2016-08-24

    Duck plague caused by duck plague virus (DPV) is an acute and contagious disease. To better understand the pathogenic mechanism of duck plague virus in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DPV could replicate quickly in many tissues, leading to pathological lesions, especially on the spleen. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the brain, and the antiviral innate immune response was established, but not sufficient to restrict viral replication. In contrast, although the expression of many major pattern recognition receptors (PRRs) increased in the spleen, the expression of most cytokines was declined. Our study indicates that DPV is a pantropic virus that can replicate rapidly in tissues, causing serious pathological lesions but the immune responses are different in the spleen and brain. To our knowledge, this is the first report to systematically explore the expression profiles of the immune genes in the DPV-infected ducks. Our data provide a foundation for further study of the pathogenicity of duck plague.

  13. [The Antonine Plague and the decline of the Roman Empire].

    PubMed

    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

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

    PubMed

    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

  15. Genotyping of Global Yersinia Pestis Isolates by Using IS285

    DTIC Science & Technology

    2006-11-01

    National Laboratory, Livermore, CA 94550-9234 ABSTRACT Yersinia pestis is the etiologic agent of bubonic and pneumonic plague , one of the most...1989: Plague Microbiology, Manual, Irkutsk State University, Irkutsk, USSR. Barreto, A., Aragon, M. and Epstein, P.R., 1995: Bubonic Plague ...Chanteau, S., 2002: Epidemiologic Features of Four Successive Annual Outbreaks of Bubonic Plague in Mahajanga, Madagascar, Emerg. Infect. Dis., 8, 311

  16. Plague, pox and the physician in Aberdeen, 1495-1516.

    PubMed

    Jillings, K

    2010-03-01

    This article discusses responses to disease in Aberdeen during a formative period in the provision of healthcare within the city. The foundation of King's College was followed, in 1497, by the establishment of the first royally endowed university Chair of Medicine in the British Isles, and its first incumbent, James Cumming, was employed by the local government as the first city doctor in 1503. His appointment had been preceded in 1497 by another legislative innovation in Aberdeen, when its council became the first civic body in the British Isles to implement regulations against the threat of the Great Pox (usually considered to be syphilis). It had subsequently to pass measures to prevent the spread of plague to the city, and these were typical of those already imposed elsewhere in Scotland and on the continent. Their apparent success in staving off plague lasted until 1514, when the city was struck by a severe outbreak which lasted two years.

  17. [Use of nested PCR in detection of the plague pathogen].

    PubMed

    Glukhov, A I; Gordeev, S A; Al'tshuler, M L; Zykova, I E; Severin, S E

    2003-07-01

    Causative agents of plague, i.e. bacterium Yersina pestis (in the subcutaneous tissues of rodents) and their cutaneous parasites need to be isolated to enable plague prevention. A comparatively new method of polymerase chain reaction (PCR) opens up new possibilities of determining Y. pestis just within several hours and without any cultivation. The article contains a description of the PCR-method, which makes it possible to distinguish the culture of Y. pestis from cultures of other microorganism, including speci of Yersina. The method is of the cluster-type, i.e. it is made up of subsequent PC reactions with the substrate for the second reaction being the product of the first one. The cluster nature of the method preconditions a higher sensitivity and specificity versus the ordinary PCR.

  18. Sylvatic plague vaccine: A new tool for conservation of threatened and endangered species?

    USGS Publications Warehouse

    Abbott, Rachel C.; Osorio, Jorge E.; Bunck, Christine M.; Rocke, Tonie E.

    2012-01-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  19. Sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?

    PubMed

    Abbott, Rachel C; Osorio, Jorge E; Bunck, Christine M; Rocke, Tonie E

    2012-09-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  20. Common Avian Infection Plagued the Tyrant Dinosaurs

    PubMed Central

    Wolff, Ewan D. S.; Salisbury, Steven W.; Horner, John R.; Varricchio, David J.

    2009-01-01

    Background Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name ‘Sue’) has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids. Methodology/Principal Findings We conducted an extensive survey of tyrannosaurid specimens and identified ten individuals with full-thickness erosive lesions. These lesions were described, measured and photographed for comparison with one another. We also conducted an extensive survey of related archosaurs for similar lesions. We show here that these lesions are consistent with those caused by an avian parasitic infection called trichomonosis, which causes similar abnormalities on the mandible of modern birds, in particular raptors. Conclusions/Significance This finding represents the first evidence for the ancient evolutionary origin of an avian transmissible disease in non-avian theropod dinosaurs. It also provides a valuable insight into the palaeobiology of these now extinct animals. Based on the frequency with which these lesions occur, we hypothesize that tyrannosaurids were commonly infected by a Trichomonas gallinae-like protozoan. For tyrannosaurid populations, the only non-avian dinosaur group that show trichomonosis-type lesions, it is likely that the disease became endemic and spread as a result of antagonistic intraspecific behavior, consumption of prey infected by a Trichomonas gallinae-like protozoan and possibly even cannibalism. The severity of trichomonosis-related lesions in specimens such as Tyrannosaurus rex FMNH PR2081 and Tyrannosaurus rex MOR 980, strongly suggests that these animals died as a direct result of this disease, mostly likely through starvation. PMID:19789646

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

    USGS Publications Warehouse

    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. A non-stationary relationship between global climate phenomena and human plague incidence in Madagascar.

    PubMed

    Kreppel, Katharina S; Caminade, Cyril; Telfer, Sandra; Rajerison, Minoarison; Rahalison, Lila; Morse, Andy; Baylis, Matthew

    2014-10-01

    Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar. We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation. This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.

  3. A Non-Stationary Relationship between Global Climate Phenomena and Human Plague Incidence in Madagascar

    PubMed Central

    Kreppel, Katharina S.; Caminade, Cyril; Telfer, Sandra; Rajerison, Minoarison; Rahalison, Lila; Morse, Andy; Baylis, Matthew

    2014-01-01

    Background Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar. Methodology/principal findings We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation. Conclusions/significance This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar. PMID

  4. Modern thermoelectrochemistry.

    PubMed

    Gründler, Peter; Kirbs, Andreas; Dunsch, Lothar

    2009-08-03

    Thermoelectrochemistry as a branch of electrochemistry like photoelectrochemistry is reviewed in an integral treatment of the subject. Especially modern thermoelectrochemistry is focused on new techniques to vary the temperature as an independent variable. This review based on a definition of modern thermoelectrochemistry includes all the classical work which contributes to the formation of modern thermoelectrochemistry, among them high-temperature electrochemistry, subcritical- and supercritical electrochemistry and in-situ electrochemical calorimetry. The main focus is on modern techniques like fast electrode heating by lasers or by alternating current as well as on heating of solution spots by microwaves and related methods. Here the state of the art in modern thermoelectrochemistry is critically reviewed for the first time.

  5. Microevolution and History of the Plague Bacillus, Yersinia pestis

    DTIC Science & Technology

    2007-11-02

    recognized by the three methods, and we propose an evolutionary tree for these populations, rooted on Yersinia pseudotuberculosis. The tree in- vokes...were recognized by the three methods, and we propose an evolutionary tree for these populations, rooted on Yersinia pseudotuberculosis. The tree invokes...Microevolution and history of the plague bacillus, Yersinia pestis Mark Achtman*†, Giovanna Morelli*, Peixuan Zhu*‡, Thierry Wirth*§, Ines Diehl

  6. Enhancing the Immune Response to Recombinant Plague Antigens

    DTIC Science & Technology

    2007-05-01

    CONTRACT NUMBER Enhancing the Immune Response to Recombinant Plague Antigens 5b. GRANT NUMBER DAMD17-02-2-0058 5c. PROGRAM ELEMENT NUMBER 6...mally integrated copy of the Bacillus anthracis protective antigen gene protects mice against an anthrax spore challenge. Infect Im- mun 2003;71(7):3831...multiplying the empirically determined aerosol exposure concentration (CFU/liter air) in the chamber by the amount of air that was estimated to have been

  7. Ancient Egyptian doctors and the nature of the biblical plagues.

    PubMed

    Trevisanato, Siro Igino

    2005-01-01

    Paragraph 55 of the London Medical Papyrus describes burns derived from red waters and which later became infected with larvae in the wounds. The prescribed treatment for the burn is unusual as it calls for no rinsing and requires bandaging with alkaline materials only. Refraining from washing in the Nile (the single most readily available source of water in ancient Egypt), and the use of alkali-neutralizing agents indicates that the red caustic waters came from the river, and were acid in nature. A red, acid Nile is consistent with the first biblical plague of Egypt, which killed fish, and kept people from drinking from the river. In turn, the sulfate-laced waters of the medical document also offer a plausible insight into the subsequent biblical plagues. Amphibians would have stayed away from the deadly river, left to die on the banks, just as described in the second biblical plague. Similarly, the larvae in the wounds mentioned by the medical document re-echo the third and fourth biblical plagues: the kînnîm invertebrates and the subsequent 'arob (varied insects) are consistent with larvae and the subsequent adults thereof. In pre-industrial Ancient Egypt, sulfates from a massive volcanic fall out provide the simplest and most exhaustive origin for such waters. A massive precipitation that would account for the waters in the medical document and the biblical texts is known from sediments at the bottom of lakes along the Nile Delta. The site is downwind from the island of Santorini, and the deposit of volcanic ashes took place during the Middle Bronze Age, i.e. at a time consistent with the eruption at the Greek volcanic island.

  8. Privet is a plague: You can help stop it

    Treesearch

    James H. Miller; Tim Albritton

    2004-01-01

    Have you noticed how privet appears to be exploding across the landscape? Privet is that rampant small-leaved shrub that stays green in winter and can be seen along many fencerows and forest edges, as well as invading interior forests. What at one time was considered the staple farm house shrub is now completely out of control. It has become a plague. In fact, it is...

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Plague: the dreadful visitation occupying the human mind for centuries.

    PubMed

    Khan, Iqbal Akhtar

    2004-05-01

    Plague is one of mankind's greatest scourges, which has swept away millions of people over the centuries. The first available record of the occurrence of this calamity, in humans, is from the Bible, in 1000 bc, in the city of Ashdod. The first definitely identified pandemic originated in Egypt in ad 542 (the Justinian Plague) and is estimated to have caused 100 million deaths. The second one, lasting for three centuries and claiming over 25 million lives appeared in 1334 in China spreading to many spots on the globe. The third pandemic occurred in Europe from the fifteenth to eighteenth century. The current pandemic began around 1860, in the Chinese province Yunnan; it reached Hong Kong in 1894 killing 100 000 individuals. Within 20 years the disease spread from southern Chinese ports throughout the world resulting in more than 10 million deaths. Since the discovery of the causative agent in 1894, there have been remarkable advancements in immunoprophylaxis and chemoprophylaxis. However, the disease is still active in Africa, in Asia and in Americas and has been classified as a currently re-emerging disease. A 'Plague-free World' will probably remain a dream for an indefinite period.

  11. Plague foci in Viet Nam: zoological and parasitological aspects.

    PubMed

    Suntsov, V V; Huong, L T; Suntsova, N I; Gratz, N G

    1997-01-01

    Reported are the results of studies over the period 1989-94 on host-flea complexes in small mammals and their flea ectoparasites in and around a number of human settlements in Viet Nam in which human cases of plague had been found. Collections were also made in savanna and tropical forest areas within a 10-km radius of the settlements. The greatest numbers of small mammals, for the most part Rattus spp., and of the flea ectoparasite Xenopsylla cheopis were found in inhabited areas. X. cheopis was not found on any feral or sylvan mammal further than 0.6 km from settlements. A possible link between wild and commensal mammals may be provided by the flea Lentistivalius klossi, a specific parasite of squirrels and tree-shrews but also found in very small numbers on commensal rats. No zoonotic foci of plague were found in the immediate vicinity of the villages studied and it is most likely that plague persists in a commensal rat-X. cheopis cycle in and around human settlements in Viet Nam.

  12. The Eleventh Plague: The Politics of Biological and Chemical Warfare

    NASA Astrophysics Data System (ADS)

    Kovac, Jeffrey

    1997-07-01

    Leonard A. Cole. W. H. Freeman: New York, 1997. 250 pp. ISBN 0-7167-2950-4. $22.95 hc. The Eleventh Plague begins with a recitation of the ten plagues brought down upon Egypt, part of the Passover Seder celebrated each spring by Jews all over the world. Spring is also the anniversary of the first use of chemical weapons. On April 22, 1915, German soldiers released chlorine gas from 5,739 cylinders installed along the battle line at Ypres in southeastern Belgium. Germany achieved complete surprise. The gas drifted across no man's land, causing widespread terror and creating ten thousand serious casualties and five thousand deaths. Chlorine, of course, was a poor weapon, easily neutralized, but German scientists, including future Nobel laureates Fritz Haber, Otto Hahn, and James Franck, and the German chemical industry created ever more dangerous chemical weapons, culminating with the introduction of mustard gas in 1917. Despite cries of moral outrage, the Allies countered with their own chemical weapons efforts. The eleventh plague had been unleashed.

  13. The concept of quarantine in history: from plague to SARS.

    PubMed

    Gensini, Gian Franco; Yacoub, Magdi H; Conti, Andrea A

    2004-11-01

    The concept of 'quarantine' is embedded in health practices, attracting heightened interest during episodes of epidemics. The term is strictly related to plague and dates back to 1377, when the Rector of the seaport of Ragusa (then belonging to the Venetian Republic) officially issued a 30-day isolation period for ships, that became 40 days for land travellers. During the next 100 years similar laws were introduced in Italian and in French ports, and they gradually acquired other connotations with respect to their original implementation. Measures analogous to those employed against the plague have been adopted to fight against the disease termed the Great White Plague, i.e. tuberculosis, and in recent times various countries have set up official entities for the identification and control of infections. Even more recently (2003) the proposal of the constitution of a new European monitoring, regulatory and research institution has been made, since the already available system of surveillance has found an enormous challenge in the global emergency of the severe acute respiratory syndrome (SARS). In the absence of a targeted vaccine, general preventive interventions have to be relied upon, including high healthcare surveillance and public information. Quarantine has, therefore, had a rebound of celebrity and updated evidence strongly suggests that its basic concept is still fully valid.

  14. India's Modern Slaves: Bonded Labor in India and Methods of Intervention

    ERIC Educational Resources Information Center

    Boutros, Heidi

    2005-01-01

    Slavery flourishes in the modern world. In nations plagued by debilitating poverty, individuals unable to afford food, clothing, and shelter may be compelled to make a devastating decision: to sell themselves or their children into slavery. Nowhere in the world is this more common than India. Conservative estimates suggest that there are 10…

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

    PubMed Central

    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

  16. Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

    PubMed

    Salkeld, Daniel J

    2017-09-06

    The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

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

    PubMed

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

    2012-05-22

    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.

  18. Identification of duck plague virus by polymerase chain reaction

    USGS Publications Warehouse

    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

  19. Enzootic Plague Reduces Black-Footed Ferret (Mustela nigripes) Survival in Montana

    DTIC Science & Technology

    2010-01-01

    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...and probably trans- mission, of plague at enzootic levels. Other studies have demonstrated similar effects of flea control on several species of...2006a). Plague is a major obstacle to recovery of endangered ferrets, and epizootics have an easily noticed and dramatic effect, especially on black

  20. Rodent and Flea Abundance Fail to Predict a Plague Epizootic in Black-Tailed Prairie Dogs

    PubMed Central

    Collinge, Sharon K.; Ray, Chris; Gage, Ken L.

    2010-01-01

    Abstract Small rodents are purported to be enzootic hosts of Yersinia pestis and may serve as sources of infection to prairie dogs or other epizootic hosts by direct or flea-mediated transmission. Recent research has shown that small rodent species composition and small rodent flea assemblages are influenced by the presence of prairie dogs, with higher relative abundance of both small rodents and fleas at prairie dog colony sites compared to grasslands without prairie dogs. However, it is unclear if increased rodent or flea abundance predisposes prairie dogs to infection with Y. pestis. We tracked rodent and flea occurrence for 3 years at a number of prairie dog colony sites in Boulder County, Colorado, before, during, and after a local plague epizootic to see if high rodent or flea abundance was associated with plague-affected colonies when compared to colonies that escaped infection. We found no difference in preepizootic rodent abundance or flea prevalence or abundance between plague-positive and plague-negative colonies. Further, we saw no significant before-plague/after-plague change in these metrics at either plague-positive or plague-negative sites. We did, however, find that small rodent species assemblages changed in the year following prairie dog die-offs at plague-affected colonies when compared to unaffected colonies. In light of previous research from this system that has shown that landscape features and proximity to recently plagued colonies are significant predictors of plague occurrence in prairie dogs, we suggest that landscape context is more important to local plague occurrence than are characteristics of rodent or flea species assemblages. PMID:20158331

  1. Rodent and flea abundance fail to predict a plague epizootic in black-tailed prairie dogs.

    PubMed

    Brinkerhoff, Robert Jory; Collinge, Sharon K; Ray, Chris; Gage, Ken L

    2010-01-01

    Small rodents are purported to be enzootic hosts of Yersinia pestis and may serve as sources of infection to prairie dogs or other epizootic hosts by direct or flea-mediated transmission. Recent research has shown that small rodent species composition and small rodent flea assemblages are influenced by the presence of prairie dogs, with higher relative abundance of both small rodents and fleas at prairie dog colony sites compared to grasslands without prairie dogs. However, it is unclear if increased rodent or flea abundance predisposes prairie dogs to infection with Y. pestis. We tracked rodent and flea occurrence for 3 years at a number of prairie dog colony sites in Boulder County, Colorado, before, during, and after a local plague epizootic to see if high rodent or flea abundance was associated with plague-affected colonies when compared to colonies that escaped infection. We found no difference in preepizootic rodent abundance or flea prevalence or abundance between plague-positive and plague-negative colonies. Further, we saw no significant before-plague/after-plague change in these metrics at either plague-positive or plague-negative sites. We did, however, find that small rodent species assemblages changed in the year following prairie dog die-offs at plague-affected colonies when compared to unaffected colonies. In light of previous research from this system that has shown that landscape features and proximity to recently plagued colonies are significant predictors of plague occurrence in prairie dogs, we suggest that landscape context is more important to local plague occurrence than are characteristics of rodent or flea species assemblages.

  2. Primary plague pneumonia contracted from a domestic cat at South Lake Tahoe, Calif.

    PubMed

    Werner, S B; Weidmer, C E; Nelson, B C; Nygaard, G S; Goethals, R M; Poland, J D

    1984-02-17

    Primary plague pneumonia occurred in a 47-year-old South Lake Tahoe woman shortly after face-to-face exposure to her plague pneumonia-infected cat. Both died. Field investigation revealed a recent plague epizootic in squirrels and chipmunks around the patient's home. Control measures included active surveillance and chemoprophylaxis of 197 contacts to the victim, a community alert on methods of self- and pet protection, and application of insecticide to reduce rodent flea populations. No secondary cases occurred.

  3. Modernity's Prometheus.

    ERIC Educational Resources Information Center

    Morris, Richard

    1993-01-01

    Argues for reframing and reforging the relationship between text and context. Argues that the silences that modernity's tribute to text invites are grotesque, untenable, and fundamentally anti-intellectual. (SR)

  4. Modernity's Prometheus.

    ERIC Educational Resources Information Center

    Morris, Richard

    1993-01-01

    Argues for reframing and reforging the relationship between text and context. Argues that the silences that modernity's tribute to text invites are grotesque, untenable, and fundamentally anti-intellectual. (SR)

  5. Landscape ecology of plague in the American southwest, September 19-20, 2000, Fort Collins, Colorado

    USGS Publications Warehouse

    Brand, Christopher J.

    2002-01-01

    During September 19-20, 2000, a workshop titled "Landscape Ecology of Plague in the American Southwest" was held in Fort Collins, Colorado. The workshop was funded by the U.S. Geological Survey (USGS)-Earth Surface Processes Team and sponsored by the USGS National Wildlife Health Center. Forty scientists and natural resource managers and administrators representing 8 federal agencies, 4 state agencies, 6 universities, and other local agencies and nongovernment organizations met to discuss historical and current status of plague in the United States, current activities in plague surveillance, research, and management in wildlife, and research and information needs relative to plague control and management. Eleven individual presentations on plague history, status, and trends; diagnostic technologies; epizootiological studies and observations; and control and management strategies and studies, followed by a panel discussion on the impact of plague on wildlife and ecosystems, led the way to extensive group discussions on important plague-related questions, issues and problems. Workshop attendees participated in identifying important research and information needs relevant to control and management of plague in wildlife, and in the process, established new cooperative and collaborative partnerships and enhanced existing relationships upon which future research and information needs can be met. The proceedings from this workshop are intended to be used by the natural resource managers and researchers from the various participating agencies, research facilities, as well as other stakeholders to aid in the development of future research and information programs and funding initiatives related to both zoonotic and sylvatic plague.

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

    PubMed Central

    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

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

    PubMed

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

    2011-06-21

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

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

    PubMed Central

    Lewnard, Joseph A.

    2016-01-01

    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. PMID:27791071

  9. [Thomas Montanus, author of the plague treatise, Qualitas loimodea sive pestis Brugana: some biographical data].

    PubMed

    Van Laere, J

    1999-01-01

    Thomas Montanus (1617-1685), physician of the City of Bruges, is the author of a voluminous treatise on plague, published in 1669, and written after an epidemic of plague in Bruges in 1666. A translation in Dutch of the treatise will be published shortly. In this contribution some biographical data on Montanus are presented: his descendence, his education, his career and his professional experience with plague. On the other hand the structure of the plague treatise Qualitas loimodea sive pestis Brugana is briefly mentioned.

  10. Recombinant raccoon pox vaccine protects mice against lethal plague

    USGS Publications Warehouse

    Osorio, J.E.; Powell, T.D.; Frank, R.S.; Moss, K.; Haanes, E.J.; Smith, S.R.; Rocke, T.E.; Stinchcomb, D.T.

    2003-01-01

    Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7??104LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague. ?? 2002 Elsevier Science Ltd. All rights reserved.

  11. AFLP genome scan in the black rat (Rattus rattus) from Madagascar: detecting genetic markers undergoing plague-mediated selection.

    PubMed

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

    2011-03-01

    The black rat (Rattus rattus) is the main reservoir of plague (Yersinia pestis infection) in Madagascar's rural zones. Black rats are highly resistant to plague within the plague focus (central highland), whereas they are susceptible where the disease is absent (low altitude zone). To better understand plague wildlife circulation and host evolution in response to a highly virulent pathogen, we attempted to determine genetic markers associated with plague resistance in this species. To this purpose, we combined a population genomics approach and an association study, both performed on 249 AFLP markers, in Malagasy R. rattus. Simulated distributions of genetic differentiation were compared to observed data in four independent pairs, each consisting of one population from the plague focus and one from the plague-free zone. We found 22 loci (9% of 249) with higher differentiation in at least two independent population pairs or with combining P-values over the four pairs significant. Among the 22 outlier loci, 16 presented significant association with plague zone (plague focus vs. plague-free zone). Population genetic structure inferred from outlier loci was structured by plague zone, whereas the neutral loci dataset revealed structure by geography (eastern vs. western populations). A phenotype association study revealed that two of the 22 loci were significantly associated with differentiation between dying and surviving rats following experimental plague challenge. The 22 outlier loci identified in this study may undergo plague selective pressure either directly or more probably indirectly due to hitchhiking with selected loci. © 2010 Blackwell Publishing Ltd.

  12. Relationship between oriental migratory locust plague and soil moisture extracted from MODIS data

    NASA Astrophysics Data System (ADS)

    Liu, Zhenbo; Shi, Xuezheng; Warner, Eric; Ge, Yunjian; Yu, Dongsheng; Ni, Shaoxiang; Wang, Hongjie

    2008-02-01

    Locust plagues have been the source of some of the most severe natural disasters in human history. Soil moisture content is among the most important of the numerous factors influencing plague onset and severity. This paper describes a study initiated in three pilot locust plague monitoring regions, i.e., Huangzao, Yangguanzhuang, and Tengnan in Huanghua county, Hebei province, China, to examine the impact of soil moisture status on oriental migratory locust [ Locusta migratoria manilensis (L.) Meyen] plague breakout as related to the life cycle, oviposition in autumn, survival in winter, and incubation in summer. Thirty-nine temperature vegetation dryness index (TVDI) data sets, which represent soil moisture content, were extracted from MODIS remote sensing images for two representative time periods: a severe locust plague breakout year (2001-2002) and a slight plague year (2003-2004). TVDI values demonstrated distinctive soil moisture status differences between the 2 years concerned. Soil moisture conditions in the severe plague year were shown to be lower than those in slight plague year. In all three pilot regions, average TVDI value in the severe plague year was 0.07 higher than that in slight plague year, and monthly TVDI values in locust oviposition period (September and October) and incubation period (March, April and May) were higher than their corresponding monthly figures in slight plague year. No remarkable TVDI differences were found in other months during the locust life cycle between the 2 years. TVDI values for September and October (2001), March, April and May (2002) were 0.11, 0.08, 0.16, 0.11 and 0.16 higher than their corresponding monthly figures in 2003-2004 period, respectively.

  13. The plague of Athens: an ancient act of bioterrorism?

    PubMed

    Papagrigorakis, Manolis J; Synodinos, Philippos N; Stathi, Angeliki; Skevaki, Chrysanthi L; Zachariadou, Levantia

    2013-09-01

    Recent data implicate Salmonella enterica serovar Typhi as a causative pathogen of the Plague of Athens during the Peloponnesian War (430-426 bc). According to Thucydides, the sudden outbreak of the disease may link to poisoning of the water reservoirs by the Spartans. The siege of a city was aimed at exhausting the supplies of a population, which often led to the outbreak and spread of epidemics. Poisoning of the water reservoirs of a besieged city as an act of bioterrorism would probably shorten the necessary time for such conditions to appear.

  14. Assessing plague risk and presence through surveys of small mammal flea communities

    Treesearch

    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)....

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

    USGS Publications Warehouse

    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.

  16. Response of mountain plovers to plague-driven dynamics of black-tailed prairie dog colonies

    USDA-ARS?s Scientific Manuscript database

    Sylvatic plague is a major factor influencing prairie dog colony dynamics in the western Great Plains. We studied the nesting response of the mountain plover (Charadrius montanus), a grassland bird that nests on prairie dog colonies, to plague-driven dynamics of prairie dog colonies at three sites i...

  17. Population genetic structure of the prairie dog flea and plague vector, Oropsylla hirsuta.

    PubMed

    Brinkerhoff, R Jory; Martin, Andrew P; Jones, Ryan T; Collinge, Sharon K

    2011-01-01

    Oropsylla hirsuta is the primary flea of the black-tailed prairie dog and is a vector of the plague bacterium, Yersinia pestis. We examined the population genetic structure of O. hirsuta fleas collected from 11 prairie dog colonies, 7 of which had experienced a plague-associated die-off in 1994. In a sample of 332 O. hirsuta collected from 226 host individuals, we detected 24 unique haplotype sequences in a 480 nucleotide segment of the cytochrome oxidase II gene. We found significant overall population structure but we did not detect a signal of isolation by distance, suggesting that O. hirsuta may be able to disperse relatively quickly at the scale of this study. All 7 colonies that were recently decimated by plague showed signs of recent population expansion, whereas 3 of the 4 plague-negative colonies showed haplotype patterns consistent with stable populations. These results suggest that O. hirsuta populations are affected by plague-induced prairie dog die-offs and that flea dispersal among prairie dog colonies may not be dependent exclusively on dispersal of prairie dogs. Re-colonization following plague events from plague-free refugia may allow for rapid flea population expansion following plague epizootics.

  18. A plague epizootic in the black-tailed prairie dog (Cynomys ludovicianus).

    PubMed

    Pauli, Jonathan N; Buskirk, Steven W; Williams, Elizabeth S; Edwards, William H

    2006-01-01

    Plague is the primary cause for the rangewide decline in prairie dog (Cynomys spp.) distribution and abundance, yet our knowledge of plague dynamics in prairie dog populations is limited. Our understanding of the effects of plague on the most widespread species, the black-tailed prairie dog (C. ludovicianus), is particularly weak. During a study on the population biology of black-tailed prairie dogs in Wyoming, USA, plague was detected in a colony under intensive monitoring, providing a unique opportunity to quantify various consequences of plague. The epizootic reduced juvenile abundance by 96% and adult abundance by 95%. Of the survivors, eight of nine adults and one of eight juveniles developed antibodies to Yersinia pestis. Demographic groups appeared equally susceptible to infection, and age structure was unaffected. Survivors occupied three small coteries and exhibited improved body condition, but increased flea infestation compared to a neighboring, uninfected colony. Black-tailed prairie dogs are capable of surviving a plague epizootic and reorganizing into apparently functional coteries. Surviving prairie dogs may be critical in the repopulation of plague-decimated colonies and, ultimately, the evolution of plague resistance.

  19. Modern Spectroscopy

    ERIC Educational Resources Information Center

    Barrow, Gordon M.

    1970-01-01

    Presents the basic ideas of modern spectroscopy. Both the angular momenta and wave-nature approaches to the determination of energy level patterns for atomic and molecular systems are discussed. The interpretation of spectra, based on atomic and molecular models, is considered. (LC)

  20. Duck plague epizootics in the United States, 1967-1995

    USGS Publications Warehouse

    Converse, K.A.; Kidd, Gregory A.

    2001-01-01

    In 1967, the first confirmed diagnosis of duck plague (DP) in the USA was made from pekin ducks (Anas platyrhynchos domesticus) on commercial duck farms on Long Island, New York. Within 10 mo, DP was confirmed as the cause of death in migratory waterfowl on a Long Island bay. This paper reviews 120 DP epizootics reported from 1967 to 1995 that involved waterfowl species native to North America or were reported in areas with free-flying waterfowl at risk. Duck plague epizootics occurred in 21 states with the greatest number reported in Maryland (29), New York (18), California (16), and Pennsylvania (13). The greatest frequency of epizootics (86%) was detected during the months of March to June. At least 40 waterfowl species were affected with the highest frequency of epizootics reported in captive or captive-reared ducks including muscovy ducks (Cairina moschata) (68%), mallard ducks (A. platyrhynchos) (18%) and black ducks (A. rubripes) (14%). The greatest number of waterfowl died in three epizootics that involved primarily migratory birds in 1967 and 1994 in New York (USA) and 1973 in South Dakota (USA). The greatest number of DP epizootics reported since 1967 appear to have involved flocks of non-migratory rather than migratory waterfowl; therefore, in our opinion it remains unknown if DP is enzootic in either non-migratory or migratory waterfowl.

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

    PubMed

    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.

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

    PubMed Central

    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

  3. Knowledge, attitudes and public health response towards plague in Petauke, Zambia.

    PubMed

    Ngulube, T J; Mwanza, K; Njobvu, C A; Muula, A S

    2006-10-01

    In 2001, two plague outbreaks were reported in Zambia, one of which occurred in Petauke, Eastern Province, resulting in high morbidity and mortality. Of the community respondents, 43.4% did not know the aetiology of plague. Although rats and fleas were frequently mentioned, many respondents did not know how these were related to plague. Local belief that the plague outbreak was the result of witchcraft was prevalent. Use of rodenticides was not preferred as these were reports of they being used for poisoning people. The public health response was initially slow by both the community and also the formal health sector. Once the diagnosis of plague was made, fears of witchcraft dispelled and collaboration not only between the formal health sector and the community, but also between Zambian health workers and their Mozambican counterparts developed, and it was possible to control the outbreak.

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

    PubMed

    Schmid, Boris V; Büntgen, Ulf; Easterday, W Ryan; Ginzler, Christian; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr

    2015-03-10

    The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

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

    PubMed

    Bos, Kirsten I; Herbig, Alexander; Sahl, Jason; Waglechner, Nicholas; Fourment, Mathieu; Forrest, Stephen A; Klunk, Jennifer; Schuenemann, Verena J; Poinar, Debi; Kuch, Melanie; Golding, G Brian; Dutour, Olivier; Keim, Paul; Wagner, David M; Holmes, Edward C; Krause, Johannes; Poinar, Hendrik N

    2016-01-21

    The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague's persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.

  6. Globalism of Outbreak and Prevalence of Cattle Plague(Rinderpest) around Byengjahoran (1636-1638).

    PubMed

    Kim, Dong Jin; Yoo, Han Sang

    2013-04-01

    This study reviewed the outbreak and prevalence of cattle plague around Byeongjahoran from the perspective of international war in East Asia. First of all, the epidemiological characteristics of cattle plague in Manchuria where the outbreak of cattle plague was first reported around Byeongjahoran were analyzed. From the study, it was found the military activities that Sarhu (Qing) had made during the growth into Empire promoted the exchanges of various germs which became naturalized in the regions in Northeast Asia, and that such extreme situation as war made various diseases taken place and dispersed. In particular, because of military activities of Sarhu (Qing), various contagious diseases including smallpox which was prevalent in Inner-Mongolia and Shanxi became prevalent in Manchuria. During the contacts with Chosun after Jeongmyohoran, pathogen occurring Rinderpest was introduced into Manchuria. Favorable conditions for the interactions with various pathogens were provided by frequent contacts with wild animals through hunting and various cultivation groups composed of Manchurians, Mongolians, Han-Chinese and Chosun people. Rinderpest breaking in Chosun around Byeongjahoran was originated in Shenyang in 1636. It was transmitted to cattle in the Korean Peninsula and expanded to Kansai Region. At that time Rinderpest occurred and rapidly expanded in a specific area due to the interactions of pathogens, hosts and environments, and suddenly disappeared because of the extinction and the separation of hosts. It is consistent with the symptoms of modern times 'Rinderpest.' In Chosun it occurred in Pyeongan-do 4 months before the outbreak of Byeongjahoran and gave great damage on the capital area and northern Gyeonggi region. Because of the large scale migration of militaries after Byeongjahoran, Rindpest was expanded to Hasamdo and was terminated in February to April leaving big damages. The damages of Byeongjahoran were very severe. From the statistical records, it

  7. Current Trends in Plague Research: From Genomics to Virulence

    PubMed Central

    Huang, Xiao-Zhe; Nikolich, Mikeljon P.; Lindler, Luther E.

    2006-01-01

    Yersinia pestis is the causative agent of plague, which diverged from Yersinia pseudotuberculosis within the past 20,000 years.Although these two species share a high degree of homology at the DNA level (>90%), they differ radically in their pathogenicity and transmission. In this review, we briefly outline the known virulence factors that differentiate these two species and emphasize genetic studies that have been conducted comparing Y. pestis and Y. pseudotuberculosis.These comparisons have led to a better understanding of the genetic contributions to the differences in the virulence and pathogenicity between these two organisms and have generated information that can be applied in future diagnostic and vaccine development. Comparison of the genetic differences between Y. pestis and Y. pseudotuberculosis has also lent insight into the emergence of acute pathogens from organisms causing milder diseases. PMID:16988099

  8. Origin of the Old Testament Plagues: Explications and Implications

    PubMed Central

    Ehrenkranz, N. Joel; Sampson, Deborah A.

    2008-01-01

    Analyses of past disasters may supply insights to mitigate the impact of recurrences. In this context, we offer a unifying causative theory of Old Testament plagues, which has present day public health implications. We propose the root cause to have been an aberrant El Niño-Southern Oscillation teleconnection that brought unseasonable and progressive climate warming along the ancient Mediterranean littoral, including the coast of biblical Egypt, which, in turn, initiated the serial catastrophes of biblical sequence — in particular arthropod-borne and arthropod-caused diseases. Located beyond the boundary of focal climate change, inland Goshen would not have been similarly affected. Implicit in this analysis is a framework to consider a possibility of present day recurrence of similar catastrophes and their impact upon essential public services. PMID:18604309

  9. Origin of the old testament plagues: explications and implications.

    PubMed

    Ehrenkranz, N Joel; Sampson, Deborah A

    2008-03-01

    Analyses of past disasters may supply insights to mitigate the impact of recurrences. In this context, we offer a unifying causative theory of Old Testament plagues, which has present day public health implications. We propose the root cause to have been an aberrant El Niño-Southern Oscillation teleconnection that brought unseasonable and progressive climate warming along the ancient Mediterranean littoral, including the coast of biblical Egypt, which, in turn, initiated the serial catastrophes of biblical sequence - in particular arthropod-borne and arthropod-caused diseases. Located beyond the boundary of focal climate change, inland Goshen would not have been similarly affected. Implicit in this analysis is a framework to consider a possibility of present day recurrence of similar catastrophes and their impact upon essential public services.

  10. [Transylvanian refugees and the plague in 1708-1709].

    PubMed

    Kis, D

    1993-01-01

    Owing to the overwhelming military power of the Habsburg forces Transylvanian sympathizers fled twice to Hungary during the Rákóczi uprising (1704-1711): first in 1704-1706 and then in 1707-1711. In the autumn of 1707 they numbered as much as ten thousand people, and according to the decrees of the diet at Kisvárda, they were settled down in smaller units in around Szabolcs, Szatmár, Bereg, Ung, Ugocsa and Máramaros counties. Though always short of money, the leaders of the ukprising created a system that satisfied the basic needs of these refugees. By the end of the rebellion, nevertheless, as the territory controlled by Rákóczi's armies decreased considerably, the refugees were forced to move on and on, which certainly led to a corruption of their food supplies, accommodation and hygienic conditions. The worst among all came with the plague. The author examines the effects of the epidemic and the counter-measures taken by the individual and the authorities of the uprising. Kis has consulted the main Hungarian books of that age that referred to black death (among others Anna Zay's Herbarium [1719], Samuel Köleséri's Pestis Daicae, György Komáromi Csipkés's Pestis pestise, Ferenc Pápai Páriz's Pax Corporis and A [estos betegség etc., and Máté Tsanaki's A Döghalálról, etc.), as well as many archival papers (the correspondence of Count Sándor Károlyi with his wife Krisztina Barkóczy, thos of General Bercsényi to his wife and Prince Rákóczi, and some doctors' reports, etc.). His main source, however, is Zsigmond Szaniszló's diary. Szaniszló was a former fobiró (chief-sheriff) of the Transsylvanian Torda city, an Anti-Trinitarian stronghold, and remained a leader of his people during the emigration. According to his notes, which the author has compared with the data given by the others, there were hardly any measures taken against plague in this community. Although Szaniszló gives detailed descriptions about the everyday life of the

  11. Burrow dusting or oral vaccination prevents plague-associated prairie dog colony collapse

    USGS Publications Warehouse

    Tripp, Daniel W.; Rocke, Tonie E.; Runge, Jonathan P.; Abbott, Rachel C.; Miller, Michael W.

    2017-01-01

    Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant “sylvatic plague vaccine” [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots (“blocks”) receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P < 0.0001), and prairie dogs captured on dust plots had fewer fleas (P < 0.0001) than those on vaccine or placebo plots. Burrow activity and prairie dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

  12. Influence of human activity patterns on epidemiology of plague in Western Usambara Mountains, Tanzania.

    PubMed

    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.

  13. Plague outbreaks in prairie dog populations explained by percolation thresholds of alternate host abundance

    PubMed Central

    Salkeld, Daniel J.; Salathé, Marcel; Stapp, Paul; Jones, James Holland

    2010-01-01

    Highly lethal pathogens (e.g., hantaviruses, hendra virus, anthrax, or plague) pose unique public-health problems, because they seem to periodically flare into outbreaks before disappearing into long quiescent phases. A key element to their possible control and eradication is being able to understand where they persist in the latent phase and how to identify the conditions that result in sporadic epidemics or epizootics. In American grasslands, plague, caused by Yersinia pestis, exemplifies this quiescent–outbreak pattern, because it sporadically erupts in epizootics that decimate prairie dog (Cynomys ludovicianus) colonies, yet the causes of outbreaks and mechanisms for interepizootic persistence of this disease are poorly understood. Using field data on prairie community ecology, flea behavior, and plague-transmission biology, we find that plague can persist in prairie-dog colonies for prolonged periods, because host movement is highly spatially constrained. The abundance of an alternate host for disease vectors, the grasshopper mouse (Onychomys leucogaster), drives plague outbreaks by increasing the connectivity of the prairie dog hosts and therefore, permitting percolation of the disease throughout the primary host population. These results offer an alternative perspective on plague's ecology (i.e., disease transmission exacerbated by alternative hosts) and may have ramifications for plague dynamics in Asia and Africa, where a single main host has traditionally been considered to drive Yersinia ecology. Furthermore, abundance thresholds of alternate hosts may be a key phenomenon determining outbreaks of disease in many multihost-disease systems. PMID:20660742

  14. Burrow Dusting or Oral Vaccination Prevents Plague-Associated Prairie Dog Colony Collapse.

    PubMed

    Tripp, Daniel W; Rocke, Tonie E; Runge, Jonathan P; Abbott, Rachel C; Miller, Michael W

    2017-06-22

    Plague impacts prairie dogs (Cynomys spp.), the endangered black-footed ferret (Mustela nigripes) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant "sylvatic plague vaccine" [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog (C. ludovicianus) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots ("blocks") receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow (P < 0.0001), and prairie dogs captured on dust plots had fewer fleas (P < 0.0001) than those on vaccine or placebo plots. Burrow activity and prairie dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

  15. The history of the plague and the research on the causative agent Yersinia pestis.

    PubMed

    Zietz, Björn P; Dunkelberg, Hartmut

    2004-02-01

    The plague is an infectious bacterial disease having a high fatality rate without treatment. It has occurred in three huge pandemics since the 6th century with millions of deaths and numerous smaller epidemics and sporadic cases. Referring to specific clinical symptoms of pulmonary plague the disease became known as the Black Death. This pandemic probably originated in central Asia and began spreading westward along major trade routes. Upon the arrival in the eastern Mediterranean the disease quickly spread especially by sea traffic to Italy, Greece and France and later throughout Europe by land. Until the 18th century many European cities were frequently affected by other great plague epidemics. The worldwide spread of the third pandemic began when the plague reached Hong Kong and Canton in the year 1894. The gram-negative coccobacillus now designated as Yersinia pestis has been discovered as the causative agent of plague in this Hong Kong outbreak. In the following years the role of rats and fleas and their detailed role in the transmission of plague has been discovered and experimentally verified. Today the plague is still endemic in many countries of the world.

  16. A bibliography of literature pertaining to plague (Yersinia pestis)

    USGS Publications Warehouse

    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.

  17. [PLAGUE IN PALERMO IN 1575 AND SOCIAL CONTROL].

    PubMed

    Malta, Renato; Salerno, Alfredo

    2015-01-01

    The work moves from the low mortality of the plague of Palermo in 1575 - 1576 in comparison to similar outbreaks and contemporary analysis of the activity of Ingrassia, a man that the city government had wanted at his side. The extraordinary health interventions, including those to favor of the predisposition of health building to isolation, gears for a more wide-ranging than the traditional one. The isolation adopted by Ingrassia wasn't a novelty because it was already in use half a century earlier, as the Previdelli wrote. We assume that the population in crisis, hungry and out of work for the huge military expenditure of king Philip II, would have prompted the City government to use the outbreak for the purposes of . At the same goal always answered in the sixteenth century the establishment of the parish, created to divide the territory in order to guide and control the practice of the faith of the people. Ingrassia, a man next to political power, which in turn welded with the spiritual power in order to implement the Catholic Counter-Reformation, justified the coercive initiatives towards the population. The practice of medicine, as still happens today, is affected by the conditions of the policy, raising one of the fundamental principles of bioethics, the question ofthe independence ofthe doctor: a physician divided by the duty to represent the legitimate interests of the patient and those of political power, perhaps not always shared. It is a new interpretation of the activity of Ingrassia and his results than the plague.

  18. Milestones in Progression of Primary Pneumonic Plague in Cynomolgus Macaques▿

    PubMed Central

    Koster, Frederick; Perlin, David S.; Park, Steven; Brasel, Trevor; Gigliotti, Andrew; Barr, Edward; Myers, Leslie; Layton, Robert C.; Sherwood, Robert; Lyons, C. R.

    2010-01-01

    Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (Macaca fascicularis) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of Yersinia pestis strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a Yersinia 16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1β, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines. PMID:20385751

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26123398

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

    PubMed Central

    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

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

    PubMed

    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.

  3. Landscape structure and plague occurrence in black-tailed prairie dogs on grasslands of the western USA

    USGS Publications Warehouse

    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

    Landscape structure influences the abundance and distribution of many species, including pathogens that cause infectious diseases. Black-tailed prairie dogs in the western USA have declined precipitously over the past 100 years, most recently due to grassland conversion and their susceptibility to sylvatic plague. We assembled and analyzed two long-term data sets on plague occurrence in black-tailed prairie dogs to explore the hypotheses that plague occurrence is associated with colony characteristics and landscape context. Our two study areas (Boulder County, Colorado, and Phillips County, Montana) differed markedly in degree of urbanization and other landscape characteristics. In both study areas, we found associations between plague occurrence and landscape and colony characteristics such as the amount of roads, streams and lakes surrounding a prairie dog colony, the area covered by the colony and its neighbors, and the distance to the nearest plague-positive colony. Logistic regression models were similar between the two study areas, with the best models predicting positive effects of proximity to plague-positive colonies and negative effects of road, stream and lake cover on plague occurrence. Taken together, these results suggest that roads, streams and lakes may serve as barriers to plague in black-tailed prairie dog colonies by affecting movement of or habitat quality for plague hosts or for fleas that serve as vectors for the pathogen. The similarity in plague correlates between urban and rural study areas suggests that the correlates of plague are not altered by uniquely urban stressors. ?? Springer 2005.

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

    PubMed Central

    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

  5. The anti-plague system and the Soviet biological warfare program.

    PubMed

    Zilinskas, Raymond A

    2006-01-01

    The USSR possessed a unique national public health system that included an agency named "anti-plague system." Its mission was to protect the country from highly dangerous diseases of either natural or laboratory etiology. During the 1960s, the anti-plague system became the lead agency of a program to defend against biological warfare, codenamed Project 5. This responsibility grew and by the middle 1970s came to include undertaking tasks for the offensive biological warfare program, codenamed Ferment. This article describes the anti-plague system's activities relevant to both aspects of the Soviet Union's biological warfare program, offense and defense, and analyzes its contributions to each.

  6. Feline plague in New Mexico: risk factors and transmission to humans.

    PubMed Central

    Eidson, M; Tierney, L A; Rollag, O J; Becker, T; Brown, T; Hull, H F

    1988-01-01

    The epidemiologic features of 60 cases of feline plague from 1977-1985 in New Mexico are reviewed. The most frequent clinical presentation was lethargy, anorexia, fever, and enlarged lymph nodes or abscesses. A history of hunting rodents was reported in 75 per cent of all cases. Five human plague cases were associated with five feline cases. Recommendations are presented for prevention of plague infection and transmission to humans, including restraining cats from roaming and hunting by neutering and keeping them indoors, treating them for fleas, and seeking medical care for febrile illnesses, especially when accompanied by enlarged lymph nodes. PMID:3421391

  7. Quinto Tiberio Angelerio and new measures for controlling plague in 16th-century Alghero, Sardinia.

    PubMed

    Bianucci, Raffaella; 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.

  8. [Rate of formation of postvaccinal immunity to plague in animal experiments].

    PubMed

    Chicherin, Iu V; Evstigneev, V I; Lebedinskiĭ, V A

    1977-04-01

    The authors present the results of experimental studies on guinea pigs of the dynamics of plague immunity formation after a single inhalation immunization of the animals with live plague vaccine. Plague immunity proved to develop as soon as 24 hours after the application of the preparation; by the 3rd day the resistance level was 68 times greater than the control one. Immunity reached the maximal intensity by the 20th day after the vaccination. The level of specific resistance decreased 1.6 by the 3rd month.

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

    PubMed

    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. Plague in Egypt: Disease biology, history and contemporary analysis: A minireview

    PubMed Central

    Lotfy, Wael M.

    2013-01-01

    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. PMID:26199744

  11. [Efficacy of cefixime and cefepime vs. other cephalosporins in experimental plague of albino mice due to variants FI+ and FI- of the plague microbe].

    PubMed

    Ryzhko, I V; Shcherbaniuk, A I; Moldavan, I A; Tsuraeva, R I; Anisimov, B I; Trishina, A V

    2007-01-01

    Efficacy of cefixime and cefepime vs. ceftriaxone, cefotaxime, ceftazidime and cefoperazone was studied in vitro and in the treatment of experimental plague of albino mice due to natural, antigen complete strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsule antigen fraction I (FI- phenotype). The MICs of cefixime and cefepime for 20 FI+ and 20 FI- strains of the plague microbe were 0.02-0.08 mg/l, that corresponded to the MICs of ceftriaxone, cefotaxime and ceftazidime. The MICs of cefoperazone were somewhat higher (0.1-0.2 mg/l). The ED50 values of cefixime and cefepime for prevention and treatment of experimental plague in mice statistically did not significantly differ from the ED50 values of ceftriaxone, cefotaxime, ceftazidime and cefoperazone. The efficacy indices (EIs) of cefixime and cefepime were > 10(4) independent of the infective strain phenotype (FI+ or FI-) and did not differ from those of ceftriaxone and ceftazidime. The efficacy of cefotaxime and cefoperazone was somewhat lower (EIs 1.7 x 10(3)-8.9 x 10(3)). Both the antibacterials were shown to provide high protective and therapeutic efficacy (80-100% of the survivors) independent of the phenotype (FI+ or FI-) of the pathogen infective strain. The results allowed to consider the antibiotics prospective in prevention and treatment of plague.

  12. No evidence of deer mouse involvement in plague (Yersinia pestis) epizootics in prairie dogs.

    PubMed

    Salkeld, Daniel J; Stapp, Paul

    2008-06-01

    Plague, the disease caused by the bacterium Yersinia pestis, can have devastating impacts on black-tailed prairie dog (Cynomys ludovicianus) colonies. One suggested mechanism behind sporadic prairie dog die-offs involves an alternative mammal host, such as the deer mouse (Peromyscus maniculatus), which often inhabits prairie dog colonies. We examined the flea populations of deer mice to investigate the potential of flea-borne transmission of plague between deer mice and prairie dogs in northern Colorado, where plague is active in prairie dog colonies. Deer mice were predominantly infested with the flea Aetheca wagneri, and were rarely infested with prairie dog fleas, Oropsylla hirsuta. Likelihood of flea infestation increased with average monthly temperature, and flea loads were higher in reproductive animals. These results suggest that the deer mouse is an unlikely maintenance host of plague in this region.

  13. [Change in the habitat of Yersinia pestis in the Gorno-Altaisk natural focus of plague].

    PubMed

    Korzun, V M; Chipanin, E V; Balakhonov, S V; Denisov, A V; Rozhdestvenskiĭ, E N; Mihaĭlov, E P; Iarygina, M B; Kosilko, S A

    2014-01-01

    The paper analyzes the change that occurred in the habitat of the causative agent of plague in its Gorno-Altaisk natural focus in 1961 to 2012. Since 1961 when the plague microbe was found to come from the southern slopes of the Saylyugem mountain range, which are located in Mongolia, to the northern slopes situated in Russia, a gradual expansion of the habitat of Yersenia pestis subsp. altaica had commenced in South-Eastern Altai. During the considered period, the area where epizootic manifestations were registered showed an 11-fold increase. In most cases, the spread of the plague pathogen within the focus was natural and occurred in the successive and closely related settlements of Mongolian pikas (Ochotona pallasi). By now, the plague microbe has been widely distributed in three populations of this small animal, which inhabit the territory of South-Eastern Altai.

  14. Plague metapopulation dynamics in a natural reservoir: the burrow system as the unit of study.

    PubMed

    Davis, S; Klassovskiy, N; Ageyev, V; Suleimenov, B; Atshabar, B; Klassovskaya, A; Bennett, M; Leirs, H; Begon, M

    2007-07-01

    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, it is useful to consider the burrow system as the unit of study within a much larger metapopulation.

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

    PubMed

    Laayouni, Hafid; Oosting, Marije; Luisi, Pierre; Ioana, Mihai; Alonso, Santos; Ricaño-Ponce, Isis; Trynka, Gosia; Zhernakova, Alexandra; Plantinga, Theo S; Cheng, Shih-Chin; van der Meer, Jos W M; Popp, Radu; Sood, Ajit; Thelma, B K; Wijmenga, Cisca; Joosten, Leo A B; Bertranpetit, Jaume; Netea, Mihai G

    2014-02-18

    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 history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1β, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis-induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment.

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

    PubMed Central

    Laayouni, Hafid; Oosting, Marije; Luisi, Pierre; Ioana, Mihai; Alonso, Santos; Ricaño-Ponce, Isis; Trynka, Gosia; Zhernakova, Alexandra; Plantinga, Theo S.; Cheng, Shih-Chin; van der Meer, Jos W. M.; Popp, Radu; Sood, Ajit; Thelma, B. K.; Wijmenga, Cisca; Joosten, Leo A. B.; Bertranpetit, Jaume; Netea, Mihai 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 history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1β, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis–induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment. PMID:24550294

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

    DTIC Science & Technology

    2012-09-01

    saliva are highest. The initial viraemia, which develops on the third and fourth day, is asymptomatic as the virus migrates to the spleen, bone marrow...namely anthrax (caused by Bacillus anthracis), plague (caused by Yersinia pestis) and smallpox (caused by variola virus ) that are often considered...Bacillus anthracis) and two contagious diseases, plague (caused by Yersinia pestis) and smallpox (caused by variola virus ). This approach will allow for

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

    PubMed Central

    Loya, Yossi; Stone, Lewi

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    Infectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatio-temporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347-1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10 km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river. This association remained robust in different regression model specifications. An increase of 100 m in the width of river and a shortening of 1 km distance between city and river resulted in 9 and 0.96 more plague outbreaks in our study period, respectively. Such relationship shows a declining trend over our study period due to the expansion of city and technological advancement in overland transportation. This study elucidates the key role of navigable river in the dissemination of plague in historical Europe.

  1. A Field Study of Plague and Tularemia in Rodents, Western Iran.

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

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

  3. Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    Infectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatio-temporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347–1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10 km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river. This association remained robust in different regression model specifications. An increase of 100 m in the width of river and a shortening of 1 km distance between city and river resulted in 9 and 0.96 more plague outbreaks in our study period, respectively. Such relationship shows a declining trend over our study period due to the expansion of city and technological advancement in overland transportation. This study elucidates the key role of navigable river in the dissemination of plague in historical Europe. PMID:27721393

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

    NASA Astrophysics Data System (ADS)

    Pak Hong, Y. R.

    2016-12-01

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

  7. [The North African plague and Charles Nicolle's theory of infectious diseases].

    PubMed

    Ben, Néfissa Kmar; Moulin, Anne Marie

    2010-01-01

    Many infectious diseases were described in North Africa in 18th-19th centuries by European travellers. Most of them were allegedly imported by new migrant populations coming from sub-Saharan, European or Middle East countries. Plague outbreaks have been described since the Black Death as diseases of the Mediterranean harbours. Charles Nicolle and his collaborators at the Pasteur Institute were witnesses to the extinction of plague and typhus fever in Tunisia. Both could be considered as endemo-epidemic diseases propagated by ancient nomad communities for centuries. Typhus was exported to other countries; plague was imported by Mediterranean travellers but also hid in unknown wild-animal reservoirs. The role of the bite of a rat's flea was not confirmed and the pneumonic form might have prevailed in the medieval North African cities. Association between plague, typhus, flu and other causes of immune deficiencies could explain the high morbidity and mortality caused by plague in the past. The authors comment the local history of plague at the light of the evolutionary laws of infectious disease proposed by Charles Nicolle in 1930.

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

    PubMed

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

    2008-02-01

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

  9. Flea abundance on black-tailed prairie dogs (Cynomys ludovicianus) increases during plague epizootics.

    PubMed

    Tripp, Daniel W; Gage, Kenneth L; Montenieri, John A; Antolin, Michael F

    2009-06-01

    Black-tailed prairie dogs (Cynomys ludovicianus) on the Great Plains of the United States are highly susceptible to plague, caused by the bacterium Yersinia pestis, with mortality on towns during plague epizootics often approaching 100%. The ability of flea-borne transmission to sustain disease spread has been questioned because of inefficiency of flea vectors. However, even with low individual efficiency, overall transmission can be increased if flea abundance (the number of fleas on hosts) increases. Changes in flea abundance on hosts during plague outbreaks were recorded during a large-scale study of plague outbreaks in prairie dogs in north central Colorado during 3 years (2004-2007). Fleas were collected from live-trapped black-tailed prairie dogs before and during plague epizootics and tested by PCR for the presence of Y. pestis. The predominant fleas were two prairie dog specialists (Oropsylla hirsuta and Oropsylla tuberculata cynomuris), and a generalist flea species (Pulex simulans) was also recorded from numerous mammals in the area. The three species differ in seasonal abundance, with greatest abundance in spring (February and March) and fall (September and October). Flea abundance and infestation intensity increased during epizootics and were highest on prairie dogs with Y. pestis-infected fleas. Seasonal occurrence of epizootics among black-tailed prairie dogs was found to coincide with seasonal peaks in flea abundance. Concentration of infected fleas on surviving animals may account for rapid spread of plague during epizootics. In particular, the role of the generalist flea P. simulans was previously underappreciated.

  10. Local persistence and extinction of plague in a metapopulation of great gerbil burrows, Kazakhstan.

    PubMed

    Schmid, B V; Jesse, M; Wilschut, L I; Viljugrein, H; Heesterbeek, J A P

    2012-12-01

    Speculation on how the bacterium Yersinia pestis re-emerges after years of absence in the Prebalkhash region in Kazakhstan has been ongoing for half a century, but the mechanism is still unclear. One of the theories is that plague persists in its reservoir host (the great gerbil) in so-called hotspots, i.e. small regions in which the conditions remain favourable for plague to persist during times where the conditions in the Prebalkhash region as a whole have become unfavourable for plague persistence. In this paper we use a metapopulation model that describes the dynamics of the great gerbil. With this model we study the minimum size of an individual hotspot and the combined size of multiple hotspots in the Prebalkhash region that would be required for Y. pestis to persist through an inter-epizootic period. We show that the combined area of hotspots required for plague persistence is so large that it would be unlikely to have been missed by existing plague surveillance. This suggests that persistence of plague in that region cannot solely be explained by the existence of hotspots, and therefore other hypotheses, such as survival in multiple host species, and persistence in fleas or in the soil should be considered as well.

  11. Flea, rodent, and plague ecology at Chuchupate Campground, Ventura County, California.

    PubMed

    Davis, Richard M; Smith, Randall T; Madon, Minoo B; Sitko-Cleugh, Erika

    2002-06-01

    Chuchupate Campground in Ventura County, California, was closed to the public for 18 years (1982 to 2000) because of uncontrolled vector fleas and persistent plague antibody titers in rodents. The primary purpose of this study was to clarify the plague ecology of Chuchupate Campground by identifying involved rodents and their vector fleas and by determining many of their ecological parameters: abundance, flea and host preferences and diversities, and flea seasonality. Rodents and fleas were identified to species, some fleas were tested for Yersinia pestis, and rodent bloods were analyzed for the presence of antibodies to Y. pestis. During this study, 20 flea species were identified from 10 rodent and one lagomorph species collected. Five species of rodents were seropositive for plague during 13 of the 17 years in which plague testing was conducted. A likely reservoir species was not determined, but evidence of plague resistance was discovered in Merriam's chipmunks (Tamias merriami) and dusky-footed woodrats (Neotoma fuscipes). The "susceptible" rodent and flea complexes at Chuchupate are the California ground squirrel (Spermophilus beecheyi) and its fleas, Oropsylla montana and Hoplopsyllus anomalus, Merriam's chipmunk and its flea, Eumolpianusfornacis, and the dusky-footed woodrat and its flea, Orchopeas sexdentatus. Host preference, diversity, and seasonality of fleas are discussed, as well as the pivotal role of woodrat houses and nests as foci for hosts, fleas, and plague.

  12. [Exploration on the fulminating plague in Bianjing in 1232 and the climatic factors].

    PubMed

    Mou, Zhong-Xing

    2008-01-01

    The plague occurred in Bianjing in 1232 was a serious event in the history of Chinese epidemic. It lasted for over 50 days, with a death toll of over 900,000. It is speculated that this is a mass epidemic of pneumonic plague and the pathogen was carried by the Mongolian Army when attacking Bianjing. At that time, the plague spread in Mongolian Army camp and finally involved the suburbs of Bianjing. After the army withdrawal, when Bianjing residents and soldiers went out of the city to collect foods and were unfortunately infected, and thus this dangerous infectious disease was transmitted into the city from the suburbs. Soon, the plague broke out and became epidemic in Bianjing during the 27-day period of 5 May-1 June, because of the cold snap rushed upon Bianjing on 1 June, the unusual weather was the motive for the mass epidemic of the plague. By then, it was popularly recognized as "exogenous cold damage". At present, facing the global climatologic changes, it is of great practical significance to explore the rich materials of plague and the climatic records accumulated in Chinese medicine.

  13. Comparative Genomics of 2009 Seasonal Plague (Yersinia pestis) in New Mexico

    PubMed Central

    Gibbons, Henry S.; Onischuk, Lisa; Leonard, Pascale; Broomall, Stacey; Sickler, Todd; Betters, Janet L.; McGregor, Paul; Donarum, Greg; Liem, Alvin; Fochler, Ed; McNew, Lauren; Rosenzweig, C. Nicole; Skowronski, Evan

    2012-01-01

    Plague disease caused by the Gram-negative bacterium Yersinia pestis routinely affects animals and occasionally humans, in the western United States. The strains native to the North American continent are thought to be derived from a single introduction in the late 19th century. The degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of North American plague are highly desired. To assay genetic diversity of plague isolates within confined geographic areas, draft genome sequences were generated by 454 pyrosequencing from nine environmental and clinical plague isolates. In silico assemblies of Variable Number Tandem Repeat (VNTR) loci were compared to laboratory-generated profiles for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels) were compared to previously sequenced Y. pestis isolates. The resulting panel of mutations allowed clustering of the strains and tracing of the most likely evolutionary trajectory of the plague strains. The sequences also allowed the identification of new putative SNPs that differentiate the 2009 isolates from previously sequenced plague strains and from each other. In addition, new insertion points for the abundant insertion sequences (IS) of Y. pestis are present that allow additional discrimination of strains; several of these new insertions potentially inactivate genes implicated in virulence. These sequences enable whole-genome phylogenetic analysis and allow the unbiased comparison of closely related isolates of a genetically monomorphic pathogen. PMID:22359605

  14. Small mammal distribution and diversity in a plague endemic area in West Usambara Mountains, Tanzania.

    PubMed

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

    2014-07-01

    Small mammals play a role in plague transmission as hosts in all plague endemic areas. Information on distribution and diversity of small mammals is therefore important for plague surveillance and control in such areas. The objective of this study was to investigate small mammals' diversity and their distribution in plague endemic area in the West Usambara Mountains in north-eastern Tanzania. Landsat images and field surveys were used to select trapping locations in different landscapes. Three landscapes with different habitats were selected for trapping of small mammals. Three types of trap were used in order to maximise the number of species captured. In total, 188 animals and thirteen species were captured in 4,905 trap nights. Praomys delectorum and Mastomys natalensis both reported as plague hosts comprised 50% of all the animals trapped. Trap success increased with altitude. Species diversity was higher in plantation forest followed by shrub, compared to other habitats, regardless of landscape type. It would therefore seem that chances of plague transmission from small mammals to humans are much higher under shrub, natural and plantation forest habitats.

  15. Are plague pits of particular use to palaeoepidemiologists?

    PubMed

    Waldron, H A

    2001-02-01

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

  16. Potential role of viruses in white plague coral disease.

    PubMed

    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. [Recombinant viruses of poultry as vector vaccines against fowl plague].

    PubMed

    Fuchs, Walter; Veits, Jutta; Mettenleiter, Thomas C

    2006-01-01

    To help in the control of fowl plague caused by highly pathogenic avian influenza A viruses of hemagglutinin (HA) subtypes H5 and H7 several vaccines have been developed. A prophylactic immunization of poultry with inactivated influenza viruses in non-endemic situations is questionable, however, due to the impairment of serological identification of field virus-infected animals which hinders elimination of the infectious agent from the population. This problem might be overcome by the use of genetically engineered marker vaccines which contain only the protective influenza virus hemagglutinin. Infected animals could then be unambiguously identified by their serum antibodies against other influenza virus proteins, e.g. neuraminidase or nucleoprotein. For such a use, purified HA or HA-expressing DNA vaccines are conceivable. Economically advantageous and easier to apply are modified live virus vaccines in use against other poultry diseases, which have been modified to express influenza virus HA. So far, recombinant HA-expressing fowlpox virus (FPV) as well as infectious laryngotracheitis and Newcastle disease viruses have been asssessed in animal experiments. An H5-expressing FPV recombinant is already in use in Central America and Southeast Asia but without accompanying marker diagnostics. Advantages and disadvantages of the different viral vectors are discussed.

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

    USGS Publications Warehouse

    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.

  19. Duration of plague (Yersinia pestis) outbreaks in black-tailed prairie dog (Cynomys ludovicianus) colonies of northern Colorado.

    PubMed

    St Romain, Krista; Tripp, Daniel W; Salkeld, Daniel J; Antolin, Michael F

    2013-09-01

    Plague, caused by the bacterium Yersinia pestis, triggers die-offs in colonies of black-tailed prairie dogs (Cynomys ludovicianus), but the time-frame of plague activity is not well understood. We document plague activity in fleas from prairie dogs and their burrows on three prairie dog colonies that suffered die-offs. We demonstrate that Y. pestis transmission occurs over periods from several months to over a year in prairie dog populations before observed die-offs.

  20. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

    USGS Publications Warehouse

    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.

  1. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs.

    PubMed

    Busch, Joseph D; Van Andel, Roger; Stone, Nathan E; Cobble, Kacy R; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William; Shuey, Megan M; Foster, Jeffrey T; Schupp, James M; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L; Rocke, Tonie E; Wagner, David M

    2013-10-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  2. Sylvatic Plague Vaccine Partially Protects Prairie Dogs (Cynomys spp.) in Field Trials.

    PubMed

    Rocke, Tonie E; Tripp, Daniel W; Russell, Robin E; Abbott, Rachel C; Richgels, Katherine L D; 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

    2017-06-22

    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.

  3. Sylvatic plague vaccine partially protects prairie dogs (Cynomys spp.) in field trials

    USGS Publications Warehouse

    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.

  4. Immune responses to plague infection in wild Rattus rattus, in Madagascar: a role in foci persistence?

    PubMed

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

  5. Immune Responses to Plague Infection in Wild Rattus rattus, in Madagascar: A Role in Foci Persistence?

    PubMed Central

    Andrianaivoarimanana, Voahangy; Telfer, Sandra; Rajerison, Minoarisoa; Ranjalahy, Michel A.; Andriamiarimanana, Fehivola; Rahaingosoamamitiana, Corinne; Rahalison, Lila; Jambou, Ronan

    2012-01-01

    Background Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci. Methodology/Principal Findings We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks. Conclusion/Significance Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission. PMID

  6. A historical vignette (15). "Be proud of yourself: you have a history!" The nose and the plague.

    PubMed

    Tainmont, J

    2009-01-01

    The nose and the plague. Although the plague does not cause any specific nasal pathology, the miasma theory and the repulsive smell of the disease were factors that contributed to a strong emphasis on the nose. To stop the spread of the disease, it was thought necessary to saturate the nose with protective scents (hence the nose of the plague doctors) (Figure 1), or simply to hold one's nose. Moreover, the nose was long considered to be an outlet for mucus from the encephalon, and so induced nose bleeding and sneezing were advised when the plague seemed to be attacking the brain.

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

    PubMed Central

    2010-01-01

    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. PMID:20973955

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

    PubMed

    Davis, S; Trapman, P; Leirs, H; Begon, M; Heesterbeek, J A P

    2008-07-31

    Percolation theory is most commonly associated with the slow flow of liquid through a porous medium, with applications to the physical sciences. Epidemiological applications have been anticipated for disease systems where the host is a plant or volume of soil, and hence is fixed in space. However, no natural examples have been reported. The central question of interest in percolation theory, 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) in populations of great gerbils (Rhombomys opimus) in Kazakhstan have been used to show that epizootics only occur when more than about 0.33 of the burrow systems built by the host are occupied by family groups. The underlying mechanism for this abundance threshold is unknown. Here we present evidence that it is a percolation threshold, which arises from the difference in scale between the movements that transport infectious fleas between family groups and the vast size of contiguous landscapes colonized by gerbils. Conventional theory predicts that abundance thresholds for the spread of infectious disease arise when transmission between hosts is density dependent such that the basic reproduction number (R(0)) increases with abundance, attaining 1 at the threshold. Percolation thresholds, however, are separate, spatially explicit thresholds that indicate long-range connectivity in a system and do not coincide with R(0) = 1. 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. This first natural example of a percolation threshold in a disease system invites a re-appraisal of other invasion thresholds, such as those for epidemic viral infections in African lions (Panthera leo), and of other disease systems such as bovine tuberculosis (caused by Mycobacterium bovis) in

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

    PubMed

    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.

  10. Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

    PubMed

    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.

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

    PubMed

    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.

  12. Gene flow in a Yersinia pestis vector, Oropsylla hirsuta, during a plague epizootic.

    PubMed

    Jones, Philip H; Washburn, Leigh R; Britten, Hugh B

    2011-09-01

    Appreciating how Yersinia pestis, the etiological agent of plague, spreads among black - tailed prairie dog (Cynomys ludovicianus) colonies (BTPD), is vital to wildlife conservation programs in North American grasslands. A little - studied aspect of the system is the role of Y. pestis vectors, i.e. fleas, play in the spreading of plague in natural settings. We investigated the genetic structure and variability of a common prairie dog flea (Oropsylla hirsuta) in BTPD colonies in order to examine dispersal patterns. Given that this research took place during a widespread plague epizootic, there was the added advantage of gaining information on the dynamics of sylvatic plague. Oropsylla hirsuta were collected from BTPD burrows in nine colonies from May 2005 to July 2005, and eight polymorphic microsatellite markers were used to generate genotypic data from them. Gene flow estimates revealed low genetic differentiation among fleas sampled from different colonies. NestedPCR plague assays confirmed the presence of Y. pestis with the average Y. pestis prevalence across all nine colonies at 12%. No significant correlations were found between the genetic variability and gene flow of O. hirsuta and Y. pestis prevalence on a per -colony basis. Oropsylla hirsuta dispersal among BTPD colonies was high, potentially explaining the rapid spread of Y. pestis in our study area in 2005 and 2006.

  13. Sylvatic plague reduces genetic variability in black-tailed prairie dogs.

    PubMed

    Trudeau, Kristie M; Britten, Hugh B; Restani, Marco

    2004-04-01

    Small, isolated populations are vulnerable to loss of genetic diversity through in-breeding and genetic drift. Sylvatic plague due to infection by the bacterium Yersinia pestis caused an epizootic in the early 1990s resullting in declines and extirpations of many black-tailed prairie dog (Cynomys ludovicianus) colonies in north-central Montana, USA. Plague-induced population bottlenecks may contribute to significant reductions in genetic variability. In contrast, gene flow maintains genetic variability within colonies. We investigated the impacts of the plague epizootic and distance to nearest colony on levels of genetic variability in six prairie dog colonies sampled between June 1999 and July 2001 using 24 variable randomly amplified polymorphic DNA (RAPD) markers. Number of effective alleles per locus (n(e)) and gene diversity (h) were significantly decreased in the three colonies affected by plague that were recovering from the resulting bottlenecks compared with the three colonies that did not experience plague. Genetic variability was not significantly affected by geographic distance between colonies. The majority of variance in gene fieqnencies was found within prairie clog colonies. Conservation of genetic variability in black-tailed prairie dogs will require the preservation of both large and small colony complexes and the gene flow amonog them.

  14. Vegetation habitats and small mammals in a plague endemic area in Western Usambara Mountains, Tanzania.

    PubMed

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

    2014-07-01

    Human plague still exists in different parts of the world, including some landscapes in north-eastern Tanzania. Wherever the hotspot of plague, small mammals seem to play a key role as host. The objective of this study was to investigate the relationship between vegetation habitats types and small mammals in a plague endemic area of Lushoto District in Tanzania. A combination of field survey and Landsat images was used to identify the vegetation habitats. Small mammals were trapped in the mapped vegetation units, and identified. In total, six main types of vegetation habitats were investigated. A total of 13 small mammal species, potentially related to plague were trapped. Results show that annual cultivated crops habitat accounted for 80% of Mastomys natalensis while natural forest accounted for 60% of Praomys delectorum. These findings have shed new light on the diversity of rodents in different habitats of natural and semi-natural vegetations, and agricultural crops in the study area, which is an important intermediate step in unravelling the complex human plague system.

  15. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007.

    PubMed

    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.

  16. Influence of satellite-derived rainfall patterns on plague occurrence in northeast Tanzania.

    PubMed

    Debien, Annekatrien; Neerinckx, Simon; Kimaro, Didas; Gulinck, Hubert

    2010-12-13

    In the tropics, rainfall data are seldom accurately recorded, and are often discontinuous in time. In the scope of plague-research in northeast Tanzania, we adapted previous research to reconstruct rainfall patterns at a suitable resolution (1 km), based on time series of NDVI: more accurate satellite imagery was used, in the form of MODIS NDVI, and rainfall data were collected from the TRMM sensors instead of in situ data. First, we established a significant relationship between monthly rainfall and monthly composited MODIS NDVI. The established linear relationship was then used to reconstruct historic precipitation patterns over a mountainous area in northeastern Tanzania. We validated the resulting precipitation estimates with in situ rainfall time series of three meteorological stations located in the study area. Taking the region's topography into account, a correlation coefficient of 0.66 was obtained for two of the three meteorological stations. Our results suggest that the adapted strategy can be applied fruitfully to estimate rainfall variability and seasonality, despite the underestimation of overall rainfall rates. Based on this model, rainfall in previous years (1986) is modelled to obtain a dataset with which we can compare plague occurrence in the area. A positive correlation of 82% is obtained between high rainfall rates and plague incidence with a two month lag between rainfall and plague cases. We conclude that the obtained results are satisfactory in support of the human plague research in which this study is embedded, and that this approach can be applied in other studies with similar goals.

  17. [Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010].

    PubMed

    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