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Sample records for lethal plague challenge

  1. Recombinant raccoon pox vaccine protects mice against lethal plague

    Science.gov (United States)

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

    2003-01-01

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

  2. Plague

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    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.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.

    Science.gov (United States)

    Wang, Shixia; Goguen, Jon D; Li, Fusheng; Lu, Shan

    2011-09-09

    Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2011-01-01

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

  6. Plague Symptoms

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    ... 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 ...

  7. Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice.

    Science.gov (United States)

    Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M; Branger, Christine G; Tinge, Steven A; Curtiss, Roy

    2010-06-01

    A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

  8. Fine-Tuning Synthesis of Yersinia pestis LcrV from Runaway-Like Replication Balanced-Lethal Plasmid in a Salmonella enterica Serovar Typhimurium Vaccine Induces Protection against a Lethal Y. pestis Challenge in Mice▿

    Science.gov (United States)

    Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M.; Branger, Christine G.; Tinge, Steven A.; Curtiss, Roy

    2010-01-01

    A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal ΔasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain χ9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/Pcro) (PR), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC PBAD c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of β-lactamase, and cloned into pYA4534 under the control of the Ptrc promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain χ9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route. PMID:20308296

  9. The bureaucratization of war: moral challenges exemplified by the covert lethal drone

    Directory of Open Access Journals (Sweden)

    Richard Adams

    2013-12-01

    Full Text Available This article interrogates the bureaucratization of war, incarnate in the covert lethal drone. Bureaucracies are criticized typically for their complexity, inefficiency, and inflexibility. This article is concerned with their moral indifference. It explores killing, which is so highly administered, so morally remote, and of such scale, that we acknowledge a covert lethal program. This is a bureaucratized program of assassination in contravention of critical human rights. In this article, this program is seen to compromise the advance of global justice. Moreover, the bureaucratization of lethal force is seen to dissolve democratic ideals from within. The bureaucracy isolates the citizens from lethal force applied in their name. People are killed, in the name of the State, but without conspicuous justification, or judicial review, and without informed public debate. This article gives an account of the risk associated with the bureaucratization of the State's lethal power. Exemplified by the covert drone, this is power with formidable reach. It is power as well, which requires great moral sensitivity. Considering the drone program, this article identifies challenges, which will become more prominent and pressing, as technology advances.

  10. Plague: Frequently Asked Questions

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

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

    Science.gov (United States)

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

    2011-01-01

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

  12. Plague Prevention

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

  13. Galantamine is a novel post-exposure therapeutic against lethal VX challenge

    International Nuclear Information System (INIS)

    Hilmas, Corey J.; Poole, Melissa J.; Finneran, Kathryn; Clark, Matthew G.; Williams, Patrick T.

    2009-01-01

    The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 μg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

  14. A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

    Science.gov (United States)

    Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

    2009-08-06

    CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

  15. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

    Science.gov (United States)

    Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  16. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    Science.gov (United States)

    Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

    2016-01-01

    Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

  17. Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

    Directory of Open Access Journals (Sweden)

    Krishnamurthy Konduru

    Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

  18. A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice.

    Directory of Open Access Journals (Sweden)

    Julie L Dutton

    Full Text Available While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2 challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials.

  19. Duck plague

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    Friend, M.

    1999-01-01

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

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

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    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.

  1. Plague Maps and Statistics

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    ... and Statistics Recommend on Facebook Tweet Share Compartir Plague in the United States Plague was first introduced ... them at higher risk. Reported Cases of Human Plague - United States, 1970-2016 Since the mid–20th ...

  2. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  3. Inactivated recombinant plant virus protects dogs from a lethal challenge with canine parvovirus.

    Science.gov (United States)

    Langeveld, J P; Brennan, F R; Martínez-Torrecuadrada, J L; Jones, T D; Boshuizen, R S; Vela, C; Casal, J I; Kamstrup, S; Dalsgaard, K; Meloen, R H; Bendig, M M; Hamilton, W D

    2001-06-14

    A vaccine based upon a recombinant plant virus (CPMV-PARVO1), displaying a peptide derived from the VP2 capsid protein of canine parvovirus (CPV), has previously been described. To date, studies with the vaccine have utilized viable plant chimaeric particles (CVPs). In this study, CPMV-PARVO1 was inactivated by UV treatment to remove the possibility of replication of the recombinant plant virus in a plant host after manufacture of the vaccine. We show that the inactivated CVP is able to protect dogs from a lethal challenge with CPV following parenteral immunization with the vaccine. Dogs immunized with the inactivated CPMV-PARVO1 in adjuvant displayed no clinical signs of disease and shedding of CPV in faeces was limited following CPV challenge. All immunized dogs elicited high titres of peptide-specific antibody, which neutralized CPV in vitro. Levels of protection, virus shedding and VP2-specific antibody were comparable to those seen in dogs immunized with the same VP2- peptide coupled to keyhole limpet hemocyanin (KLH). Since plant virus-derived vaccines have the potential for cost-effective manufacture and are not known to replicate in mammalian cells, they represent a viable alternative to current replicating vaccine vectors for development of both human and veterinary vaccines.

  4. New baculovirus recombinants expressing Pseudorabies virus (PRV) glycoproteins protect mice against lethal challenge infection.

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    Grabowska, Agnieszka K; Lipińska, Andrea D; Rohde, Jörg; Szewczyk, Boguslaw; Bienkowska-Szewczyk, Krystyna; Rziha, Hanns-Joachim

    2009-06-02

    The present study demonstrates the protective potential of novel baculovirus recombinants, which express the glycoproteins gB, gC, or gD of Pseudorabies virus (PRV; Alphaherpesvirus of swine) and additionally contain the glycoprotein G of Vesicular Stomatitis Virus (VSV-G) in the virion (Bac-G-PRV). To evaluate the protective capacity, mixtures of equal amounts of the PRV gB-, gC-, and gD-expressing baculoviruses were used for immunization. Three intramuscular immunizations with that Bac-G-PRV mixture could protect mice against a lethal PRV challenge infection. To achieve complete protection high titers of Bac-G-PRV and three immunizations were necessary. This immunization with Bac-G-PRV resulted in the induction of high titers of PRV-specific serum antibodies of the IgG2a subclass and of interferon (IFN)-gamma, indicating a Th1-type immune response. Moreover, splenocytes of immunized mice exhibited natural killer cell activity accompanied by the production of IFN-alpha and IFN-gamma. Collectively, the presented data demonstrate for the first time that co-expression of VSV-G in baculovirus recombinant vaccines can improve the induction of a protective immune response against foreign antigens.

  5. Characterization of leptospiral proteins that afford partial protection in hamsters against lethal challenge with Leptospira interrogans.

    Science.gov (United States)

    Atzingen, Marina V; Gonçales, Amane P; de Morais, Zenaide M; Araújo, Eduardo R; De Brito, Thales; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2010-09-01

    Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. The whole-genome sequence of Leptospira interrogans serovar Copenhageni together with bioinformatic tools allow us to search for novel antigen candidates suitable for improved vaccines against leptospirosis. This study focused on three genes encoding conserved hypothetical proteins predicted to be exported to the outer membrane. The genes were amplified by PCR from six predominant pathogenic serovars in Brazil. The genes were cloned and expressed in Escherichia coli strain BL21-SI using the expression vector pDEST17. The recombinant proteins tagged with N-terminal 6xHis were purified by metal-charged chromatography. The proteins were recognized by antibodies present in sera from hamsters that were experimentally infected. Immunization of hamsters followed by challenge with a lethal dose of a virulent strain of Leptospira showed that the recombinant protein rLIC12730 afforded statistically significant protection to animals (44 %), followed by rLIC10494 (40 %) and rLIC12922 (30 %). Immunization with these proteins produced an increase in antibody titres during subsequent boosters, suggesting the involvement of a T-helper 2 response. Although more studies are needed, these data suggest that rLIC12730 and rLIC10494 are promising candidates for a multivalent vaccine for the prevention of leptospirosis.

  6. USC-087 protects Syrian hamsters against lethal challenge with human species C adenoviruses.

    Science.gov (United States)

    Toth, Karoly; Spencer, Jacqueline F; Ying, Baoling; Tollefson, Ann E; Hartline, Caroll B; Richard, Eric T; Fan, Jiajun; Lyu, Jinglei; Kashemirov, Boris A; Harteg, Cheryl; Reyna, Dawn; Lipka, Elke; Prichard, Mark N; McKenna, Charles E; Wold, William S M

    2018-05-01

    Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, AdV can cause serious infection in severely immunosuppressed individuals, especially pediatric patients undergoing allogeneic hematopoietic stem cell transplantation, where mortality rates are up to 80% with disseminated disease. Despite the seriousness of AdV disease, there are no drugs approved specifically to treat AdV infections. We report here that USC-087, an N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analog of cidofovir, is highly effective against multiple AdV types in cell culture. USC-087 is also effective against AdV-C6 in our immunosuppressed permissive Syrian hamster model. In this model, hamsters are immunosuppressed by treatment with high dose cyclophosphamide. Injection of AdV-C6 (or AdV-C5) intravenously leads to a disseminated infection that resembles the disease seen in humans, including death. We have tested the efficacy of orally-administered USC-087 against the median lethal dose of intravenously administered AdV-C6. USC-087 completely prevented or significantly decreased mortality when administered up to 4 days post challenge. USC-087 also prevented or significantly decreased liver damage caused by AdV-C6 infection, and suppressed virus replication even when administered 4 days post challenge. These results imply that USC-087 is a promising candidate for drug development against HAdV infections. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.

    Directory of Open Access Journals (Sweden)

    Misako Yoneda

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G. Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi. Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

  8. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Stone, Nathan E.; Cobble, Kacy R.; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William E.; Shuey, Megan M.; Foster, Jeffrey T.; Schupp, James M.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L.; Rocke, Tonie E.; Wagner, David M.

    2013-01-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  9. Plague Diagnosis and Treatment

    Science.gov (United States)

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

  10. Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge.

    Science.gov (United States)

    Dahl, Lotte; Jensen, Trine Hammer; Gottschalck, Elisabeth; Karlskov-Mortensen, Peter; Jensen, Tove Dannemann; Nielsen, Line; Andersen, Mads Klindt; Buckland, Robin; Wild, T Fabian; Blixenkrone-Møller, Merete

    2004-09-09

    We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (CDV) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect CDV infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease.

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

    Directory of Open Access Journals (Sweden)

    Anne Derbise

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

  12. A novel challenge test incorporating irradiation (60Co) of compost sub-samples to validate thermal lethality towards pathogenic bacteria.

    Science.gov (United States)

    Moore, John E; Watabe, Miyuki; Stewart, Andrew; Cherie Millar, B; Rao, Juluri R

    2009-01-01

    Maturing compost heaps normally attaining temperatures ranging from 55 to 65 degrees C is generally regarded to conform to recommended biological risks and sanitation standards for composts stipulated by either EU or US-EPA. Composted products derived from animal sources are further required by EU biohazard safety regulatory legislation that such composts either attain 70 degrees C for over 3h during maturation or via treatment at 70 degrees C for 1h before being considered for dispensation on land. The setting of the upper limit of thermal lethality at 70 degrees C/1h for achieving biosecurity of the animal waste composted products (e.g. pelleted fertilizer formulations) is not properly substantiated by specific validation tests, comprising a 'wipe-out' step (usually via autoclaving) followed by inoculation of a prescribed bacterium, exposure to 70 degrees C/1h and the lethality determined. Pelleted formulations of composts are not amenable for wet methods (autoclaving) for wipe-out sterilization step as this is detrimental to the pellet and compromises sample integrity. This study describes a laboratory method involving the employment of ((60)Co) irradiation 'wipe-out' step to: (a) compost sub-samples drawn from compost formulation heaps and (b) pelleted products derived from composted animal products while determining the thermal lethality of a given time/temperature (70 degrees C/1h) treatment process and by challenging the irradiated sample (not just with one bacterium but), out with 10 potential food-poisoning organisms from the bacterial genera (Campylobacter, Escherichia, Listeria, Salmonella, Yersinia) frequently detected in pig and poultry farm wastes. This challenge test on compost sub-samples can be a useful intervention ploy for 'inspection and validation' technique for composters during the compost maturity process, whose attainment of temperatures of 55-65 degrees C is presumed sufficient for attainment of sanitation. Stringent measures are further

  13. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Directory of Open Access Journals (Sweden)

    Noam Cohen

    Full Text Available Mice are exceedingly sensitive to intra-peritoneal (IP challenge with some virulent pneumococci (LD50 = 1 bacterium. To investigate how peripheral contact with bacterial capsular polysaccharide (PS antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1 The PS co-localized with MHC molecules on the BMDC surface; 2 PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3 Type-specific resistance to lethal IP challenge was manifested only after day 5; 4 Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5 Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6 Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  14. Enzootic plague foci, Algeria

    Directory of Open Access Journals (Sweden)

    M.A. Malek

    2015-03-01

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

  15. Protect Yourself from Plague

    Science.gov (United States)

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

  16. Recombinant rabies virus expressing the H protein of canine distemper virus protects dogs from the lethal distemper challenge.

    Science.gov (United States)

    Wang, Feng-Xue; Zhang, Shu-Qin; Zhu, Hong-Wei; Yang, Yong; Sun, Na; Tan, Bin; Li, Zhen-Guang; Cheng, Shi-Peng; Fu, Zhen F; Wen, Yong-Jun

    2014-12-05

    The rabies virus (RV) vector LBNSE expressing foreign antigens have shown considerable promise as vaccines against viral and bacteria diseases, which is effective and safe. We produced a new RV-based vaccine vehicle expressing 1.824 kb hemagglutinin (H) gene of the canine distemper virus (CDV) by reverse genetics technology. The recombinant virus LBNSE-CDV-H retained growth properties similar to those of vector LBNSE both in BSR and mNA cell culture. The H gene of CDV was expressed and detected by immunostaining. To compare the immunogenicity of LBNSE-CDV-H, dogs were immunized with each of these recombinant viruses by intramuscular (i.m.). The dogs were bled at third weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with virulent virus (ZJ 7) at fourth weeks. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. Dogs inoculated with LBNSE-CDV-H showed no any signs of disease and exhibited seroconversion against both RV and CDV H protein. The LBNSE-CDV-H did not cause disease in dogs and conferred protection from challenge with a lethal wild type CDV strain, demonstrating its potential value for wildlife conservation efforts. Together, these studies suggest that recombinant RV expressing H protein from CDV stimulated high levels of adaptive immune responses (VNA), and protected all dogs challenge infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. A Bioprocessed Polysaccharide from Lentinus edodes Mycelia Cultures with Turmeric Protects Chicks from a Lethal Challenge of Salmonella Gallinarum.

    Science.gov (United States)

    Han, Dalmuri; Lee, Hyung Tae; Lee, June Bong; Kim, Yongbaek; Lee, Sang Jong; Yoon, Jang Won

    2017-02-01

    Our previous studies demonstrated that a bioprocessed polysaccharide (BPP) isolated from Lentinus edodes mushroom mycelia cultures supplemented with black rice bran can protect mice against Salmonella lipopolysaccharide-induced endotoxemia and reduce the mortality from Salmonella Typhimurium infection through upregulated T-helper 1 immunity. Here, we report that a BPP from L. edodes mushroom mycelia liquid cultures supplemented with turmeric (referred to as BPP-turmeric) alters chicken macrophage responses against avian-adapted Salmonella Gallinarum and protects chicks against a lethal challenge from Salmonella Gallinarum. In vitro analyses revealed that the water extract of BPP-turmeric (i) changed the protein expression or secretion profile of Salmonella Gallinarum, although it was not bactericidal, (ii) reduced the phagocytic activity of the chicken-derived macrophage cell line HD-11 when infected with Salmonella Gallinarum, and (iii) significantly activated the transcription expression of interleukin (IL)-1β, IL-10, tumor necrosis factor α, and inducible nitric oxide synthase in response to various Salmonella infections, whereas it repressed that of IL-4, IL-6, interferon-β, and interferon-γ. We also found that BPP-turmeric (0.1 g/kg of feed) as a feed additive provided significant protection to 1-day-old chicks infected with a lethal dose of Salmonella Gallinarum. Collectively, these results imply that BPP-turmeric contains biologically active component(s) that protect chicks against Salmonella Gallinarum infection, possibly by regulating macrophage immune responses. Further studies are needed to evaluate the potential efficacy of BPP-turmeric as a livestock feed additive for the preharvest control of fowl typhoid or foodborne salmonellosis.

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

    Science.gov (United States)

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

    2016-11-11

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

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

    Science.gov (United States)

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

    2014-07-10

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

  20. Liposome-antigen-nucleic acid complexes protect mice from lethal challenge with western and eastern equine encephalitis viruses.

    Science.gov (United States)

    Phillips, Aaron T; Schountz, Tony; Toth, Ann M; Rico, Amber B; Jarvis, Donald L; Powers, Ann M; Olson, Ken E

    2014-02-01

    Alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. Western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense. However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigen-nucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.

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

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

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

  2. An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

    Science.gov (United States)

    Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

    2013-07-09

    Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

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

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

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

  4. [The Antonine plague].

    Science.gov (United States)

    Haas, Charles

    2006-01-01

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

  5. BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1(-/- Mice from Monkeypoxvirus Lethal Challenge.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    2015-06-01

    Full Text Available Monkeypox virus (MPXV is the etiological agent of human (MPX. It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV, and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4 vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4-A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events following intraperitoneal administration. Further, BoHV-4-A-EF1α-M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1(-/- mice

  6. Human plague occurrences in Africa

    DEFF Research Database (Denmark)

    Neerinckx, Simon; Bertherat, Eric; Leirs, Herwig

    2010-01-01

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

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

    Science.gov (United States)

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

    2011-11-01

    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.

  8. Plague in Yosemite

    Centers for Disease Control (CDC) Podcasts

    2017-03-23

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

  9. Plague in Uganda

    Centers for Disease Control (CDC) Podcasts

    2018-01-25

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

  10. Lovastatin protects against experimental plague in mice.

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    Saravanan Ayyadurai

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

  11. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

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    John M. Dye

    2016-04-01

    Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

  12. Molecular history of plague.

    Science.gov (United States)

    Drancourt, M; Raoult, D

    2016-11-01

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

  13. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study.

    Science.gov (United States)

    Geisbert, Thomas W; Lee, Amy C H; Robbins, Marjorie; Geisbert, Joan B; Honko, Anna N; Sood, Vandana; Johnson, Joshua C; de Jong, Susan; Tavakoli, Iran; Judge, Adam; Hensley, Lisa E; Maclachlan, Ian

    2010-05-29

    We previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever. A combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections. Defense Threat Reduction Agency. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Plague: Clinics, Diagnosis and Treatment.

    Science.gov (United States)

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

    2016-01-01

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

  15. Plague and Climate: Scales Matter

    Science.gov (United States)

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

    2011-01-01

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

  16. A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.

    Science.gov (United States)

    Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G

    2016-04-29

    Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P ≤ 0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. [Plague in Zaire].

    Science.gov (United States)

    Janssens, P G; Pattyn, S R

    1994-01-01

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

  18. The type IV pilin of Burkholderia mallei is highly immunogenic but fails to protect against lethal aerosol challenge in a murine model.

    Science.gov (United States)

    Fernandes, Paula J; Guo, Qin; Waag, David M; Donnenberg, Michael S

    2007-06-01

    Burkholderia mallei is the cause of glanders and a proven biological weapon. We identified and purified the type IV pilin protein of this organism to study its potential as a subunit vaccine. We found that purified pilin was highly immunogenic. Furthermore, mice infected via sublethal aerosol challenge developed significant increases in titers of antibody against the pilin, suggesting that it is expressed in vivo. Nevertheless, we found no evidence that high-titer antipilin antisera provided passive protection against a sublethal or lethal aerosol challenge and no evidence of protection afforded by active immunization with purified pilin. These results contrast with the utility of type IV pilin subunit vaccines against other infectious diseases and highlight the need for further efforts to identify protective responses against this pathogen.

  19. Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge.

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    Subaschandrabose Rajesh Kumar

    Full Text Available Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9 was protected against both H7N9 (A/Sh2/2013 and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211 in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA

  20. Lethal Epistaxis.

    Science.gov (United States)

    Byard, Roger W

    2016-09-01

    Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

  1. A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

    Directory of Open Access Journals (Sweden)

    Ye Yu

    2011-06-01

    Full Text Available Abstract Background Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. Results The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. Conclusion BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.

  2. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Directory of Open Access Journals (Sweden)

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  3. Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

    Science.gov (United States)

    Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

    2013-01-01

    A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Plague Vaccines: Status and Future.

    Science.gov (United States)

    Sun, Wei

    2016-01-01

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

  6. Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.

    Science.gov (United States)

    Gowen, Brian B; Bailey, Kevin W; Scharton, Dionna; Vest, Zachery; Westover, Jonna B; Skirpstunas, Ramona; Ikegami, Tetsuro

    2013-05-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Plague and the Human Flea, Tanzania

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  8. Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice

    Directory of Open Access Journals (Sweden)

    Jennifer L. Dankmeyer

    2014-01-01

    Full Text Available The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.

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

    Science.gov (United States)

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

    2016-05-05

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

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

    Science.gov (United States)

    Lewnard, Joseph A; Townsend, Jeffrey P

    2016-12-20

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

  11. An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

    Directory of Open Access Journals (Sweden)

    Chan Chris CS

    2010-01-01

    Full Text Available Abstract Background A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. Results Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. Conclusions These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.

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

    Directory of Open Access Journals (Sweden)

    Xiaodong Xiao

    2010-10-01

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

  13. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

    Science.gov (United States)

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C

    2011-08-05

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-09-01

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

  15. Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge

    International Nuclear Information System (INIS)

    Park, Ki Seok; Lee, Jiyeung; Ahn, So Shin; Byun, Young-Ho; Seong, Baik Lin; Baek, Yun Hee; Song, Min-Suk; Choi, Young Ki; Na, Yun Jeong; Hwang, Inhwan; Sung, Young Chul; Lee, Chang Geun

    2009-01-01

    Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8 + T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.

  16. [Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010].

    Science.gov (United States)

    Donaires, Luis F; Céspedes, Manuel; Valencia, Pedro; Salas, Juan Carlos; Luna, María E; Castañeda, Alex; Peralta, Víctor; Cabezas, César; Pachas, Paul E

    2010-09-01

    Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4). Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

  17. Red Plague Control Plan (RPCP)

    Science.gov (United States)

    Cooke, Robert W.

    2010-01-01

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

  18. The Formula of Plague Narratives

    DEFF Research Database (Denmark)

    Christensen, Jørgen Riber

    2015-01-01

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

  19. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus.

    Science.gov (United States)

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5N x viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5N x viruses and can be used by mass application to protect the poultry industry.

  20. Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge.

    Science.gov (United States)

    Erasmus, Jesse H; Seymour, Robert L; Kaelber, Jason T; Kim, Dal Y; Leal, Grace; Sherman, Michael B; Frolov, Ilya; Chiu, Wah; Weaver, Scott C; Nasar, Farooq

    2018-02-15

    Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines. IMPORTANCE Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored the use of the mosquito-specific alphavirus EILV as an alphavirus vaccine

  1. Early host cell targets of Yersinia pestis during primary pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Roger D Pechous

    Full Text Available Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

  2. Age at Vaccination May Influence Response to Sylvatic Plague Vaccine (SPV) in Gunnison's Prairie Dogs (Cynomys gunnisoni).

    Science.gov (United States)

    Rocke, Tonie E; Tripp, Dan; Lorenzsonn, Faye; Falendysz, Elizabeth; Smith, Susan; Williamson, Judy; Abbott, Rachel

    2015-06-01

    Gunnison's prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or "montane" population and a C. g. zuniensis or "prairie" population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P plague challenge at a much higher rate than adults (P plague in the C. g. gunnisoni or "montane" populations of Gunnison's prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

  3. Age at vaccination may influence response to sylvatic plague vaccine (SPV) in Gunnison’s prairie dogs (Cynomys gunnisoni)

    Science.gov (United States)

    Rocke, Tonie E.; Tripp, Daniel W.; Lorenzsonn, Faye; Falendysz, Elizabeth A.; Smith, Susan; Williamson, Judy L.; Abbott, Rachel C.

    2015-01-01

    Gunnison’s prairie dogs (Cynomys gunnisoni) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or “montane” population and a C. g. zuniensis or “prairie” population for vaccine efficacy and challenge studies. No differences (P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates (P age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults (P ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from plague in the C. g. gunnisoni or “montane” populations of Gunnison’s prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

  4. Plague

    Science.gov (United States)

    The health care provider will perform a physical examination and ask about your symptoms. Tests that may be done include: Blood culture Culture of lymph node aspirate (fluid taken from an affected lymph node or bubo) Sputum culture

  5. Plague

    Science.gov (United States)

    ... agents that pose the highest risk to national security and public health because they can be easily ... Career Stage Postdocs' Guide to Gaining Independence Small Business Programs Compare NIAID’s Small Business Programs High-Priority ...

  6. Plague dynamics are driven by climate variation

    DEFF Research Database (Denmark)

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

    2006-01-01

    The bacterium Yersinia pestis causes bubonic plague. In Central Asia, where human plague is still reported regularly, the bacterium is common in natural populations of great gerbils. By using field data from 1949-1995 and previously undescribed statistical techniques, we show that Y. pestis...

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2018-04-05

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anne Derbise

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

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

    Science.gov (United States)

    Stock, Ingo

    2014-12-01

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

  12. An Adjuvanted A(H5N1) Subvirion Vaccine Elicits Virus-Specific Antibody Response and Improves Protection Against Lethal Influenza Viral Challenge in Mouse Model of Protein Energy Malnutrition.

    Science.gov (United States)

    Jones, Enitra N; Amoah, Samuel; Cao, Weiping; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2017-09-15

    Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination. We demonstrated that mice maintained on a VLP diet succumb to lethal challenge at greater rates than mice maintained on an AP diet, despite comparable immunization regimens. Importantly, there was no virus-induced mortality in both VLP and AP groups of mice when either group was immunized with adjuvanted low-dose A(H5N1) subvirion vaccine. Our results suggest that adjuvanted vaccination in populations where PEM is endemic may be one strategy to boost vaccination-promoted immunity and improve outcomes associated with highly pathogenic A(H5N1). Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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

    African Journals Online (AJOL)

    Small mammals play a role in plague transmission as hosts in all plague endemic areas. Information on distribution and diversity of small mammals is therefore important for plague surveillance and control in such areas. The objective of this study was to investigate small mammals' diversity and their distribution in plague ...

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

    Science.gov (United States)

    Wimsatt, Jeffrey; Biggins, Dean E.

    2009-01-01

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

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

    Science.gov (United States)

    Rocke, Tonie E.; Abbott, Rachel C.

    2012-01-01

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

  16. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Directory of Open Access Journals (Sweden)

    Ashley L Fink

    2017-07-01

    Full Text Available Dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4. At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE by binding to viral antigens and then Fcγ receptors (FcγR on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

  17. Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement.

    Science.gov (United States)

    Fink, Ashley L; Williams, Katherine L; Harris, Eva; Alvine, Travis D; Henderson, Thomas; Schiltz, James; Nilles, Matthew L; Bradley, David S

    2017-07-01

    Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

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

    Science.gov (United States)

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

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. Plague metapopulation dynamics in a natural reservoir

    DEFF Research Database (Denmark)

    Davis, S; Klassovskiy, N; Ageyev, V

    2007-01-01

    The ecology of plague (Yersinia pestis infection) in its ancient foci in Central Asia remains poorly understood. We present field data from two sites in Kazakhstan where the great gerbil (Rhombomys opimus) is the major natural host. Family groups inhabit and defend burrow systems spaced throughout...... the landscape, such that the host population may be considered a metapopulation, with each occupied burrow system a subpopulation. We examine plague transmission within and between family groups and its effect on survival. Transmission of plague occurred disproportionately within family groups although not all...... gerbils became infected once plague entered a burrow system. There were no spatial patterns to suggest that family groups in close proximity to infected burrow systems were more at risk of infection than those far away. At one site, infection increased the chances of burrow-system extinction. Overall...

  20. Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts.

    Science.gov (United States)

    Arlen, Philip A; Singleton, Michael; Adamovicz, Jeffrey J; Ding, Yi; Davoodi-Semiromi, Abdolreza; Daniell, Henry

    2008-08-01

    The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. F1-V mice) or unadjuvanted oral doses (oral F1-V mice). Oral F1-V mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were 2 and 3 orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of 1.02 x 10(6) CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 x 10(4) CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7- to 10-log reduction in the mean bacterial burden in survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower-cost vaccines closer to reality.

  1. Human Plague Risk: Spatial-Temporal Models

    Science.gov (United States)

    Pinzon, Jorge E.

    2010-01-01

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

  2. OBESITY : A MODERN DAY PLAGUE.

    Science.gov (United States)

    Yadav, Yatendra Kumar

    2002-01-01

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

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

    Science.gov (United States)

    Welford, Mark R; Bossak, Brian H

    2009-12-22

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

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

    Directory of Open Access Journals (Sweden)

    Mark R Welford

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

  5. Burrowing Owls, Pulex irritans, and Plague.

    Science.gov (United States)

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

    2015-09-01

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

  6. A novel gE-deleted pseudorabies virus (PRV) provides rapid and complete protection from lethal challenge with the PRV variant emerging in Bartha-K61-vaccinated swine population in China.

    Science.gov (United States)

    Wang, Chun-Hua; Yuan, Jin; Qin, Hua-Yang; Luo, Yuzi; Cong, Xin; Li, Yongfeng; Chen, Jianing; Li, Su; Sun, Yuan; Qiu, Hua-Ji

    2014-06-05

    The currently used Bartha-K61 strain is a very safe and effective vaccine against pseudorabies (PR) and has played a critical role in the control and eradication of PR worldwide. Since late 2011, however, PR reemerged among Bartha-K61-vaccinated pig population in many regions in China. Our previous studies demonstrated that the Bartha-K61 vaccine was unable to provide complete protection from the challenge with the PRV TJ strain (PRVTJ), a representative emerging PRV variant that was isolated from a Bartha-K61-immunized pig farm in Tianjin, China. Here, we generated a gE-deleted PRV, named as rPRVTJ-delgE, based on PRVTJ and evaluated its safety and immunogenicity in pigs. Our results showed that groups of piglets (n=5) immunized with 10(3), 10(4) or 10(5)TCID50 rPRVTJ-delgE did not exhibit clinical signs following immunization and challenge and were protected clinically and virologically from the lethal challenge with PRVTJ as early as 1 week post-immunization, in contrast with the incomplete protection provided by the Bartha-K61 vaccine. These indicate that rPRVTJ-delgE is a promising candidate vaccine for updating Bartha-K61 for the control of the currently epidemic PR in China. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    T.F. Khaydarov

    2014-12-01

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

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

    Science.gov (United States)

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

    2016-02-19

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

  10. Diverse Genotypes of Yersinia pestis Caused Plague in Madagascar in 2007.

    Science.gov (United States)

    Riehm, Julia M; Projahn, Michaela; Vogler, Amy J; Rajerison, Minoaerisoa; Andersen, Genevieve; Hall, Carina M; Zimmermann, Thomas; Soanandrasana, Rahelinirina; Andrianaivoarimanana, Voahangy; Straubinger, Reinhard K; Nottingham, Roxanne; Keim, Paul; Wagner, David M; Scholz, Holger C

    2015-06-01

    Yersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging. DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007. The extracted DNAs were then genotyped using three molecular genotyping methods, including, single nucleotide polymorphism (SNP) typing, multi-locus variable-number tandem repeat analysis (MLVA), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) analysis. These methods provided increasing resolution, respectively. The results of these analyses revealed that, in 2007, ten molecular groups, two newly described here and eight previously identified, were responsible for causing human plague in geographically distinct areas of Madagascar. Plague in Madagascar is caused by numerous distinct types of Y. pestis. Genotyping method choice should be based upon the discriminatory power needed, expense, and available data for any desired comparisons. We conclude that genotyping should be a standard tool used in epidemiological investigations of plague outbreaks.

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

    Science.gov (United States)

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

    2009-01-01

    In previous studies, we demonstrated protection against plague in mice and prairie dogs using a raccoon pox (RCN) virus-vectored vaccine that expressed the F1 capsular antigen of Yersinia pestis. In order to improve vaccine efficacy, we have now constructed additional RCN-plague vaccines containing two different forms of the lcrV (V) gene, including full-length (Vfull) and a truncated form (V307). Mouse challenge studies with Y. pestis strain CO92 showed that vaccination with a combination of RCN-F1 and the truncated V construct (RCN-V307) provided the greatest improvement (P = 0.01) in protection against plague over vaccination with RCN-F1 alone. This effect was mediated primarily by anti-F1 and anti-V antibodies and both contributed independently to increased survival of vaccinated mice.

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

    Science.gov (United States)

    Tuffuor, Akosua N; Payne, Richard

    2017-09-01

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

  13. Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C; Branum, K C

    2000-01-01

    The recall of CD8(+) T-cell memory established by infecting H-2(b) mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8(+) effector and memory T cells specific for the shared, immunodominant D(b)NP(366) epitope were...... greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8(+) memory T-cell pool (10%) by sequential priming with two different influenza A viruses (H3N2-->H1N1......) gave much better protection. Though the H7N7 virus initially grew to equivalent titers in the lungs of naive and double-primed mice, the replicative phase was substantially controlled within 3 days. This tertiary H7N7 challenge caused little increase in the magnitude of the CD8(+) D(b)NP(366)(+) T...

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2009-01-01

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

  16. [The plague in Finland in 1710].

    Science.gov (United States)

    Engström, N G

    1994-01-01

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

  17. Plague and the gallium scan: case report

    International Nuclear Information System (INIS)

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

    1975-01-01

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

  18. Oral vaccination against plague using Yersinia pseudotuberculosis.

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  1. Vaccination of mice using the West Nile virus E-protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects mice against a lethal challenge.

    Directory of Open Access Journals (Sweden)

    Marina De Filette

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime--boost regime with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical. In parallel a heterologous boost with purified recombinant WNV envelope (E protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8(+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.

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

    Directory of Open Access Journals (Sweden)

    Rebecca J Eisen

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Guang Tian

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-10-11

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

  7. Empirical assessment of a threshold model for sylvatic plague

    DEFF Research Database (Denmark)

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

    2007-01-01

    Plague surveillance programmes established in Kazakhstan, Central Asia, during the previous century, have generated large plague archives that have been used to parameterize an abundance threshold model for sylvatic plague in great gerbil (Rhombomys opimus) populations. Here, we assess the model...... examine six hypotheses that could explain the resulting false positive predictions, namely (i) including end-of-outbreak data erroneously lowers the estimated threshold, (ii) too few gerbils were tested, (iii) plague becomes locally extinct, (iv) the abundance of fleas was too low, (v) the climate...

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

    Science.gov (United States)

    Dubyanskiy, Vladimir M; Yeszhanov, Aidyn B

    2016-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-02-07

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

  12. A recombinant novirhabdovirus presenting at the surface the E Glycoprotein from West Nile Virus (WNV is immunogenic and provides partial protection against lethal WNV challenge in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Angella Nzonza

    Full Text Available West Nile Virus (WNV is a zoonotic mosquito-transmitted flavivirus that can infect and cause disease in mammals including humans. Our study aimed at developing a WNV vectored vaccine based on a fish Novirhabdovirus, the Viral Hemorrhagic Septicemia virus (VHSV. VHSV replicates at temperatures lower than 20°C and is naturally inactivated at higher temperatures. A reverse genetics system has recently been developed in our laboratory for VHSV allowing the addition of genes in the viral genome and the recovery of the respective recombinant viruses (rVHSV. In this study, we have generated rVHSV vectors bearing the complete WNV envelope gene (EWNV (rVHSV-EWNV or fragments encoding E subdomains (either domain III alone or domain III fused to domain II (rVHSV-DIIIWNV and rVHSV-DII-DIIIWNV, respectively in the VHSV genome between the N and P cistrons. With the objective to enhance the targeting of the EWNV protein or EWNV-derived domains to the surface of VHSV virions, Novirhadovirus G-derived signal peptide and transmembrane domain (SPG and TMG were fused to EWNV at its amino and carboxy termini, respectively. By Western-blot analysis, electron microscopy observations or inoculation experiments in mice, we demonstrated that both the EWNV and the DIIIWNV could be expressed at the viral surface of rVHSV upon addition of SPG. Every constructs expressing EWNV fused to SPG protected 40 to 50% of BALB/cJ mice against WNV lethal challenge and specifically rVHSV-SPGEWNV induced a neutralizing antibody response that correlated with protection. Surprisingly, rVHSV expressing EWNV-derived domain III or II and III were unable to protect mice against WNV challenge, although these domains were highly incorporated in the virion and expressed at the viral surface. In this study we demonstrated that a heterologous glycoprotein and non membrane-anchored protein, can be efficiently expressed at the surface of rVHSV making this approach attractive to develop new vaccines

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

    DEFF Research Database (Denmark)

    Koch, Christian

    1999-01-01

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

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

    NARCIS (Netherlands)

    Curtis, D.R.

    2016-01-01

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

  15. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  16. The dancing plague: a public health conundrum.

    Science.gov (United States)

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

    1997-07-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  18. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  19. Plague epizootic cycles in Central Asia.

    Science.gov (United States)

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

    2014-06-01

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

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

    African Journals Online (AJOL)

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto ...

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

    Peckham, Robert

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria Cristina Schneider

    2014-02-01

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

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

    Science.gov (United States)

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

    2014-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Óscar Botasso

    2008-10-01

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

  7. Plague in Iran: its history and current status

    Directory of Open Access Journals (Sweden)

    Abdolrazagh Hashemi Shahraki

    2016-07-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    A. J. dos Santos Grácio

    2017-01-01

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

  11. Interspecific comparisons of sylvatic plague in prairie dogs

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

    Eads, David; Biggins, Dean E.

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  14. Dangers of noncritical use of historical plague databases

    NARCIS (Netherlands)

    Roosen, J.; Curtis, D.R.

    2018-01-01

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

  15. Understanding the Persistence of Plague Foci in Madagascar

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maliya Alia Malek

    2016-06-01

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

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

    Science.gov (United States)

    Sghirlanzoni, A; Carella, F

    2000-08-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  19. Sylvatic plague vaccine and management of prairie dogs

    Science.gov (United States)

    Rocke, Tonie E.

    2012-01-01

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

  20. Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

    Science.gov (United States)

    Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

    2016-01-01

    RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

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

    Science.gov (United States)

    2013-01-01

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

  2. Non-Lethal Weapons Program

    Science.gov (United States)

    Sheets Frequently Asked Questions Non-Lethal Weapons FAQs Active Denial System FAQs Human Electro -Muscular Incapacitation FAQs Related Links Business Opportunities Contact JNLWD Congressional Engagement , Wednesday, Sept 20, 2017. The Active Denial System, blunt-impact munitions, dazzling lasers, LRAD 100X

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

    Verzhutsky, D B; Balakhonov, S V

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Caio Graco Zeppelini

    2016-10-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Cuadrada, Coral

    2015-01-01

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

  9. Lethal mechanisms in gastric volvulus.

    Science.gov (United States)

    Omond, Kimberley J; Byard, Roger W

    2017-01-01

    A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

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

    Directory of Open Access Journals (Sweden)

    McMichael Anthony J

    2010-08-01

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

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

    OpenAIRE

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

    2014-01-01

    Background Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. Aims The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence...

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    V. A. Graham

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2001-10-04

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

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

    African Journals Online (AJOL)

    Literature suggests that higher resolution remote sensing data integrated in Geographic Information System (GIS) can provide greater possibility to refine the analysis of land cover and terrain characteristics for explanation of abundance and distribution of plague hosts and vectors and hence of health risk hazards to ...

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

    African Journals Online (AJOL)

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

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

    DEFF Research Database (Denmark)

    Reijniers, Jonas; Davis, Stephen; Begon, Mike

    2012-01-01

    , it is common to assume a threshold defined by the ratio of vector and host abundances. Here, we show in contrast, both from field data and model simulations, that for plague (Yersinia pestis) in Kazakhstan, the invasion threshold quantity is based on the product of its host (Rhombomys opimus) and vector...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Petra C.F. Oyston

    2011-06-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2017-12-11

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

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

    Science.gov (United States)

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

    2015-12-01

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

  6. 45 CORRUPTION, THE STATE AND THE CHALLENGE OF SOCIAL ...

    African Journals Online (AJOL)

    User

    development theory which focuses mainly on socio-economic factors. Another approach ... corruption and the social instability that plagues the country. A healthier ... Corruption, the State and the Challenge of Social Stability in Nigeria - Rev.

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

    OpenAIRE

    Bos, Kirsten I; Herbig, Alexander; Sahl, Jason; Waglechner, Nicholas; Fourment, Mathieu; Forrest, Stephen A; Klunk, Jennifer; Schuenemann, Verena J; Poinar, Debi; Kuch, Melanie; Golding, G Brian; Dutour, Olivier; Keim, Paul; Wagner, David M; Holmes, Edward C

    2016-01-01

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

  8. Opposing roles for interferon regulatory factor-3 (IRF-3 and type I interferon signaling during plague.

    Directory of Open Access Journals (Sweden)

    Ami A Patel

    Full Text Available Type I interferons (IFN-I broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

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

    Directory of Open Access Journals (Sweden)

    Kiersten J. Kugeler

    2017-11-01

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

  10. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Background Plague is a rapidly progressing, serious illness in humans that is likely to be fatal if not treated. It remains a public health threat, especially in sub-Saharan Africa. In spite of plague's highly focal nature, a thorough ecological understanding of the general distribution pattern...... of plague across sub-Saharan Africa has not been established to date. In this study, we used human plague data from sub-Saharan Africa for 1970-2007 in an ecological niche modeling framework to explore the potential geographic distribution of plague and its ecological requirements across Africa. Results We...... predict a broad potential distributional area of plague occurrences across sub-Saharan Africa. General tests of model's transferability suggest that our model can anticipate the potential distribution of plague occurrences in Madagascar and northern Africa. However, generality and predictive ability tests...

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

    Science.gov (United States)

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

    2014-06-01

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

  13. Electroshock weapons can be lethal!

    Science.gov (United States)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

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

    Science.gov (United States)

    Sabbatani, S; Fiorino, S

    2009-12-01

    The Antonine Plague, which flared up during the reign of Marcus Aurelius from 165 AD and continued under the rule of his son Commodus, played such a major role that the pathocenosis in the Ancient World was changed. The spread of the epidemic was favoured by the occurrence of two military episodes in which Marcus Aurelius himself took part: the Parthian War in Mesopotamia and the wars against the Marcomanni in northeastern Italy, in Noricum and in Pannonia. Accounts of the clinical features of the epidemic are scant and disjointed, with the main source being Galen, who witnessed the plague. Unfortunately, the great physician provides us with only a brief presentation of the disease, his aim being to supply therapeutic approaches, thus passing over the accurate description of the disease symptoms. Although the reports of some clinical cases treated by Galen lead us to think that the Antonine plague was caused by smallpox, palaeopathological confirmation is lacking. Some archaeological evidence (such as terracotta finds) from Italy might reinforce this opinion. In these finds, some details can be observed, suggesting the artist's purpose to represent the classic smallpox pustules, typical signs of the disease. The extent of the epidemic has been extensively debated: the majority of authors agree that the impact of the plague was severe, influencing military conscription, the agricultural and urban economy, and depleting the coffers of the State. The Antonine plague affected ancient Roman traditions, also leaving a mark on artistic expression; a renewal of spirituality and religiousness was recorded. These events created the conditions for the spread of monotheistic religions, such as Mithraism and Christianity. This period, characterized by health, social and economic crises, paved the way for the entry into the Empire of neighbouring barbarian tribes and the recruitment of barbarian troops into the Roman army; these events particularly favoured the cultural and

  15. News Reports about Health: Between Heroes and Plagues

    Directory of Open Access Journals (Sweden)

    Acianela Montes de Oca

    2013-12-01

    Full Text Available This research characterizes news reports published in the health sections of two newspapers, El Nacional and El Universal, from 1996 to 2006 from the perspective of the myths. Mytheme analysis and rhetorical figures show that myths more frecuently used were The Hero, The Progress, The Plague and Panacea. From the analysis we concluded that the texts of the health sections of analyzed newspapers show a dangerous world (stalked by The Plague that only the Hero (the doctor can face. Science, technology, modernity, health, The Progress, Panacea, seem a gift rather than a human conquest. If we accept the premise that the myths act unify social representations and introduce a single meaning to the future, these stories express a look of helplessness and uncertainty in illness and risk.

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

    Science.gov (United States)

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

    1984-02-17

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

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

    International Nuclear Information System (INIS)

    Temiralieva, G.A.

    1977-01-01

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

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

    Science.gov (United States)

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

    2010-07-01

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

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

    Science.gov (United States)

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

    2012-01-01

    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.

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

    Science.gov (United States)

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

    2014-10-01

    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.

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

    Science.gov (United States)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Katharina S Kreppel

    2014-10-01

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

  3. Effect of lethal and sub-lethal concentrations of tobacco (Nicotiana ...

    African Journals Online (AJOL)

    Lethal and sub-lethal bioassays on Clarias gariepinus were conducted to evaluate the toxicity of tobacco (Nicotiana tobaccum) leaf dust on weight gain and haematological indices of Clarias gariepinus (mean weight 10.5±0.70g) in glass aquaria with aeration system. The concentrations used during the lethal exposure are: ...

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

    Directory of Open Access Journals (Sweden)

    Juan A Sánchez

    2010-05-01

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

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

    Science.gov (United States)

    Eads, David A.; Biggins, Dean E.

    2015-01-01

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

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

    Science.gov (United States)

    Eads, David A; Biggins, Dean E

    2015-08-01

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

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

    Science.gov (United States)

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

    2015-11-27

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

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

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

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

  9. Identification of duck plague virus by polymerase chain reaction

    Science.gov (United States)

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

    1999-01-01

    A polymerase chain reaction (PCR) assay was developed for detecting duck plague virus. A 765-bp EcoRI fragment cloned from the genome of the duck plague vaccine (DP-VAC) virus was sequenced for PCR primer development. The fragment sequence was found by GenBank alignment searches to be similar to the 3a?? ends of an undefined open reading frame and the gene for DNA polymerase protein in other herpesviruses. Three of four primer sets were found to be specific for the DP-VAC virus and 100% (7/7) of field isolates but did not amplify DNA from inclusion body disease of cranes virus. The specificity of one primer set was tested with genome templates from other avian herpesviruses, including those from a golden eagle, bald eagle, great horned owl, snowy owl, peregrine falcon, prairie falcon, pigeon, psittacine, and chicken (infectious laryngotracheitis), but amplicons were not produced. Hence, this PCR test is highly specific for duck plague virus DNA. Two primer sets were able to detect 1 fg of DNA from the duck plague vaccine strain, equivalent to five genome copies. In addition, the ratio of tissue culture infectious doses to genome copies of duck plague vaccine virus from infected duck embryo cells was determined to be 1:100, making the PCR assay 20 times more sensitive than tissue culture for detecting duck plague virus. The speed, sensitivity, and specificity of this PCR provide a greatly improved diagnostic and research tool for studying the epizootiology of duck plague. /// Se desarroll?? una prueba de reacci??n en cadena por la polimerasa para detectar el virus de la peste del pato. Un fragmento EcoRI de 765 pares de bases clonado del genoma del virus vacunal de la peste del pato fue secuenciado para la obtenci??n de los iniciadores de la prueba de la reacci??n en cadena por la polimerasa. En investigaciones de alineaci??n en el banco de genes ('GenBank') se encontr?? que la secuencia del fragmento era similar a los extremos 3a?? de un marco de lectura abierto

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  12. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

    1984-01-01

    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

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

    DEFF Research Database (Denmark)

    Davis, S; Trapman, P; Leirs, H

    2008-01-01

    . However, no natural examples have been reported. The central question of interest in percolation theory 4 , the possibility of an infinite connected cluster, corresponds in infectious disease to a positive probability of an epidemic. Archived records of plague (infection with Yersinia pestis....... Abundance thresholds are the theoretical basis for attempts to manage infectious disease by reducing the abundance of susceptibles, including vaccination and the culling of wildlife 6, 7, 8 . This first natural example of a percolation threshold in a disease system invites a re-appraisal of other invasion...

  14. Transporting Patients with Lethal Contagious Infections

    National Research Council Canada - National Science Library

    Swartz, Colleen

    2002-01-01

    .... The AIT is a unique military medical team capable of worldwide air evacuation and management of a limited number of patients who are potentially exposed to known and unknown lethal communicable...

  15. Experiences in therapy for lethal midline granuloma

    International Nuclear Information System (INIS)

    Tosaka, Kaoru; Ishikawa, Takeru

    1982-01-01

    Four cases of the lethal midline granuloma or malignant granuloma of the nose were treated by irradiation and chemotherapy, which are generally prescribed for malignant lymphomas. Clinical, histological and laboratory examination indicated that they were the lethal midline granuloma and clearly differentiated from Wegener's granulomatosis or malignant lymphoma. All of the cases exhibited primary remission. The four cases were observed up to 38, 22, 14, and 10 months since the beginning of the therapy, showing no local or general recurrence. (author)

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

    Directory of Open Access Journals (Sweden)

    Ayelet Zauberman

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

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

    Science.gov (United States)

    Lindler, Luther E

    2009-01-01

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

  18. Pattern and spatial distribution of plague in Lushoto, north-eastern ...

    African Journals Online (AJOL)

    A review of plague records from 1986 to 2002 and household interviews were carried out in the plague endemic villages to establish a pattern and spatial distribution of the disease in Lushoto district, Tanzania. Spatial data of households and village centres were collected and mapped using a hand held Global Positioning ...

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Assessing plague risk and presence through surveys of small mammal flea communities

    Science.gov (United States)

    M. M. Friggens; P. L. Ford; R. R. Parmenter; M. Boyden; K. Gage

    2011-01-01

    Plague, caused by the bacterium Yersinia pestis, remains a threat to human and wildlife populations in the Western United States (Gage and Kosoy 2005). Several rodent species have been implicated as important maintenance hosts in the U.S., including Peromyscus maniculatus and Dipodomys spp. Fleas are a critical component of plague foci (Gage and Kosoy 2005)....

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

    Schmid, Boris V; Büntgen, Ulf; Easterday, W Ryan; Ginzler, Christian; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr

    2015-03-10

    The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

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

    Science.gov (United States)

    Büntgen, Ulf; Easterday, W. Ryan; Ginzler, Christian; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr.

    2015-01-01

    The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe. PMID:25713390

  5. Lethality Index 2008-2014: Less shootings, same lethality, more opacity

    Directory of Open Access Journals (Sweden)

    Carlos Silva Forné

    2017-11-01

    Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

  6. Host stress and immune responses during aerosol challenge of Brown Norway rats with Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Susan T Gater

    2012-11-01

    Full Text Available Inhalation exposure models are becoming the preferred method for the comparative study of respiratory infectious diseases due to their resemblance to the natural route of infection. To enable precise delivery of pathogen to the lower respiratory tract in a manner that imposes minimal biosafety risk, nose-only exposure systems have been developed. Early inhalation exposure technology for infectious disease research grew out of technology used in asthma research where predominantly the Collison nebulizer is used to generate an aerosol by beating a liquid sample against glass. Although infectious aerosol droplets of 1-5µm in size can be generated, the Collison often causes loss of viability. In this work, we evaluate a gentler method for aerosolization of living cells and describe the use of the Sparging Liquid Aerosol Generator (SLAG in a rat pneumonic plague model. The SLAG creates aerosols by continuous dripping of liquid sample on a porous metal disc. We show the generation of 0.5 to 1µm Y. pestis aerosol particles using the SLAG with spray factors typically ranging from 10-7 to 10-8 with no detectable loss of bacterial viability. Delivery of these infectious particles via nose-only exposure led to the rapid development of lethal pneumonic plague. Further, we evaluated the effect of restraint-stress imposed by the nose-only exposure chamber on early inflammatory responses and bacterial deposition. Elevated serum corticosterone which peaked at 2 hrs post-procedure indicated the animals experienced stress as a result of restraint in the nose-only chamber. However, we observed no correlation between elevated corticosterone and the amount of bacterial deposition or inflammation in the lungs. Together these data demonstrate the utility of the SLAG and the nose-only chamber for aerosol challenge of rodents by Y. pestis.

  7. Parental response to severe or lethal prenatal diagnosis

    DEFF Research Database (Denmark)

    Lou, Stina; Jensen, Lotte Groth; Petersen, Olav Bjørn

    2017-01-01

    Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify and synt......Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify...... and synthesize the qualitative evidence regarding prospective parents’ responses to such prenatal diagnoses. Methods Following PRISMA guidelines, four databases were systematically searched and 28 studies met the inclusion criteria. Thematic analysis guided data extraction and synthesis of findings. The CERQual....... Prospective parents who continued the pregnancy wished to be acknowledged as parents, and engaged in planning to obtain a sense of meaning and control. Selective disclosure and concerns about negative responses were issues both for the parents who terminated and those who continued a pregnancy. Conclusion...

  8. A bibliography of literature pertaining to plague (Yersinia pestis)

    Science.gov (United States)

    Ellison, Laura E.; Frank, Megan K. Eberhardt

    2011-01-01

    Plague is an acute and often fatal zoonotic disease caused by the bacterium Yersinia pestis. Y. pestis mainly cycles between small mammals and their fleas; however, it has the potential to infect humans and frequently causes fatalities if left untreated. It is often considered a disease of the past; however, since the late 1800s, plagueis geographic range has expanded greatly, posing new threats in previously unaffected regions of the world, including the Western United States. A literature search was conducted using Internet resources and databases. The keywords chosen for the searches included plague, Yersinia pestis, management, control, wildlife, prairie dogs, fleas, North America, and mammals. Keywords were used alone or in combination with the other terms. Although this search pertains mostly to North America, citations were included from the international research community, as well. Databases and search engines used included Google (http://www.google.com), Google Scholar (http://scholar.google.com), SciVerse Scopus (http://www.scopus.com), ISI Web of Knowledge (http://apps.isiknowledge.com), and the USGS Library's Digital Desktop (http://library.usgs.gov). The literature-cited sections of manuscripts obtained from keyword searches were cross-referenced to identify additional citations or gray literature that was missed by the Internet search engines. This Open-File Report, published as an Internet-accessible bibliography, is intended to be periodically updated with new citations or older references that may have been missed during this compilation. Hence, the authors would be grateful to receive notice of any new or old papers that the audience (users) think need to be included.

  9. The Stone Age Plague and Its Persistence in Eurasia.

    Science.gov (United States)

    Andrades Valtueña, Aida; Mittnik, Alissa; Key, Felix M; Haak, Wolfgang; Allmäe, Raili; Belinskij, Andrej; Daubaras, Mantas; Feldman, Michal; Jankauskas, Rimantas; Janković, Ivor; Massy, Ken; Novak, Mario; Pfrengle, Saskia; Reinhold, Sabine; Šlaus, Mario; Spyrou, Maria A; Szécsényi-Nagy, Anna; Tõrv, Mari; Hansen, Svend; Bos, Kirsten I; Stockhammer, Philipp W; Herbig, Alexander; Krause, Johannes

    2017-12-04

    Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6 th century AD, which persisted until the 8 th century [1]; the renowned Black Death of the 14 th century [2, 3], with recurrent outbreaks until the 18 th century [4]; and the most recent 19 th century pandemic, in which Y. pestis spread worldwide [5] and became endemic in several regions [6]. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic [7]. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange [8, 9]. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Rigobert C. Ngeleja

    2017-01-01

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

  11. Influence of human activity patterns on epidemiology of plague in Western Usambara Mountains, Tanzania.

    Science.gov (United States)

    Hubeau, Marianne; Gulinck, Hubert; Kimaro, Didas N; Hieronimo, Proches; Meliyo, Joel

    2014-07-01

    Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs to broaden its scope and formulate new hypotheses. This study was carried out to establish relationships between the nature and the spatial extent of selected human activities on one hand, and the reported plague cases on the other hand. Three outdoor activities namely, fetching water, collecting firewood and going to the market, were selected. Through enquiries the activity patterns related to these activities were mapped in 14 villages. Standard deviation ellipses represent the extent of action spaces. Over 130 activity types were identified and listed. Of these, fetching water, collecting firewood and going to the market were used for further analysis. The results indicate a significant correlation between the plague frequency and the size of these action spaces. Different characteristics of land use and related human activities were correlated with the plague frequency at village and hamlet levels. Significant relationships were found between plague frequency and specific sources of firewood and water, and specific market places.

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

    Science.gov (United States)

    2015-11-01

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

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

    Science.gov (United States)

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

    2015-02-07

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Pribyl, Kathleen

    2017-04-01

    The climatological triggers of major plague outbreaks in late medieval and early modern Europe remain unclear; recent studies have been inconclusive. Plague is primarily a rodent disease and due to the involvement of rodent hosts and insect vectors, the epidemiology of plague is complicated, but research on outbreaks in the Third Pandemic, which began in the late nineteenth century, has shown that in central and eastern Asia plague is linked to specific meteorological conditions. The disease adapts to a varied spectrum of ecological and climatological settings, which influence the development of plague waves, and due to Europe's geographical diversity, this paper focuses on one region, England, in its search for meteorological parameters contributing to plague outbreaks. The study period of this paper is defined by the arrival of Yersinia pestis in the British Isles in 1348 and the end of the fifteenth century. During this time, England's population dynamics were mortality-driven due to recurrent epidemic disease; and public health measures, such as quarantining, had not yet been introduced, hence the influence of social factors on the formation of major plague waves was very limited. The geographical and temporal focus of this study allows for the combination of the series of English major plague outbreaks, verified in the original texts, with the high-quality climate reconstructions based on both documentary sources and proxy data available for this region. The detailed analysis of the mechanisms contributing to English plague waves presented in this paper, reveals a complex interplay of time-lag responses and concurrent conditions involving temperature and precipitation parameters.

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

    Science.gov (United States)

    Hernández-Mansilla, José Miguel

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    Mendez Buenaventura, L.

    1995-01-01

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

  18. Plague in Egypt: Disease biology, history and contemporary analysis: A minireview

    Directory of Open Access Journals (Sweden)

    Wael M. Lotfy

    2015-07-01

    Full Text Available Plague is a zoonotic disease with a high mortality rate in humans. Unfortunately, it is still endemic in some parts of the world. Also, natural foci of the disease are still found in some countries. Thus, there may be a risk of global plague re-emergence. This work reviews plague biology, history of major outbreaks, and threats of disease re-emergence in Egypt. Based on the suspected presence of potential natural foci in the country, the global climate change, and the threat posed by some neighbouring countries disease re-emergence in Egypt should not be excluded. The country is in need for implementation of some preventive measures.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Florent Sebbane

    2010-12-01

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

  1. Genetics Home Reference: Amish lethal microcephaly

    Science.gov (United States)

    ... 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why are some genetic ... gene cause Amish lethal microcephaly . The SLC25A19 gene provides instructions for ...

  2. The evolution of lethal intergroup violence

    OpenAIRE

    Kelly, Raymond C.

    2005-01-01

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  3. The evolution of lethal intergroup violence.

    Science.gov (United States)

    Kelly, Raymond C

    2005-10-25

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  4. A new lethal sclerosing bone dysplasia

    International Nuclear Information System (INIS)

    Kingston, H.M.; Freeman, J.S.; Hall, C.M.

    1991-01-01

    A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology. (orig.)

  5. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    Directory of Open Access Journals (Sweden)

    Miriam S. N. Hohmann

    2013-01-01

    Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

  6. Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

    Science.gov (United States)

    Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

    2015-01-01

    Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

  7. [The plague: A disease that is still haunting our collective memory].

    Science.gov (United States)

    Peiffer-Smadja, N; Thomas, M

    2017-06-01

    Although the plague has practically disappeared from Europe since the beginning of the 20th century, it is still present in everyone's memory. Owing to three pandemics, it has left an indelible mark on mankind and has given rise to many popular phrases, paintings, books or more recently movies and video games. After a brief description of the plague as a disease, we will try to trace the history of the plague through some of the works of art it inspired and then to show how the plague is still haunting our collective memory. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

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

    Centers for Disease Control (CDC) Podcasts

    Reginald Tucker reads an abridged version of the Emerging Infectious Diseases’ historical Review, Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th -Centruy Alghero, Sardinia.

  9. Epidemiology of Human Plague in the United States, 1900–2012

    Centers for Disease Control (CDC) Podcasts

    2015-02-23

    Dr. Kiersten Kugeler discusses the Epidemiology of Human Plague in the United States.  Created: 2/23/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 2/23/2015.

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

    Directory of Open Access Journals (Sweden)

    Françoise Guinet

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-08-12

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

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

    OpenAIRE

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2016-05-31

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

  15. A Field Study of Plague and Tularemia in Rodents, Western Iran.

    Science.gov (United States)

    Mostafavi, Ehsan; Shahraki, Abdolrazagh Hashemi; Japoni-Nejad, Alireza; Esmaeili, Saber; Darvish, Jamshid; Sedaghat, Mohammad Mehdi; Mohammadi, Ali; Mohammadi, Zeinolabedin; Mahmoudi, Ahmad; Pourhossein, Behzad; Ghasemi, Ahmad; Gyuranecz, Miklós; Carniel, Elisabeth

    2017-04-01

    Kurdistan Province in Iran is a historical focus for plague and tularemia. This study aimed at assessing the current status of these two foci by studying their rodent reservoirs. Rodents were trapped and their ectoparasites were collected. The genus and species of both rodents and ectoparasites were determined. Serological analyses of rodent blood samples were done by enzyme-linked immunosorbent assay for plague and by standard tube agglutination assay for tularemia. Rodent spleen samples were subjected to bacterial culture, microscopic examination, and real-time PCR to search for active plague or tularemia infection. During this study, 245 rodents were trapped, of which the most abundant genera were Apodemus (40%), Mus (24.49%), and Meriones (12.65%). One hundred fifty-three fleas, 37 mites, and 54 ticks were collected on these rodents. The results of all direct and indirect tests were negative for plague. Serological tests were positive for tularemia in 4.8% of trapped rodents. This study is the first report on the presence of tularemia infection in rodents in Western Iran. Since Meriones persicus is a known reservoir for plague and tularemia, and this rodent carried plague and tularemia vectors in Marivan and Sanandaj districts, there is a real potential for the occurrence of these two diseases in this region.

  16. Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania.

    Science.gov (United States)

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

    2014-07-01

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto District. Data were collected in three landscapes differing in plague incidence. Field survey coupled with Geographic Information System (GIS) and physical sample collections were used to collect data in wet (April to June 2012) and dry (August to October 2012) seasons. Data analysis was done using GIS, one-way ANOVA and nonparametric statistical tools. The degree of spatial co-occurrence of potential disease vectors (fleas) and humans in Lushoto focus differs significantly (p ≤ 0.05) among the selected landscapes, and in both seasons. This trend gives a coarse indication of the possible association of the plague outbreaks and the human frequencies of contacting environments with fleas. The study suggests that plague surveillance and control programmes at landscape scale should consider the existence of plague vector contagion risk gradient from high to low incidence landscapes due to human presence and intensity of activities.

  17. Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-03

    Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

  18. Potential role of viruses in white plague coral disease.

    Science.gov (United States)

    Soffer, Nitzan; Brandt, Marilyn E; Correa, Adrienne M S; Smith, Tyler B; Thurber, Rebecca Vega

    2014-02-01

    White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.

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

    Science.gov (United States)

    Ossa, Jorge E.

    1975-01-01

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

  20. Lethal neonatal short-limbed dwarfism

    International Nuclear Information System (INIS)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee

    1986-01-01

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  1. Lethal neonatal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee [Catholic Medical College, Seoul (Korea, Republic of)

    1986-02-15

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  2. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh

    2015-01-01

    in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

  3. Lethal midline granuloma syndrome: a diagnostic dilemma

    International Nuclear Information System (INIS)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle; Oliveira, Ana Luiza Vianna Sobral de Magalhaes; Marchon Junior, Joao Luiz

    2012-01-01

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  4. Lethal Interpersonal Violence in the Middle Pleistocene

    OpenAIRE

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-P?rez, Ana; Pablos, Adri?n; Mart?nez, Ignacio; Quam, Rolf M.; G?mez-Olivencia, Asier; Berm?dez de Castro, Jos? Mar?a; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force ...

  5. Lethal midline granuloma syndrome: a diagnostic dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle [Radiology, Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ (Brazil); Oliveira, Ana Luiza Vianna Sobral de Magalhaes [Resident of Medical Practice, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil); Marchon Junior, Joao Luiz [Unit of Computed Tomography, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil)

    2012-11-15

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  6. Lethal interpersonal violence in the Middle Pleistocene.

    Directory of Open Access Journals (Sweden)

    Nohemi Sala

    Full Text Available Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  7. Lethal interpersonal violence in the Middle Pleistocene.

    Science.gov (United States)

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

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

    Science.gov (United States)

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

    2016-07-01

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

  9. Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis.

    Directory of Open Access Journals (Sweden)

    Rasha Hammamieh

    Full Text Available Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre-symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential.

  10. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

    Science.gov (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-11-07

    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  11. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  12. Sylvatic plague vaccine partially protects prairie dogs (Cynomys spp.) in field trials

    Science.gov (United States)

    Rocke, Tonie E.; Tripp, Daniel W.; Russell, Robin E.; Abbott, Rachel C.; Richgels, Katherine; Matchett, Marc R.; Biggins, Dean E.; Griebel, Randall; Schroeder, Greg; Grassel, Shaun M.; Pipkin, David R.; Cordova, Jennifer; Kavalunas, Adam; Maxfield, Brian; Boulerice, Jesse; Miller, Michael W.

    2017-01-01

    Sylvatic plague, caused by Yersinia pestis, frequently afflicts prairie dogs (Cynomys spp.), causing population declines and local extirpations. We tested the effectiveness of bait-delivered sylvatic plague vaccine (SPV) in prairie dog colonies on 29 paired placebo and treatment plots (1–59 ha in size; average 16.9 ha) in 7 western states from 2013 to 2015. We compared relative abundance (using catch per unit effort (CPUE) as an index) and apparent survival of prairie dogs on 26 of the 29 paired plots, 12 with confirmed or suspected plague (Y. pestis positive carcasses or fleas). Even though plague mortality occurred in prairie dogs on vaccine plots, SPV treatment had an overall positive effect on CPUE in all three years, regardless of plague status. Odds of capturing a unique animal were 1.10 (95% confidence interval [C.I.] 1.02–1.19) times higher per trap day on vaccine-treated plots than placebo plots in 2013, 1.47 (95% C.I. 1.41–1.52) times higher in 2014 and 1.19 (95% C.I. 1.13–1.25) times higher in 2015. On pairs where plague occurred, odds of apparent survival were 1.76 (95% Bayesian credible interval [B.C.I.] 1.28–2.43) times higher on vaccine plots than placebo plots for adults and 2.41 (95% B.C.I. 1.72–3.38) times higher for juveniles. Our results provide evidence that consumption of vaccine-laden baits can protect prairie dogs against plague; however, further evaluation and refinement are needed to optimize SPV use as a management tool.

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

    Directory of Open Access Journals (Sweden)

    Egan Joseph R

    2010-10-01

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

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

    Science.gov (United States)

    Whittles, Lilith K; Didelot, Xavier

    2016-05-11

    Plague, caused by the bacterium Yersinia pestis, is one of the deadliest infectious diseases in human history, and still causes worrying outbreaks in Africa and South America. Despite the historical and current importance of plague, several questions remain unanswered concerning its transmission routes and infection risk factors. The plague outbreak that started in September 1665 in the Derbyshire village of Eyam claimed 257 lives over 14 months, wiping out entire families. Since previous attempts at modelling the Eyam plague, new data have been unearthed from parish records revealing a much more complete record of the disease. Using a stochastic compartmental model and Bayesian analytical methods, we found that both rodent-to-human and human-to-human transmission played an important role in spreading the infection, and that they accounted, respectively, for a quarter and three-quarters of all infections, with a statistically significant seasonality effect. We also found that the force of infection was stronger for infectious individuals living in the same household compared with the rest of the village. Poverty significantly increased the risk of disease, whereas adulthood decreased the risk. These results on the Eyam outbreak contribute to the current debate on the relative importance of plague transmission routes. © 2016 The Authors.

  15. Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

    Science.gov (United States)

    Miarinjara, Adélaïde; Boyer, Sébastien

    2016-02-01

    Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Hang'ombe Bernard M

    2012-01-01

    Full Text Available Abstract Background Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. Findings Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02% for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. Conclusions We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia.

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

    Directory of Open Access Journals (Sweden)

    Kausrud Kyrre

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Prodanov Jasna

    2002-01-01

    Full Text Available Piglets infected with the conventional swine plague virus as a result of secondary bacterial infections sometimes show an insufficiently clear clinical and pathoanatomical picture, which is why the very procedure of diagnosis is complex and the final diagnosis unreliable. That is why these investigations were aimed at examining the presence of bacterial microflora in diseased and dead pilgets which were found to have the viral antigen for CSP using the fluorescent antibody technique, in cases where the pathomorphological finding was not characteristic for conventional swine plague. Autopsies of dead piglets most often showed changes in the digestive tract and lungs, with resulting technopathy and diseases of infective nature. Such findings on knowledge of a present bacterial microflora are especially important in cases when conventional swine plague is controlled on farms and an announcement that the disease has been contained is in the offing.

  20. Seroprevalence of hantavirus and Yersinia pestis antibodies in professionals from the Plague Control Program

    Directory of Open Access Journals (Sweden)

    Erika de Cassia Vieira da Costa

    2013-07-01

    Full Text Available Introduction Professionals who handle rodents in the field and in the laboratory are at risk of infection by the microorganisms harbored by these animals. Methods Serum samples from professionals involved in rodent and Yersinia pestis handling in field or laboratory work were analyzed to determine hantavirus and plague seroprevalence and to establish a relationship between these activities and reports of illnesses. Results Two individuals had antibodies against hantavirus, and two harbored antibodies against the plague; none of the individuals had experienced an illness related to their duties. Conclusions These results confirm the risks of hantavirus- and plague-related field and laboratory activities and the importance of protective measures for such work.

  1. Demographic and spatio-temporal variation in human plague at a persistent focus in Tanzania

    DEFF Research Database (Denmark)

    Davis, S; Makundi, R H; Machang'u, R S

    2006-01-01

    Human plague in the Western Usambara Mountains in Tanzania has been a public health problem since the first outbreak in 1980. The wildlife reservoir is unknown and eradication measures that have proved effective elsewhere in Tanzania appear to fail in this region. We use census data from 2002...... and hospital records kept since 1986 to describe the temporal, spatial and demographic variation in human plague. A seasonal peak in cases occurs from December to February with the numbers of cases during this peak varying between 0 and 1150. Variation in incidence, calculated for each village as the mean...... number of cases per thousand inhabitants per year, indicates that human plague is concentrated around a group of three neighbouring, relatively isolated, high-altitude villages; Nywelo, Madala and Gologolo. However, there was no evidence that these villages were acting as a source of infection...

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

    Science.gov (United States)

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

    2016-12-01

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

  3. [A NATURAL PLAGUE FOCUS. IN GORNYI ALTAI: FORMATION, DEVELOPMENT, AND FUNCTIONING].

    Science.gov (United States)

    Korzun, V M; Balakhoiov, S V; Chpanin, E V; Denisov, A V; Mikhailov, E P; Mischenko, A J; Yarygina, M B; Rozhdestvensky, E N; Fomina, L A

    2016-01-01

    The paper gives the results of analyzing the data of long-term studies of the natural focal pattern of plague in the Gornyi Altai natural focus. It describes a wide range of biological processes occurring in the focus and shows the most important patterns of its functioning as a complex multilevel ecological system. The key features of the formation of the focus have been revealed. The plague focus in South-Western Altai has formed relatively, recently, about half a century ago, then it has intensively developed and its enzootic area and the activity of epizootic manifestations have considerably increased. This process is due to the space-time transformations of the basic ecological and population characteristics of Pallas' pika (Ochotoma pallasi), the principal vector of the pathogen of plague and fleas parasitizing the mammal, which is in turn related to the aridization of mountain steppes in South-Western Altai.

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

    Science.gov (United States)

    Suntsov, V V

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Mafart, B; Brisou, P; Bertherat, E

    2004-11-01

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

  7. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

    Science.gov (United States)

    Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

    2006-09-01

    Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

  8. Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

    Science.gov (United States)

    Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

    2004-01-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

  9. Potentially lethal damage and its repair

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1989-01-01

    Two forms termed fast-and slow-potentially lethal lethal damage (PLD) are introduced and discussed. The effect on the survival of x-irradiated Chinese hamster cells (V79) of two different post-treatments is examined in plateau- and in log-phases of growth. The postirradiation treatments used : a) incubation in hypertonic solution, and b) incubation in conditioned medium obtained from plateau-phase. Similar reduction in survival was caused by postirradiation treatment with hypertonic phosphate buffered saline, and similar increased in survival was effected by treatment in conditioned medium in plateau- and in log-phases cells. However, repair of PLD sensitive to hypertonic treatment was faster (half time, 5-10 min)(f-PLD repair) and independent from the repair of PLD (half time, 1-2 hour)(s-PLD repair) observed in conditioned medium. The results indicate the induction of two forms of PLD by radiation. Induction of both PLD was found to decrease with increasing LET of the radiation used. Identification of the molecular processes underlying repair and fixation of PLD is a task of particular interest, since it may allow replacement of a phenomenological definition with a molecular definition. Evidence is reviewed indicating the DNA double strand breaks (directly or indirectly induced) may be the DNA lesions underlying PLD. (author)

  10. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error

    OpenAIRE

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M

    2014-01-01

    Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Methods: Prostatectom...

  11. Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody

    Science.gov (United States)

    2016-07-11

    were 49   identified and enrolled in VRC200 clinical trial #NCT00067054 after giving signed 50   informed consent . Peripheral blood mononuclear...illness 56   when administered one day after lethal challenge. Treatment with a single human 57   mAb suggests a simplified therapeutic strategy for...efforts to simplify the ZMapp regimen to contain fewer mAbs have not been successful in 75   the macaque EVD model (7). We sought to isolate

  12. Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

    Science.gov (United States)

    2007-10-01

    Sarin 5a. CONTRACT NUMBER Intoxication in the Guinea Pig 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Koplovitz, I and...efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs . Male animals were challenged subcutaneously (s.c.) with 2 LD50s...oximes that are readily able to enter the brain. 15. SUBJECT TERMS oximes, brain, sarin, reactivation, nerve agents, guinea pigs 16. SECURITY

  13. Lethal domestic violence in eastern North Carolina.

    Science.gov (United States)

    Gilliland, M G; Spence, P R; Spence, R L

    2000-01-01

    Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

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

    Directory of Open Access Journals (Sweden)

    Christakos George

    2006-03-01

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

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

    Science.gov (United States)

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

    2017-06-01

    Bubonic plague has caused three deadly pandemics in human history: from the mid-sixth to mid-eighth century, from the mid-fourteenth to the mid-eighteenth century and from the end of the nineteenth until the mid-twentieth century. Between the second and the third pandemics, plague was causing sporadic outbreaks in only a few countries in the Middle East, including Egypt. Little is known about this historical phase of plague, even though it represents the temporal, geographical and phylogenetic transition between the second and third pandemics. Here we analysed in detail an outbreak of plague that took place in Cairo in 1801, and for which epidemiological data are uniquely available thanks to the presence of medical officers accompanying the Napoleonic expedition into Egypt at that time. We propose a new stochastic model describing how bubonic plague outbreaks unfold in both rat and human populations, and perform Bayesian inference under this model using a particle Markov chain Monte Carlo. Rat carcasses were estimated to be infectious for approximately 4 days after death, which is in good agreement with local observations on the survival of infectious rat fleas. The estimated transmission rate between rats implies a basic reproduction number R 0 of approximately 3, causing the collapse of the rat population in approximately 100 days. Simultaneously, the force of infection exerted by each infected rat carcass onto the human population increases progressively by more than an order of magnitude. We also considered human-to-human transmission via pneumonic plague or human specific vectors, but found this route to account for only a small fraction of cases and to be significantly below the threshold required to sustain an outbreak. © 2017 The Author(s).

  16. [Preventive measures against plague and the control of Chinese coolies in colonial Korea].

    Science.gov (United States)

    Kim, Youngsoo

    2014-12-01

    This paper aims to examine the preventive measures taken against the plague in colonial Korea, particularly as applied to the control of Chinese coolies in 1911, soon after the annexation. The Government General of Korea began preventive measures with a train quarantine in Shin'uiju and Incheon in response to the spread of the plague to the Southern Manchuria. Shin' uiju had become urbanized due the development of the transportation network, and the seaport of Incheon was the major hub for traffic with China. Examining the transportation routes for the entry and exit of Chinese to and from Korea makes clear the reason why the Korea Government General initiated preventive measures in mid-January, 1911. The Government General of Korea tried to block the entry of Chinese through the land border crossing with China and through ports of entry, primarily Incheon. During the implementation of the preventive measures, quarantine facilities were built, including a quarantine station and isolation facility in Incheon. It was also needed to investigate the population and residential locations of Chinese in Korea to prevent the spread of plague. A certificate of residence was issued to all Chinese in Korea, which they needed to carry when they travelled. The preventive measures against plague which broke out in Manchuria were removed gradually. However, there was no specific measures against Chinese coolies, those who had migrated from China to work in the spring in Korea. Still the Government General of Korea had doubt about an infection of the respiratory system. As a result, the labor market in colonial Korea underwent changes in this period. The Government General recruited Korean laborers, instead of Chinese coolies whose employment had been planned. This move explains the Government General's strong preventive measures against plague and uncertainty in the route of plague infection, which influenced subsequent regulations on the prohibition of Chinese coolies working on

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

    Science.gov (United States)

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

    2016-02-01

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

  18. Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

    Science.gov (United States)

    Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E.

    2011-01-01

    Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations 10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

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

    Science.gov (United States)

    2014-01-01

    Background This qualitative investigation was conducted to determine the socio-epidemiological factors related to the plague outbreak (2002) in Himachal Pradesh (HP), India. Methods The data for socio-epidemiological factors related to the plague outbreak (2002) in HP was obtained from residents through 150 in-depth Interviews (IDI) and 30 Focus Group Discussions (FGD) during six visits (from May 2011 to April 2012) by the research team. Natives, health officials and the nomadic population were interviewed. According to their opinion and viewpoints data was collected and their lifestyle and hunting practices were studied in detail. Tape recorders were used during various FGDs and IDIs. The interviews and FGDs were later transcribed and coded. In-depth analysis of the recorded data was done using an inductive thematic analysis approach. Results The study reports that the outbreak in 2002 in a few villages of Himachal Pradesh was that of plague and it occurred by the contact of an index case with wild animals after hunting and de-skinning. The first wave of plague transmission which took 16 lives of residents was followed by a second wave of transmission in a ward of a tertiary care hospital where one visitor acquired it from relatives of the index case and succumbed. The life-style practices of residents (hunting behavior, long stay in caves and jungles, overcrowding in houses, poor hygiene and sanitation, belief in ‘God’ and faith healers for cure of diseases) was optimal for the occurrence and rapid spread of such a communicable disease. The man-rodent contact is intensified due to the practice of hunting in such a rodent-ridden environment. The residents harbor a strong belief that plague occurs due to the wrath of gods. Various un-reported outbreaks of plague were also observed by officials, residents and old folk. The persistence of plague in HP is favoured by its hilly terrain, inaccessible areas, inclement weather (snow) in winters, unhygienic lifestyle

  20. Spatial distribution patterns of plague hosts : point pattern analysis of the burrows of great gerbils in Kazakhstan

    NARCIS (Netherlands)

    Wilschut, Liesbeth I; Laudisoit, Anne; Hughes, Nelika K; Addink, Elisabeth A; de Jong, Steven M; Heesterbeek, Hans A P; Reijniers, Jonas; Eagle, Sally; Dubyanskiy, Vladimir M; Begon, Mike

    AIM: The spatial structure of a population can strongly influence the dynamics of infectious diseases, yet rarely is the underlying structure quantified. A case in point is plague, an infectious zoonotic disease caused by the bacterium Yersinia pestis. Plague dynamics within the Central Asian desert

  1. [Risk assessments and control strategies of plague in five key surveillance counties, Zhejiang province].

    Science.gov (United States)

    Shi, Guoxiang; Ju, Cheng; Zhang, Rong; Zhang, Zheng; Sun, Jimin; Wang, Miaoruo; Zhang, Xiaohe; Ye, Xianming; Zhu, Zhihong; Xing, Jianguang; Liao, Xiaowei; Chen, Zhiping

    2015-10-01

    To analyze the epidemiology data on plague in five counties in Zhejiang province and to evaluate the risk of plague in theses areas. We selected five monitoring stations as a risk assessment (Qingyuan county, Longquan city, Yiwu city, Wencheng county, and Ruian city) in Zhejiang province where the plague epidemic more serious in the history. At least one constant site and 1-4 variable sites where plague occurred in history were selected for monitoring. We collected the five counties (cities) surveillance data of indoor rat density, indoor Rattus flavipectus density, the Xenopsylla cheopis index of rat, the Xenopsylla cheopis index of Rattus flavipectus in 1995-2014. Isolation of Yersinia pestis was conducted among 171,201 liver samples and F1 antibody were detected among 228,775 serum samples. Risk matrix, Borda count method, and Delphi approach were conducted to assess risk of the plague of five counties (cities) in Zhejiang province. Indoor rat density in Qingyuan county, Longquan city, Yiwu city, Wencheng county, Ruian city was 1.58%-5.50%, 1.13%-9.76%, 0.56%-3.67%, 2.83%-16.08%, 7.16%-15.96%, respectively; Indoor Rattus flavipectus density of five counties (cities) was 0.08%-2.23%, 0-2.02%, 0-0.54%, 0.71%-5.58%, 0.55%-4.92%, respectively. The Xenopsylla cheopis index of rat in Qingyuan county and Wencheng county was 0.011-0.500 and 0.015-0.227, respectively; The Xenopsylla cheopis index of Rattus flavipectus of Qingyuan county and Wencheng county was 0.119-3.412 and 0.100-1.430, respectively; Ruian City and Yiwu city cannot collected Xenopsylla cheopis, Long quan city only collected the Xenopsylla cheopis index of rat in the five years. Yersinia pestis were not isolated in five counties (cities).There were 3 Apodemus agrarius samples positive of plague F1 antibody test, in Longquan city and Yiwu city in 2005. Borda count method to assess the Longquan city, Yiwu (Borda point were both 321) plague risk was higher than three other regions; Delphi approach to

  2. Computed tomography of lethal medline granuloma

    International Nuclear Information System (INIS)

    Lee, Ho Suk; Kim, Tae Ho; Suh, Kyung Jin; Kim, Tae Hun; Kim, Yong Joo; Kang, Duk Sik

    1991-01-01

    In order to clarify the CT findings of lethal midline granuloma (LMG) diagnosed clinically or histopathologically, the authors retrospectively analyzed 12 patients who were seen at Kyungpook National University Hospital from February 1985 to August 1989. CT showed nasal mucosal thickening and / or soft tissue mass (9 case), spreading of the lesions along the facial subcutaneous fat plane (8 cases), invasion into the paranasal sinuses (5 cases), bone destruction (5 cases), nasopharyngeal mass lesion (2 cases), and extension of the lesion into the infratemporal fossa (1 case). In spite of the fact that CT does not make definitive diagnosis of LMG, it permits evaluation of the extent of the lesion, detection of the combined lesion, differential diagnosis, and close monitoring of its evolution under treatment

  3. Gluconeogenesis in lethally X-irradiated rats

    International Nuclear Information System (INIS)

    Paulikova, E.; Ahlers, I.; Praslicka, M.

    1983-01-01

    The in vivo incorporation of U- 14 C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of 14 C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis. (author)

  4. Gluconeogenesis in lethally X-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Paulikova, E.; Ahlers, I.; Praslicka, M. (Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie)

    1983-02-01

    The in vivo incorporation of U-/sup 14/C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of /sup 14/C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis.

  5. Ants defend aphids against lethal disease

    Science.gov (United States)

    Nielsen, Charlotte; Agrawal, Anurag A.; Hajek, Ann E.

    2010-01-01

    Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies. PMID:19923138

  6. Lethal photosensitization of biofilm-grown bacteria

    Science.gov (United States)

    Wilson, Michael

    1997-12-01

    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  7. Tityus serrulatus venom--A lethal cocktail.

    Science.gov (United States)

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    African Journals Online (AJOL)

    These findings suggest that land use factors have a major influence on rodent flea abundance which can be taken as a proxy for plague infection risk. The results further point to the need for a comprehensive package that includes land tillage and crop type considerations on one hand and the associated human activities on ...

  9. Evaluation of systemic insecticides mixed in rodenticide baits for plague vector control

    DEFF Research Database (Denmark)

    Larsen, Kim Søholt; Lodal, Jens

    1997-01-01

    Rodenticide baits containing systemic insecticides were evaluated in the laboratory for their palatability to the house rat Rattus rattus and for their toxicity against the oriental rat flea Xenopsylla cheopis - both animals are important Vectors of plague in Africa. The test bait and a non...

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

    International Nuclear Information System (INIS)

    Mangiarotti, Sylvain

    2015-01-01

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

  11. Ovid’s Aeginetan plague and the metamorphosis of the Georgics

    NARCIS (Netherlands)

    Heerink, M.A.J.

    2011-01-01

    The influence of the ancient literary tradition upon the Georgics is as broad as it is profound , but in Virgil’s highly allusive didactic poem, the description of the Noric cattle plague at the end of Georgics 3 holds a unique position. As R.F. THOMAS comments, "nowhere else does Virgil draw so

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

    DEFF Research Database (Denmark)

    Koch, Christian

    1998-01-01

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

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

    Science.gov (United States)

    Mize, Erica L; Britten, Hugh B

    2016-02-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  16. Remote sensing for landscape epidemiology : spatial analysis of plague hosts in Kazakhstan

    NARCIS (Netherlands)

    Wilschut, L.I.

    2015-01-01

    The spatial distribution of hosts is a crucial aspect for the understanding of infectious disease dynamics. In Kazakhstan, the great gerbil (Rhombomys opimus) is the main host for plague (Yersinia pestis infection) and poses a public health threat, yet their spatial distribution is unknown. Great

  17. Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague

    Centers for Disease Control (CDC) Podcasts

    2014-11-18

    Sarah Gregory reads an abridged version of the essay, Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague.  Created: 11/18/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/20/2014.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Pradel

    2014-03-01

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

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

    Science.gov (United States)

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

    2014-01-01

    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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  1. REINTRODUCTION OF NOBLE CRAYFISH ASTACUS ASTACUS AFTER CRAYFISH PLAGUE IN NORWAY

    Directory of Open Access Journals (Sweden)

    TAUGBØL T.

    2004-01-01

    Full Text Available The Glomma and Halden watercourses in Norway were hit by crayfish plague in 1987 and 1989. Reintroduction of the noble crayfish started in 1989 in the Glomma and in 1995 in the Halden watercourse. Norway has especially good conditions for reintroduction of the native crayfish after crayfish plague, as there is no alien plague-carrying crayfish species in the country. In the Glomma watercourse, approx. 15 000 adult crayfish and 10 000 juveniles have been stocked while in the Halden watercourse the figures are 19 000 adults and 26 500 juveniles. All stocking sites were previously regarded as very good crayfish localities. Four years after stocking, natural recruitment was recorded at all adult crayfish stocking sites in the Glomma watercourse and at most sites in the Halden watercourse. Current crayfish density is, however, much lower than pre-plague densities even at the sites where population development has been in progress for more than 10 years. Extensive post-stocking movements were recorded among adult crayfish. Some sites seemed more suitable for settling, resulting in a great variation in CPUE between the different test-fishing sites. Juveniles seem more appropriate as stocking material if the goal is to re-establish a population in a particular area, due to their stationary behaviour, which seems to remain as they grow larger.

  2. Transverse--Harris--lines in a skeletal population from the 1711 Danish plague site

    DEFF Research Database (Denmark)

    Fiscella, Gabriela N; Bennike, Pia; Lynnerup, Niels

    2008-01-01

    This study examines the occurrence and distribution of transverse lines in skeletal remains from the Copenhagen site, a plague cemetery dated 1711 AD. A relatively low frequency for evidence of line formation was observed in the individuals comprising the total sample and no transverse lines were...

  3. The galenic plague: a breakdown of the imperial pathocoenosis. Pathocoenosis and longue durée.

    Science.gov (United States)

    Gourevitch, Danielle

    2005-01-01

    Is 'pathocoenosis', a notion conceived and a word coined by Mirko Grmek (1969), useful as far as ancient history is concerned? The author is interested in Galenic pathocoenosis, that of doctor Galen and his Emperor Marcus Aurelius (IInd cent. A.D.), when a new 'pestilence' or 'plague' (smallpox?) devastated the whole empire, from Mesopotamia to the Danube at least.

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

    Centers for Disease Control (CDC) Podcasts

    2013-10-28

    Reginald Tucker reads an abridged version of the Emerging Infectious Diseases’ historical Review, Quinto Tiberio Angelerio and New Measures for Controlling Plague in 16th -Centruy Alghero, Sardinia.  Created: 10/28/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/30/2013.

  5. Lessons from the History of Quarantine, from Plague to Influenza A

    Centers for Disease Control (CDC) Podcasts

    2013-05-08

    Reginald Tucker reads an abridged version of the Emerging Infectious Diseases’ Historical Review, Lessons from the History of Quarantine, from Plague to Influenza A.  Created: 5/8/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 5/15/2013.

  6. A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

    Science.gov (United States)

    Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

    2015-03-01

    Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

  7. [Analysis on the results of etiology and serology of plague in Qinghai province from 2001 to 2010].

    Science.gov (United States)

    Yang, Yonghai; Wang, Mei; Zhao, Xiaolong; Zhao, Zhongzhi; Zhang, Aiping; Wei, Rongjie; Wei, Baiqing; Wang, Zuyun

    2014-02-01

    To analyze the results of etiology and serology of plague among human and infected animals in Qinghai province from 2001 to 2010. Thirty-seven cases of human infected with plague, 53 541 different animal samples, 5 685 sets of vector insects flea and 49 039 different animal serum samples were obtained between 2001 and 2010. A total of 7 811 samples of serum from healthy farmers and herdsmen in 14 counties in Qinghai from 2005 to 2007 were collected. Yersinia pestis (Y. pestis) were detected in visceral and secretions from human, infected animals and vector insects, respectively. Plague antigen was detected by reverse indirect hemagglutination assay (RIHA) in those samples. Indirect hemagglutination assay (IHA) was used to test plague FI antibody in serum of human and infected animals. 37 human plague cases were confirmed, 21 strains of plague Y. pestis were isolated from human cases and 14 positive were detected out. 133 of 7 811 samples of human serum were IHA positive, with the positive rate at 1.7%. A total of 146 strains of plague were isolated from infected animals and vector insects, 99 out of which were from infected animals, with a ratio of Marmota himalayan at 72.7% (72/99) and the other 47 were from vector insects, with a ratio of callopsylla solaris at 68.1% (32/47). The number of IHA and PIHA positive were 300 and 10, respectively. A total of 3 animals and 3 insects species were identified as new epidemic hosts for plague. The natural plague focus of Microtus fuscus was discovered and confirmed and coexisted with natural focus of Marmota himalayan in Chengduo county, Yushu prefecture. The epidemic situation of plague is distributed mainly in Haixi, Yushu and Hainan prefectures. From 2001 to 2010, animal infected with plague was detected in successive years and human plague was very common in Qinghai. New infected animals and vector insects species and new epidemic areas were confirmed, hence the trend of plague prevalence for humans and animals is very

  8. Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in Montana

    Science.gov (United States)

    Matchett, Marc R.; Biggins, Dean E.; Carlson, Valerie; Powell, Bradford; Rocke, Tonie E.

    2010-01-01

    Black-footed ferrets (Mustela nigripes) require extensive prairie dog colonies (Cynomys spp.) to provide habitat and prey. Epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. In addition to epizootics, we hypothesized that enzootic plague, that is, presence of disease-causing Yersinia pestis without any noticeable prairie dog die off, may also affect ferret survival. We reduced risk of plague on portions of two ferret reintroduction areas by conducting flea control for 3 years. Beginning in 2004, about half of the ferrets residing on dusted and nondusted colonies were vaccinated against plague with an experimental vaccine (F1-V fusion protein). We evaluated 6-month reencounter rates (percentage of animals observed at the end of an interval that were known alive at the beginning of the interval), an index to survival, for ferrets in four treatment groups involving all combinations of vaccination and flea control. For captive-reared ferrets (115 individuals observed across 156 time intervals), reencounter rates were higher for vaccinates (0.44) than for nonvaccinates (0.23, p = 0.044) on colonies without flea control, but vaccination had no detectable effect on colonies with flea control (vaccinates = 0.41, nonvaccinates = 0.42, p = 0.754). Flea control resulted in higher reencounter rates for nonvaccinates (p = 0.026), but not for vaccinates (p = 0.508). The enhancement of survival due to vaccination or flea control supports the hypothesis that enzootic plague reduces ferret survival, even when there was no noticeable decline in prairie dog abundance. The collective effects of vaccination and flea control compel a conclusion that fleas are required for maintenance, and probably transmission, of plague at enzootic levels. Other studies have demonstrated similar effects of flea control on several species of prairie dogs and, when combined with this study, suggest

  9. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.

    Directory of Open Access Journals (Sweden)

    Florita Flores

    Full Text Available Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata more than the upright branching species (Acropora millepora. The lowest sediment treatments that caused full colony mortality were 30 mg l(-1 TSS (25 mg cm(-2 day(-1 for M. aequituberculata and 100 mg l(-1 TSS (83 mg cm(-2 day(-1 for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue.

  10. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    Science.gov (United States)

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  11. Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

    Science.gov (United States)

    Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C

    2015-01-01

    Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.

  12. Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.

    Science.gov (United States)

    Percopo, Caroline M; Rice, Tyler A; Brenner, Todd A; Dyer, Kimberly D; Luo, Janice L; Kanakabandi, Kishore; Sturdevant, Daniel E; Porcella, Stephen F; Domachowske, Joseph B; Keicher, Jesse D; Rosenberg, Helene F

    2015-09-01

    We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

    2016-01-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

  16. [IMPACT OF CASPIAN SEA LEVEL FLUCTUATIONS ON THE EPIZOOTIC ACTIVITY OF THE CASPIAN SANDY NATURAL PLAGUE FOCUS].

    Science.gov (United States)

    Popov, N V; Udovikov, A I; Eroshenko, G A; Karavaeva, T B; Yakovlev, S A; Porshakov, A M; Zenkevich, E S; Kutyrev, V V

    2016-01-01

    There is evidence that in 1923-2014 the sharp aggravations of the epizootic situation of plague in the area of its Caspian sandy natural focus after long interepizootic periods are in time with the ups of the Caspian Sea in the extrema of 11-year solar cycles. There were cases of multiple manifestations of plague in the same areas in the epizootic cycles of 1946-1954, 1979-1996, 2001, and 2013-2014. The paper considers the possible role of amebae of the genus Acanthamoeba and nematodes, the representatives of the orders Rhabditida and Tylenchida in the microfocal pattern of plague manifestations.

  17. Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

    Science.gov (United States)

    Sorrentino, Antonella; Trotta, Silvia; Colucci, Anna Pia; Aventaggiato, Lucia; Marzullo, Andrea; Solarino, Biagio

    2018-03-19

    "Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

  18. Tumor clone dynamics in lethal prostate cancer.

    Science.gov (United States)

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. Copyright © 2014, American Association for the Advancement of Science.

  19. Human cooperation by lethal group competition.

    Science.gov (United States)

    Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W

    2013-01-01

    Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival ("looting"). Here, we find within-group cooperation to last when between-group conflict is implemented as "all-out war" (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together.

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

    Science.gov (United States)

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

    2017-10-10

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

  1. Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.

    Directory of Open Access Journals (Sweden)

    Clement W Gnanadurai

    Full Text Available Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico correlates with the presence of high level of virus neutralizing antibodies (VNA in the cerebral spinal fluid (CSF and mild immune cell accumulation in the central nervous system (CNS. By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

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

    Directory of Open Access Journals (Sweden)

    Luis F. Donaires

    2010-09-01

    nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4. Conclusion. Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2010-02-10

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

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

    Science.gov (United States)

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

    2016-06-08

    Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362-1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    KAUST Repository

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

    2014-01-01

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

  8. High throughput, multiplexed pathogen detection authenticates plague waves in medieval Venice, Italy.

    Science.gov (United States)

    Tran, Thi-Nguyen-Ny; Signoli, Michel; Fozzati, Luigi; Aboudharam, Gérard; Raoult, Didier; Drancourt, Michel

    2011-03-10

    Historical records suggest that multiple burial sites from the 14th-16th centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics. High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9%) samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7%) samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype. These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century.

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

    Science.gov (United States)

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

    2017-12-01

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

  10. Level of damages and economical threshold, decisive aspects in the integrated management of plagues.

    Directory of Open Access Journals (Sweden)

    Rafael Meneses

    2011-03-01

    Full Text Available The establishment and application of economical levels demand a procedure to find with precision the insects population in a given moment. In the integrated management of plagues is not allowed the idea that any insect which is feeding from a part of plants requires a control action, that is why it is very important to determine the real effect that this insect population causes to the cultivation. Any decrease in the crop, constitutes a real waste of time; but when the economical level is defined, it is included an additional factor which is the measure cost of the plagues control. The determination of damages of levels is very important for economists, farming experts and specialists; while for producers is very significant its implementation with the objective to count with a sustainable and beneficial agriculture.

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

    Directory of Open Access Journals (Sweden)

    Ana María Carrillo

    2005-04-01

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

  12. High Throughput, Multiplexed Pathogen Detection Authenticates Plague Waves in Medieval Venice, Italy

    Science.gov (United States)

    Tran, Thi-Nguyen-Ny; Signoli, Michel; Fozzati, Luigi; Aboudharam, Gérard; Raoult, Didier; Drancourt, Michel

    2011-01-01

    Background Historical records suggest that multiple burial sites from the 14th–16th centuries in Venice, Italy, were used during the Black Death and subsequent plague epidemics. Methodology/Principal Findings High throughput, multiplexed real-time PCR detected DNA of seven highly transmissible pathogens in 173 dental pulp specimens collected from 46 graves. Bartonella quintana DNA was identified in five (2.9%) samples, including three from the 16th century and two from the 15th century, and Yersinia pestis DNA was detected in three (1.7%) samples, including two from the 14th century and one from the 16th century. Partial glpD gene sequencing indicated that the detected Y. pestis was the Orientalis biotype. Conclusions These data document for the first time successive plague epidemics in the medieval European city where quarantine was first instituted in the 14th century. PMID:21423736

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

    Science.gov (United States)

    Fears, J Rufus

    2004-03-01

    The Roman Empire of the second century was a superpower that, in relative terms, dominated its world as much as the United States does today. In 166 AD, a plague broke out od pandemic proportions. The pandemic ravaged the entire extent of the Roman Empire, from its eastern frontiers in Iraq to its western frontiers on the Rhine River and Gaul, modern France, and western Germany. The disease is identified most often as smallpox, but it may have been anthrax. The study of bacterial DNA may enable identification of this plague that ravaged the Roman Empire at recurrent intervals for more than 100 years and that had a significant role in the decline and fall of this great superpower.

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

    Science.gov (United States)

    Ell, S R

    1989-01-01

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

  15. Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes.

    Science.gov (United States)

    Filges, Isabel; Friedman, Jan M

    2015-10-01

    Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis. © 2014 John Wiley & Sons, Ltd.

  16. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

    Science.gov (United States)

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

    2014-09-09

    Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

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

    OpenAIRE

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

    2009-01-01

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

  18. Identification of Risk Factors Associated with Transmission of Plague Disease in Eastern Zambia.

    Science.gov (United States)

    Nyirenda, Stanley S; Hang'ombe, Bernard M; Machang'u, Robert; Mwanza, Jackson; Kilonzo, Bukheti S

    2017-09-01

    Plague is a fatal, primarily rodent-flea-borne zoonotic disease caused by Yersinia pestis . The identification of risk factors of plague was investigated through questionnaire interview and conducting focus group discussion (FGD) in Sinda and Nyimba districts of eastern Zambia. A total of 104 questionnaires were administered to individual respondents and 20 groups consisting of 181 discussants, which comprised FGD team in this study. The study revealed that trapping, transportation, and preparation of rodents for food exposed the community to rodent and their fleas suggesting that plague may have occurred primarily by either flea bites or contact with infected wild rodents. The study also revealed that most people in communities consumed rodents as part of their regular diet; therefore, contact with small wild mammals was a common practice. The mode of transportation of freshly trapped rodents, in particular, carcasses risked human to flea bites. Questionnaire respondents (75%) and FGD discussants (55%) indicated that trappers preferred to carry rodent carcasses in small bags, whereas 55.8% and 20% respectively, reported hunters carrying carcasses in their pockets. Carrying of carcass skewers on trappers' shoulders was reported by 38.4% and 20% of individual respondents and FGD, respectively. All these activities were exposing humans to rodents and their fleas, the natural reservoirs and vectors of plague, respectively. This study also showed that there is a statistically significant (χ 2 = 4.6878, P < 0.05), between digging of rodents from their burrows and the presence of fleas on the hunter's bodies or clothes, which exposes humans to potentially flea bites in an enzootic cycle.

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

    Science.gov (United States)

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

    2006-01-01

    Commensal and field rodents and wild small carnivores were live-trapped in five villages of Karatu district and one settlement in the Ngorongoro Conservation Area in Ngorongoro district in Tanzania. Blood samples were taken and serologically tested for plague, using the Blocking ELISA technique. Some domestic dogs and cats in the Karatu villages were aseptically bled and similarly tested for plague. Fleas were collected from the examined animals and from randomly selected residential houses. A total of 241 rodents, 1 Crocidura spp, 43 dogs, 12 cats and 4 slender mongooses were involved in the survey. Of the rodents, 14.5% were infested with fleas, which comprised of Xenopsylla brasiliensis (45.8%) and Dinopsyllus lypusus (54.2%), with an overall population density of 0.2 fleas/animal. Thirty one (72.1%) of the dogs were infested with fleas, all of which were Ctenocephalides spp. Thirty five (63.3%) houses were infested with fleas whose population was composed of Ctenocephalides spp, Pulex irritans, Tunga penetrans and Echinophaga gallinacea. Infected rodents were found in all the villages while the infected dog was found at Rhotia-Kati. Nineteen (11%) of the rodents and one (2%) dog harboured specific plague antibodies. It was broadly concluded that sylvatic plague was endemic in Karatu district and Ngorongoro Conservation Area and that outbreaks of the disease can occur in the area any time if and when relevant conditions become favourable. Prompt application of appropriate preventive and control measures and survey for substantiating the status in the Lake Manyara National Park, which is adjacent to some of the infected villages, are recommended.

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

    Science.gov (United States)

    Fierros-Hernández, Arturo; Ayala-Zúñiga, Alejandro

    2018-01-01

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

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

    Science.gov (United States)

    2012-09-01

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

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

    OpenAIRE

    Mateusz Marecki

    2012-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

  4. A new type of lethal short-limbed dwarfism

    International Nuclear Information System (INIS)

    Nairn, E.R.; Chapman, S.

    1989-01-01

    Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature. (orig.)

  5. Back to the future: revisiting HIV-1 lethal mutagenesis

    Science.gov (United States)

    Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

    2012-01-01

    The concept of eliminating HIV-1 infectivity by elevating the viral mutation rate was first proposed over a decade ago, even though the general concept had been conceived earlier for RNA viruses. Lethal mutagenesis was originally viewed as a novel chemotherapeutic approach for treating HIV-1 infection in which use of a viral mutagen would over multiple rounds of replication lead to the lethal accumulation of mutations, rendering the virus population non infectious – known as the slow mutation accumulation model. There have been limitations in obtaining good efficacy data with drug leads, leaving some doubt into clinical translation. More recent studies of the APOBEC3 proteins as well as new progress in the use of nucleoside analogs for inducing lethal mutagenesis have helped to refocus attention on rapid induction of HIV-1 lethal mutagenesis in a single or limited number of replication cycles leading to a rapid mutation accumulation model. PMID:23195922

  6. New type of lethal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Nairn, E.R.; Chapman, S.

    1989-05-01

    Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature.

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

    Directory of Open Access Journals (Sweden)

    Fanny Gascuel

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

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

    Science.gov (United States)

    Wang, Xin; Wei, Xiaoyu; Song, Zhizhong; Wang, Mingliu; Xi, Jinxiao; Liang, Junrong; Liang, Yun; Duan, Ran; Tian, Kecheng; Zhao, Yong; Tang, Guangpeng; You, Lv; Yang, Guirong; Liu, Xuebin; Chen, Yuhuang; Zeng, Jun; Wu, Shengrong; Luo, Shoujun; Qin, Gang; Hao, Huijing; Jing, Huaiqi

    2017-03-01

    Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma. We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years' surveillance. The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

  9. Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus

    Science.gov (United States)

    Brouat, Carine; Rahelinirina, Soanandrasana; Loiseau, Anne; Rahalison, Lila; Rajerison, Minoariso; Laffly, Dominique; Handschumacher, Pascal; Duplantier, Jean-Marc

    2013-01-01

    Background Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. Methodology/Principal Findings We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150–200 km2 within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. Conclusions/Significance Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations. PMID:23755317

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Soanandrasana Rahelinirina

    2017-11-01

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

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

    Science.gov (United States)

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

    1991-05-01

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

  14. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague.

    Science.gov (United States)

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

    2015-12-01

    Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. A rapid field test for sylvatic plague exposure in wild animals

    Science.gov (United States)

    Abbott, Rachel C.; Hudak, Robert; Mondesire, Roy; Baeten, Laurie A.; Russell, Robin E.; Rocke, Tonie E.

    2014-01-01

    Plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. The most common surveillance method for sylvatic plague is detection of antibodies to Yersinia pestis F1 capsular antigen in sentinel animals, such as coyotes (Canis latrans). Current serologic tests for Y. pestis, hemagglutination (HA) test and enzyme-linked immunosorbent assay (ELISA), are expensive and labor intensive. To address this need, we developed a complete lateral flow device for the detection of specific antibodies to Y. pestis F1 and V antigens. Our test detected anti-F1 and anti-V antibodies in serum and Nobuto filter paper samples from coyotes, and in serum samples from prairie dogs (Cynomys ludovicianus), lynx (Lynx canadensis), and black-footed ferrets (Mustela nigripes). Comparison of cassette results for anti-F1 and anti-V antibodies with results of ELISA or HA tests showed correlations ranging from 0.68 to 0.98. This device provides an affordable, user-friendly tool that may be useful in plague surveillance programs and as a research tool.

  16. Unreliability and the Animal Narrator in Richard Adams’s The Plague Dogs

    Directory of Open Access Journals (Sweden)

    Anja Höing

    2017-03-01

    Full Text Available Richard Adams’s talking animal story The Plague Dogs (1978, with its deeply genre-atypical mode of narration, offers a multiplicity of avenues to explore the literary animal as animal. The story draws much of its power from the psychological complexity and related unreliability of both canine narrators, two research lab escapees gone feral. Both the terrier Snitter and the black mongrel Rowf are mentally ill and experience a highly subjective, part-fantastic world. In episodes of zero focalization, a sarcastic voice comments on the plot from the off, aggressively attacking a thoroughly anthropocentric superstructure the protagonists themselves are oblivious of, and presenting all that is normally constructed as “rational” in the implied reader’s world as a carnivalesque farce. Combining these equally unreliable narratives, The Plague Dogs creates a unique mixture of what Phelan (2007 calls “estranging” and “bonding” unreliability and brings to light the devastating consequences of anthropocentrism. The Plague Dogs not only defamiliarizes a genre usually committed to conventional means of storytelling, but the dominant Western conception of the status of animals in the world, showing that once we start to read the animal as animal, this sets into motion an avalanche of other concepts in need of re-reading, among them the very ones making up the fundamental pillars of Western societies’ anthropocentric self-conception.

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

    Science.gov (United States)

    Clemens, E.; Brandt, M. E.

    2015-12-01

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

  18. Factors influencing uptake of sylvatic plague vaccine baits by prairie dogs

    Science.gov (United States)

    Abbott, Rachel C.; Russell, Robin E.; Richgels, Katherine; Tripp, Daniel W.; Matchett, Marc R.; Biggins, Dean E.; Rocke, Tonie E.

    2017-01-01

    Sylvatic plague vaccine (SPV) is a virally vectored bait-delivered vaccine expressing Yersinia pestis antigens that can protect prairie dogs (Cynomys spp.) from plague and has potential utility as a management tool. In a large-scale 3-year field trial, SPV-laden baits containing the biomarker rhodamine B (used to determine bait consumption) were distributed annually at a rate of approximately 100–125 baits/hectare along transects at 58 plots encompassing the geographic ranges of four species of prairie dogs. We assessed site- and individual-level factors related to bait uptake in prairie dogs to determine which were associated with bait uptake rates. Overall bait uptake for 7820 prairie dogs sampled was 70% (95% C.I. 69.9–72.0). Factors influencing bait uptake rates by prairie dogs varied by species, however, in general, heavier animals had greater bait uptake rates. Vegetation quality and day of baiting influenced this relationship for black-tailed, Gunnison’s, and Utah prairie dogs. For these species, baiting later in the season, when normalized difference vegetation indices (a measure of green vegetation density) are lower, improves bait uptake by smaller animals. Consideration of these factors can aid in the development of species-specific SPV baiting strategies that maximize bait uptake and subsequent immunization of prairie dogs against plague.

  19. Controlling Ebola: what we can learn from China's 1911 battle against the pneumonic plague in Manchuria

    Directory of Open Access Journals (Sweden)

    He Liu

    2015-04-01

    Full Text Available The pneumonic plague, which spread across Northeast China during the winter of 1910 and spring of 1911, caused numerous deaths and brought about severe social turmoil. After compulsory quarantine and other epidemic prevention measures were enforced by Dr Wu Lien-teh, the epidemic was brought to an end within 4 months. This article reviews the ways in which the plague was dealt with from a historical perspective, based on factors such as clinical manifestations, duration of illness, case fatality rate, degree of transmissibility, poverty, inadequate healthcare infrastructure, and the region's recent strife-filled history. Similarities were sought between the pneumonic plague in Northeast China in the twentieth century and the Ebola virus outbreak that is currently ravaging Africa, and an effort made to summarize the ways in which specific measures were applied successfully to fight the earlier epidemic. Our efforts highlight valuable experiences that are of potential benefit in helping to fight the current rampant Ebola epidemic in West Africa.

  20. Perinatal-lethal Gaucher disease presenting as hydrops fetalis.

    Science.gov (United States)

    BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

    2015-01-01

    Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis.

  1. Conflict Without Casualties: Non-Lethal Weapons in Irregular Warfare

    Science.gov (United States)

    2007-09-01

    the body,” and the Geneva Protocol of 1925, bans the use of chemical and biological weapons .11 On 8 April 1975, President Ford issued Executive...E Funding – PE 63851M) (accessed 15 December 2006). The American Journal of Bioethics . “Medical Ethics and Non-Lethal Weapons .” Bioethics.net...CASUALTIES: NON-LETHAL WEAPONS IN IRREGULAR WARFARE by Richard L. Scott September 2007 Thesis Advisor: Robert McNab Second Reader

  2. Non-Lethal Weapons: Opportunities for R&D

    Science.gov (United States)

    2004-12-01

    during the Vietnam War. US; emulsifying agents are used in food processing, drilling fluids, cosmetics , pharmaceuticals, heavy- duty cleaners, textile...conducted in a professional manner, with no threat to public safety or the environment. 11 References [1] Fenton , G., (2001). NLW Technology Taxonomy...W.A., Mason, R.L., Collins, K.R., (2000). Non-Lethal Applicants of Slippery Substances. NDIA Non-Lethal Defense IV. [24] Fenton , G., (2000). Overview

  3. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

    Science.gov (United States)

    Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-12-01

    One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

  4. Sonographic features of lethal multiple pterygium syndrome at 14 weeks.

    Science.gov (United States)

    Chen, Min; Chan, Gavin Shueng Wai; Lee, Chin Peng; Tang, Mary Hoi Yin

    2005-06-01

    Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports suggest that the diagnosis may be based on prenatal sonographic demonstration of severe limb flexion, absence of fetal motion, and a large cystic hygroma in the second and third trimesters. We present the sonographic features and postmortem features of a fetus with lethal multiple pterygium syndrome at 13 weeks of gestation, which shows that the condition can possibly be diagnosed in the first trimester of pregnancy.

  5. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Lilly

    2018-01-01

    Full Text Available Polymicrobial intra-abdominal infections (IAIs are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis. Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge. Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO] survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  6. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

    Science.gov (United States)

    Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

    2018-01-01

    ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  7. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after...... with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0...... but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria....

  8. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    Energy Technology Data Exchange (ETDEWEB)

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C. (UMM)

    2016-07-05

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

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

    Science.gov (United States)

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

    2017-05-16

    Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that Yersinia pestis LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys 273 and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys 273 Ala in lcrV Moreover, the lcrV C273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys 273 Ala substitution. Furthermore, macrophages infected by the lcrV C273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB , which encodes glutathione synthetase of Y. pestis , resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis Δ gshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione. IMPORTANCE Yersinia pestis , the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of Y. pestis in mouse and rat

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

    Science.gov (United States)

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

    1997-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  13. Development of non-lethal methods for investigation of actinide uptake by wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, M.; Child, D.; Davis, E.; Harrison, J.; Hotchkis, M.; Payne, T.; Thiruvoth, S. [Australian Nuclear Science and Technology Org. (Australia); Wood, M. [University of Salford (United Kingdom)

    2014-07-01

    There is growing interest in the use of non-lethal methods in radioecology and an International Union of Radioecology Task Group has been established to facilitate international cooperation in this field (http://iur-uir.org/en/task-groups/id-19-non-lethal-methods-in-radioecology). In this paper, we evaluate the use of lethally-, and non-lethally obtained samples (various body tissues, excreta and blood withdrawals as well as parasites and found bones) as indicators of contamination. Samples of mammals and reptiles were collected from the semi-arid former weapons test site at Maralinga, Australia and analysed for thorium, plutonium, and uranium isotopes by accelerator mass spectrometry and alpha-spectrometry. Most samples were of low mass and presented analytical challenges as a result. The plutonium concentrations in blood withdrawn from the marginal ear veins of Oryctolagus cuniculus (European rabbit) were successfully analysed using small samples (0.2 -7.9 ml, below the ∼10 ml threshold for safe extraction of blood from these rabbits). The results demonstrate that small-volume blood samples can serve as indicators of the presence of plutonium absorbed within other tissues (e.g., muscle, bone). However, the magnitude of the blood plutonium masses were poorly correlated with those in muscle and bone due to the presence of a small number of outliers (without the outliers, correlations improved to r = +0.66 and r = +0.51 for muscle and bone respectively). The activity concentrations in parasitic ticks were relatively high compared with those of their hosts Pseudomys hermannsburgensis (sandy inland mouse) and Ctenophorus cristatus (crested dragon lizard). Successful measurement of tick samples indicates a potential for use of parasites as general indicators of contamination within host organisms. The concentrations of actinides in found bones of Macropus rufus (red kangaroo) and O. cuniculus demonstrated potential for their use as indicators of the areal extent of

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

    National Research Council Canada - National Science Library

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

    2008-01-01

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

  15. Empirical complexities in the genetic foundations of lethal mutagenesis.

    Science.gov (United States)

    Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

    2013-10-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

  16. A multivariate model of stakeholder preference for lethal cat management.

    Science.gov (United States)

    Wald, Dara M; Jacobson, Susan K

    2014-01-01

    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n=1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI=0.94, RMSEA=0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (pstakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.

  17. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    International Nuclear Information System (INIS)

    Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

    2014-01-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  18. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

    Science.gov (United States)

    Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

  19. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  20. Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

    International Nuclear Information System (INIS)

    Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

    2007-01-01

    We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3 + T cells are required for protection

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

    Science.gov (United States)

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

    2018-02-06

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

  2. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    1983-03-01

    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

  3. Analysis of time of death of prenatally lethal Steeloid mutations

    International Nuclear Information System (INIS)

    Rinchik, E.M.; Cummings, C.C.; Bangham, J.W.; Hunsicker, P.R.; Phipps, E.L.; Stelzner, K.F.

    1987-01-01

    Deletion mutations have been extremely useful in initiating the functional and molecular dissections of regions of the mouse genome. For the d-se and c regions, for example, it was observed that radiation mutations carrying lethal factors separable, by complementation analysis, from the primary d, se, or c mutation itself, could often be associated at both the genetic and molecular levels with multilocus chromosomal deletions. Since many of the Oak Ridge Sld mutations arose in radiation mutagenesis experiments, a substantial number may carry chromosomal deletions that involve the Sl locus in chromosome 10. Because of the great value of deletion mutations for the genetic and molecular analysis of chromosomal regions and complex genetic loci, they have initiated a series of experiments designed to test whether radiation-induced Sld mutations carry other lethal factors, in addition to the lethality caused by severe alleles of the Sl locus itself, as one prescreen for identifying Sld's that are caused by deletions

  4. The Effects of Anthrax Lethal Toxin on Host Barrier Function

    Directory of Open Access Journals (Sweden)

    David M. Frucht

    2011-06-01

    Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

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

    Directory of Open Access Journals (Sweden)

    Amy J Vogler

    2017-09-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

    Eads, David A; Hoogland, John L

    2017-08-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    Gyuranecz, Miklós

    2015-01-01

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

  10. Early events of lethal action by tobramycin in Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Raulston, J.E.

    1988-01-01

    The immediate activities of the aminoglycoside antibiotic, tobramycin, were investigated in Pseudomonas aeruginosa PAO1. The influence of carbon growth substate and the antibiotic exposure environment in the magnitude of activity were examined. Lethality by 8 μg/ml tobramycin occurred rapidly (1 to 3 minutes). The release of specific cellular components into the supernatant was associated with lethality. This material was initially detected as an increase in UV-absorbance. Magnesium in the reaction mixture provided protection against lethality and leakage, but did not reverse lethal damage after a 3 minute tobramycin treatment. Also, uptake of 3 H-tobramycin was reduced in the presence of magnesium. Cells grown with glucose as a carbon source were more susceptible than organic acid grown cells as was the rapidity and amount of cell damage. Analyses of the leakage material revealed a 2-fold increase of protein in the supernatant after a 1-3 minute treatment which paralleled lethality. A prominent 29 kDa protein was observed by SDS-PAGE in the released material, which has been identified as the periplasmic enzyme, β-lactamase. The immediate activities of tobramycin did not involve (i) release of overall cell protein, (ii) massive loss of total pool amino acids, (iii) cell lysis, (iv) inhibition of proline uptake, (v) release of lipopolysaccharide, or (vi) leakage of ATP. Electron microscopy showed no apparent damage after a 3 minute exposure. 40% inhibition of protein synthesis had occurred by 3 minutes of exposure, while release of UV-absorbing material and lethality were detectable after only 1 minute. Resistant cystic fibrosis isolates of P. aeruginosa did not leak under the same experimental conditions, but one of two susceptible strains examined did show increased UV-absorbance following treatment

  11. Impact of acute alcohol consumption on lethality of suicide methods.

    Science.gov (United States)

    Park, C Hyung Keun; Yoo, Seong Ho; Lee, Jaewon; Cho, Sung Joon; Shin, Min-Sup; Kim, Eun Young; Kim, Se Hyun; Ham, Keunsoo; Ahn, Yong Min

    2017-05-01

    The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Challenges to reestablishment of free-ranging populations of black-footed ferrets

    Science.gov (United States)

    Biggins, D.E.; Godbey, J.L.

    2003-01-01

    The black-footed ferret (Mustela nigripes) of North America is critically endangered due in part to its extreme specialization on formerly stable and abundant prairie dogs (Cynomys). Its close relative, the Siberian polecat (M. eversmannii) seems to have been subjected to a varying environment that was not conducive to specialization. One source of environmental variation in Asian steppes was plague (caused by Yersina pestis), which was absent from North America. Introduction of plague to North America presents serious challenges to ferret recovery. Partial solutions to other biological and political problems have been found, resulting in improved production in captivity, increased survival post-release, and thriving populations in plague-free South Dakota.

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

    Directory of Open Access Journals (Sweden)

    Karel Černý

    2012-01-01

    Full Text Available The paper deals with the problem of early modern scientific citations. It attempts to establish a measure of scientific popularity in a specific area of the academic medicine in a way which resembles a modern evaluation of scientific activity (citation index. For this purpose an analysis of a series of plague treatises written between 1480 and 1725 in Europe was conducted. Citations for various historical medical authorities (Hippocrates, Galen, etc. are given in Tables which reflect a long time development of popularity. The authorities from various groups (Ancient, Medieval, Arabic, Early Modern are linked together, and “generic authorities” are explained and discussed.

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

    Science.gov (United States)

    Kutyrev, V V; Smirnova, N I

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stephanie O. Crofton

    2005-01-01

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

  16. Lethals induced by γ-radiation in drosophila somatic cells

    International Nuclear Information System (INIS)

    Ivanov, A.I.

    1989-01-01

    Exposure of 3-hour drosophila male embryos to γ-radiation during the topographic segregation of the germ anlage nuclei caused recessive sex-linked lethals in somatic cells only. The selectivity of the screening was determined by the ratio of mutation frequencies induced in embryos and adult males. Analysis of lethal mutations shows that a minimal rate of the divergence between germinal and somatic patterns of the cell development is observed in the embryogenesis, the 3d instar larva and prepupa, and maximal in the 1st and 2nd larva and pupa

  17. Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

    Science.gov (United States)

    Pauly, Matthew D; Lauring, Adam S

    2015-04-01

    Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

  18. "Rickettsia amblyommii" induces cross protection against lethal Rocky Mountain spotted fever in a guinea pig model.

    Science.gov (United States)

    Blanton, Lucas S; Mendell, Nicole L; Walker, David H; Bouyer, Donald H

    2014-08-01

    Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia rickettsii for which there is no available vaccine. We hypothesize that exposure to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii" protects against R. rickettsii challenge. To test this hypothesis, guinea pigs were inoculated with "R. amblyommii." After inoculation, the animals showed no signs of illness. When later challenged with lethal doses of R. rickettsii, those previously exposed to "R. amblyommii" remained well, whereas unimmunized controls developed severe illness and died. We conclude that "R. amblyommii" induces an immune response that protects from illness and death in the guinea pig model of RMSF. These results provide a basis for exploring the use of low-virulence rickettsiae as a platform to develop live attenuated vaccine candidates to prevent severe rickettsioses.

  19. Enhancement of Hsp70 synthesis protects common carp, Cyprinus carpio L., against lethal ammonia toxicity.

    Science.gov (United States)

    Sung, Y Y; Roberts, R J; Bossier, P

    2012-08-01

    Exposure to TEX-OE®, a patented extract of the prickly pear cactus (Opuntia ficus indica) containing chaperone-stimulating factor, was shown to protect common carp, Cyprinus carpio L., fingerlings against acute ammonia stress. Survival was enhanced twofold from 50% to 95% after exposure to 5.92 mg L(-1) NH(3) , a level determined in the ammonia challenge bioassay as the 1-h LD50 concentration for this species. Survival of TEX-OE®-pre-exposed fish was enhanced by 20% over non-exposed controls during lethal ammonia challenge (14.21 mg L(-1)  NH(3) ). Increase in the levels of gill and muscle Hsp70 was evident in TEX-OE®-pre-exposed fish but not in the unexposed controls, indicating that application of TEX-OE® accelerated carp endogenous Hsp70 synthesis during ammonia perturbation. Protection against ammonia was correlated with Hsp70 accretion. © 2012 Blackwell Publishing Ltd.

  20. Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

    Directory of Open Access Journals (Sweden)

    Liling Yang

    2017-10-01

    Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

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

    Science.gov (United States)

    Mertens, T

    1999-01-01

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

  2. Functional diversity of non-lethal effects, chemical camouflage, and variation in fish avoidance in colonizing beetles.

    Science.gov (United States)

    Resetarits, William J; Pintar, Matthew R

    2016-12-01

    Predators play an extremely important role in natural communities. In freshwater systems, fish can dominate sorting both at the colonization and post-colonization stage. Specifically, for many colonizing species, fish can have non-lethal, direct effects that exceed the lethal direct effects of predation. Functionally diverse fish species with a range of predatory capabilities have previously been observed to elicit functionally equivalent responses on oviposition in tree frogs. We tested this hypothesis of functional equivalence of non-lethal effects for four predatory fish species, using naturally colonizing populations of aquatic beetles. Among taxa other than mosquitoes, and with the exception of the chemically camouflaged pirate perch, Aphredoderus sayanus, we provide the first evidence of variation in colonization or oviposition responses to different fish species. Focusing on total abundance, Fundulus chrysotus, a gape-limited, surface-feeding fish, elicited unique responses among colonizing Hydrophilidae, with the exception of the smallest and most abundant taxa, Paracymus, while Dytiscidae responded similarly to all avoided fish. Neither family responded to A. sayanus. Analysis of species richness and multivariate characterization of the beetle assemblages for the four fish species and controls revealed additional variation among the three avoided species and confirmed that chemical camouflage in A. sayanus results in assemblages essentially identical to fishless controls. The origin of this variation in beetle responses to different fish is unknown, but may involve variation in cue sensitivity, different behavioral algorithms, or differential responses to species-specific fish cues. The identity of fish species occupying aquatic habitats is crucial to understanding community structure, as varying strengths of lethal and non-lethal effects, as well as their interaction, create complex landscapes of predator effects and challenge the notion of functional

  3. Black plague

    Energy Technology Data Exchange (ETDEWEB)

    MacIsaac, M.

    1995-09-01

    The Canadian government has eliminated the subsidy that Cape Breton Development Corporation (Devco) has received for the past 27 years (averaging $59.5 million annually for the last decade). Other problems facing Devco include privatization of two of Devco`s major customers, demand for lower coal prices, absenteeism, union difficulties, and problems with the Phalen mine. Pittsburgh`s John T. Boyd Co. was hired in May to assess Devco`s operations and its ability to compete with other coal mining companies. In July, Joe Shannon was appointed as the new president of Devco and given the mandate of making Devco commercially viable, with privatization in the longer term. Shannon will attempt to determine whether the mine`s problems with production are due to bad management or to technical problems and geology. 1 fig.

  4. Plague Factsheet

    Science.gov (United States)

    ... Many other rodent species, for instance, prairie dogs, wood rats, chipmunks, and other ground squirrels and their ... or by citizens reporting rodents found sick or dead to local health departments. Use of appropriate and ...

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

    Science.gov (United States)

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

    2016-01-01

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

  6. [Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

    Science.gov (United States)

    Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

    2014-01-01

    Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Emergence, spread, persistence and fade-out of sylvatic plague in Kazakhstan

    Science.gov (United States)

    Heier, Lise; Storvik, Geir O.; Davis, Stephen A.; Viljugrein, Hildegunn; Ageyev, Vladimir S.; Klassovskaya, Evgeniya; Stenseth, Nils Chr.

    2011-01-01

    Predicting the dynamics of zoonoses in wildlife is important not only for prevention of transmission to humans, but also for improving the general understanding of epidemiological processes. A large dataset on sylvatic plague in the Pre-Balkhash area of Kazakhstan (collected for surveillance purposes) provides a rare opportunity for detailed statistical modelling of an infectious disease. Previous work using these data has revealed a host abundance threshold for epizootics, and climatic influences on plague prevalence. Here, we present a model describing the local space–time dynamics of the disease at a spatial scale of 20 × 20 km2 and a biannual temporal scale, distinguishing between invasion and persistence events. We used a Bayesian imputation method to account for uncertainties resulting from poor data in explanatory variables and response variables. Spatial autocorrelation in the data was accounted for in imputations and analyses through random effects. The results show (i) a clear effect of spatial transmission, (ii) a high probability of persistence compared with invasion, and (iii) a stronger influence of rodent abundance on invasion than on persistence. In particular, there was a substantial probability of persistence also at low host abundance. PMID:21345866

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anthony Mitchell

    2017-05-01

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

  11. Practical disinfection chemicals for fishing and crayfishing gear against crayfish plague transfer

    Directory of Open Access Journals (Sweden)

    Jussila J.

    2014-01-01

    Full Text Available We tested four commercial disinfectants against crayfish plague (Aphanomyces astaci spores in both aquatic solutions and with material mimicking fishing and crayfishing gear, e.g. traps, ropes, mesh, etc. The tested disinfectants were Proxitane®5:14, Proxitane®12:20, Wofasteril®E400, Virkon®S and hydrogen peroxide. The effects of the chemicals were initially tested in liquid zoospore cultures and the effective concentrations were then further tested using clean and dirty model materials (PP sheet, nylon rope, cotton fabric contaminated with A. astaci spore solutions. The disinfectants effective against infective crayfish plague spores with both clean and dirty model materials were Proxinate®5:14 (effective concentration was 30 mg·L-1 of PAA and Virkon®S (3 g·L-1, while Proxinate®12:20 (10 mg·L-1 of PAA and Wofasteril®E400 (30 mg·L-1 of PAA worked only with clean model materials. Hydrogen peroxide was not effective in the tested concentrations and conditions. Based on the results, the disinfectants most suitable for the fishing and crayfishing gear disinfection would be Proxitane®5:14 and Virkon®S, with the condition that all the gear should be thoroughly cleaned of organic matter to ensure inactivation of A. astaci spores.

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

    Directory of Open Access Journals (Sweden)

    Ricardo Augusto dos Santos

    2006-03-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  14. Computational Psychiatry and the Challenge of Schizophrenia

    Science.gov (United States)

    Murray, John D.; Chekroud, Adam M.; Corlett, Philip R.; Yang, Genevieve; Wang, Xiao-Jing; Anticevic, Alan

    2017-01-01

    Abstract Schizophrenia research is plagued by enormous challenges in integrating and analyzing large datasets and difficulties developing formal theories related to the etiology, pathophysiology, and treatment of this disorder. Computational psychiatry provides a path to enhance analyses of these large and complex datasets and to promote the development and refinement of formal models for features of this disorder. This presentation introduces the reader to the notion of computational psychiatry and describes discovery-oriented and theory-driven applications to schizophrenia involving machine learning, reinforcement learning theory, and biophysically-informed neural circuit models. PMID:28338845

  15. Perforated appendicitis presenting as a thigh abscess: A lethal ...

    African Journals Online (AJOL)

    Typical cases of acute appendicitis have excellent treatment outcomes, if managed appropriately.1 We discuss an unusual case of perforated retrocaecal appendicitis that presented as a right thigh abscess without prominent abdominal symptoms, which highlights the lethal nature of advanced appendicitis even when ...

  16. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  17. The "Lethal Chamber": Further Evidence of the Euthanasia Option.

    Science.gov (United States)

    Elks, Martin A.

    1993-01-01

    Historical discussions of the euthanasia or "lethal chamber" option in relation to people with mental retardation are presented. The paper concludes that eugenic beliefs in the primacy of heredity over environment and the positive role of natural selection may have condoned the poor conditions characteristic of large, segregated institutions and…

  18. Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

    NARCIS (Netherlands)

    Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.

    2006-01-01

    Papaya lethal yellowing virus (PLYV) é um dos três vírus descritos infectando mamoeiros (Carica papaya L.) no Brasil. Vasconcellea cauliflora (Jacq.) A. DC., antes denominada de Carica cauliflora (Jacq.), é uma reconhecida fonte de resistência natural ao Papaya ringspot virus (PRSV), causador da

  19. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  20. Fighting Lethal Yellowing Disease for Coconut Farmers (CIFSRF ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Copra is the dried kernel of the coconut, which is used to extract coconut oil. Coconut is the main income source for the coastal region's poor farmers. Over the past 10 years, Côte d'Ivoire lethal yellowing disease has destroyed more than 350 hectares of coconut and caused losses of 12,000 tons of copra per year.

  1. Why the United States Must Adopt Lethal Autonomous Weapon Systems

    Science.gov (United States)

    2017-05-25

    intelligence , Lethal Autonomous Weapon Systems, energy production, energy storage, three-dimensional printing , bandwidth improvements, computer...views on the morality of artificial intelligence (AI) and robotics technology. Eastern culture sees artificial intelligence as an economic savior...capable of improving their society. In contrast, Western culture regards artificial intelligence with paranoia, anxiety, and skepticism. As Eastern

  2. A hepatic protein, fetuin-A, occupies a protective role in lethal systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Wei Li

    2011-02-01

    Full Text Available A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI, and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.LSI was induced by endotoxemia or cecal ligation and puncture (CLP in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin or endogenous (IFN-γ stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24-48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50-70% of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20-100 mg/kg dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro.These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release.

  3. Influence of temperature and pressure on the lethality of ultrasound

    International Nuclear Information System (INIS)

    Raso, J.; Pagan, R.; Condon, S.; Sala, F.J.

    1998-01-01

    A specially designed resistometer was constructed, and the lethal effect on Yersinia enterocolitica of ultrasonic waves (UW) at different static pressures (manosonication [MS]) and of combined heat-UW under pressure treatments (manothermosonication [MTS]) was investigated. During MS treatments at 30 degrees C and 200 kPa, the increase in the amplitude of UW of 20 kHz from 21 to 150 micrometers exponentially decreased decimal reduction time values (D(MS)) from 4 to 0.37 min. When pressure was increased from 0 to 600 kPa at a constant amplitude (150 micrometers) and temperature (30 degrees C), D(MS) values decreased from 1.52 to 0.20 min. The magnitude of this decrease in D(MS) declined progressively as pressure was increased. The influence of pressure on D(MS) values was greater with increased amplitude of UW. Pressure alone of as much as 600 kPa did not influence the heat resistance of Y. enterocolitica (D60 = 0.094; zeta = 5.65). At temperatures of as much as 58 degrees C, the lethality of UW under pressure was greater than that of heat treatment alone at the same temperature. At higher temperatures, this difference disappeared. Heat and UW under pressure seemed to act independently. The lethality of MTS treatments appeared to result from the added effects of UW under pressure and the lethal effect of heat. The individual contributions of heat and of UW under pressure to the total lethal effect of MTS depended on temperature. The inactivating effect of UW was not due to titanium particles eroded from the sonication horn. The addition to the MS media of cysteamine did not increase the resistance of Y. enterocolitica to MS treatment. MS treatment caused cell disruption

  4. Annotating novel genes by integrating synthetic lethals and genomic information

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou

    2008-01-01

    Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

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

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2017-03-01

    Full Text Available Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma.We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years' surveillance.The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

  6. Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

    Science.gov (United States)

    Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

    2018-01-16

    Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non- albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans / S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis / S. aureus -mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis -induced protection. C. dubliniensis / S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1 hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1 + cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans / S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

  7. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

    Science.gov (United States)

    Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

    2017-01-01

    Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

  8. Noninvasive risk stratification of lethal ventricular arrhythmias and sudden cardiac death after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Kenji Yodogawa, MD

    2014-08-01

    Full Text Available Prediction of lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important and challenging problems after myocardial infarction (MI. Identification of MI patients who are prone to ventricular tachyarrhythmias allows for an indication of implantable cardioverter-defibrillator placement. To date, noninvasive techniques such as microvolt T-wave alternans (MTWA, signal-averaged electrocardiography (SAECG, heart rate variability (HRV, and heart rate turbulence (HRT have been developed for this purpose. MTWA is an indicator of repolarization abnormality and is currently the most promising risk-stratification tool for predicting malignant ventricular arrhythmias. Similarly, late potentials detected by SAECG are indices of depolarization abnormality and are useful in risk stratification. However, the role of SAECG is limited because of its low predictive accuracy. Abnormal HRV and HRT patterns reflect autonomic disturbances, which may increase the risk of lethal ventricular arrhythmias, but the existing evidence is insufficient. Further studies of noninvasive assessment may provide a new insight into risk stratification in post-MI patients.

  9. Reliability of non-lethal assessment methods of body composition and energetic status exemplified by applications to eel (Anguilla anguilla) and carp (Cyprinus carpio)

    DEFF Research Database (Denmark)

    Klefoth, Thomas; Skov, Christian; Aarestrup, Kim

    2013-01-01

    tNon-lethal assessments of proximate body composition of fish can help unravelling the physiologicaland condition-dependent mechanisms of individual responses to ecological challenges. Common non-lethal methods designed to index nutrient composition in fish include the relative condition factor (Kn......),bioelectric impedance-based assessments of body composition (BIA), and microwave-based “fat” meters(FM). Previous studies have revealed mixed findings as to the reliability of each of these. We compared theperformance of Kn, BIA and FM at different temperatures to predict energetic status of the whole bodiesof live eel...... approach isthe most suitable method to non-lethally estimate energetic status in both, carp and eel, whereas BIA is oflimited use for energetic measurements in the same species, in contrast to other reports in the literature...

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

    Directory of Open Access Journals (Sweden)

    D. A. Budika

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-08-27

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

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

    Science.gov (United States)

    Muñoz-Sanz, Agustín

    2012-11-01

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

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

    Science.gov (United States)

    Wehrwein, Peter

    2017-02-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

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

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

    NARCIS (Netherlands)

    Lord, C.M.

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    NARCIS (Netherlands)

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

    2018-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Vladimir V. Kutyrev

    2018-05-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  5. Does nanobiotechnology oversight present a uniquely complex challenge to interagency cooperation?

    International Nuclear Information System (INIS)

    Karkkainen, Bradley C.

    2011-01-01

    Numerous regulatory and oversight challenges exist in the field of nanobiotechnology. Although these challenges may appear novel and complex, similar issues have plagued environmental regulation since the 1970 s. This article argues that complexity, uncertainty, and regulatory gaps are common problems in environmental regulation, and that the lessons learned and progress made during more than 40 years of environmental regulation can serve as a guidepost for addressing nanobiotechnology regulation and oversight issues.

  6. A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans

    International Nuclear Information System (INIS)

    Morpurgo, G.; Puppo, S.; Gualandi, G.; Conti, L.

    1978-01-01

    A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation. (Auth.)

  7. Humanitarian Algorithms : A Codified Key Safety Switch Protocol for Lethal Autonomy

    OpenAIRE

    Nyagudi, Nyagudi Musandu

    2014-01-01

    With the deployment of lethal autonomous weapons, there is the requirement that any such platform complies with the precepts of International Humanitarian Law. Humanitarian Algorithms[9: p. 9] ensure that lethal autonomous weapon systems perform military/security operations, within the confines of International Humanitarian Law. Unlike other existing techniques of regulating lethal autonomy this scheme advocates for an approach that enables Machine Learning. Lethal autonomous weapons must be ...

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

    Science.gov (United States)

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

    2015-05-01

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

  9. Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Miller, S.F. [Dept. of Radiology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Proud, V.K. [Dept. of Genetics, Children' s Hospital of the King' s Daughters, Norfolk (United States); Werner, A.L. [Dept. of Pathology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Field, F.M.; Wilcox, W.F.; Lachman, R.S.; Rimoin, D.L. [International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center, Los Angeles (United States)

    2003-04-01

    Background: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling. Objective: To describe the diagnostic radiographic features seen in Pacman dysplasia, a distinct autosomal recessive, lethal skeletal dysplasia. Materials and methods: We present the fourth reported case of Pacman dysplasia and compare the findings seen in our patient with the three previously described patients. Results: Invariable and variable radiographic findings were seen in all four cases of histologically proven Pacman dysplasia. Conclusion: Pacman dysplasia presents both constant and variable diagnostic radiographic features. (orig.)

  10. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  11. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    International Nuclear Information System (INIS)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E.; Halvorsen, O.J.; Gjelland, K.; Engebretsen, L.

    2001-01-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  12. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.

    1981-01-01

    Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

  13. Chemical and radiation induced late dominant lethal effects in mice

    International Nuclear Information System (INIS)

    Favor, J.; Crenshaw, J.W. Jr.; Soares, E.R.

    1978-01-01

    Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. The authors routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed. (Auth.)

  14. An improved brine shrimp larvae lethality microwell test method.

    Science.gov (United States)

    Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie

    2012-01-01

    This article described an improved brine shrimp larvae lethality microwell test method. A simply designed connecting vessel with alternative photoperiod was used to culture and collect high yield of active Artemia parthenogenetica nauplii for brine shrimp larvae lethality microwell test. Using this method, pure A. parthenogenetica nauplii suspension was easily cultured and harvested with high density about 100-150 larvae per milliliter and the natural mortality was reduced to near zero by elimination of unnecessary artificial disturbance. And its sensitivity was validated by determination of LC(50)-24 h of different reference toxicants including five antitumor agents, two pesticides, three organic pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h over 300 mg/L.

  15. Dominant lethals following administration of tritium (THO) to rat males

    International Nuclear Information System (INIS)

    Yagova, A.; Baev, I.; Bajrakova, A.

    1976-01-01

    Adult rat males were given a single intraperitoneal tritium (THO) injection at 0,01 or 0,001 mCi/g body weight (1/100 or 1/1000 of LDsub(50/30), respectively). Twelve days after treatment each male was mated to 3-5 intact females, and the latter were replaced by fresh ones every 12 following days over a 120-day period. Mated females were killed to score conceptions, corpora lutea, and live and dead embryos. Estimations were made of F 1 prenatal death rate (according to Bateman, 1958) and the frequency of induction of dominant lethal mutations (according to Roehrborn, 1970). The results observed indicated paternal exposure to tritium (THO) to produce dominant lethals both in pre- and post-meiotic germ cells in the rat. The extent of the genetic damage studied was found to depend on the amount of activity administered as well as on the time interval between treatment and conception. (author)

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

    Science.gov (United States)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Aureci Maria Araujo

    1996-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Dragos Mitrofan

    2015-03-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2017-08-07

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

  3. Non-Lethal Weaponry: A Framework for Future Integration

    Science.gov (United States)

    1998-04-01

    community, but was widely popularized by John Naisbitt in his 1982 work, Megatrends . In short, it asserts that much may be learned about a dynamic, but...Notes 1 John Naisbitt, Megatrends : Ten New Directions Transforming Our Lives (New York, NY: Warner Books, Inc., 1982), 3-5. 2 Robert J. Bunker...lethals by opponents of biological and chemical weapons. The use of chemical agents…is seen as a Trojan Horse to circumvent the Chemical Weapons

  4. Genome Replikin Count Predicts Increased Infectivity/Lethality of Viruses

    OpenAIRE

    Samuel Bogoch; Elenore S. Bogoch

    2012-01-01

    The genomes of all groups of viruses whose sequences are listed on Pubmed, specimens since 1918, analyzed by a software from Bioradar UK Ltd., contain Replikins which range in concentration from a Replikin Count (number of Replikins per 100 amino acids) of less than 1 to 30 (see accompanying communications for higher Counts in tuberculosis, malaria, and cancer, associated with higher lethality). Counts of less than 4.0 were found in ‘resting’ virus states; Counts greater than 4....

  5. Spondyloepiphyseal dysplasia congenita. A cause of lethal neonatal dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Macpherson, R.I.; Wood, B.P.

    1980-07-01

    Spondyloepiphyseal dysplasia congenita is a form of primarily short trunk dwarfism, that is manifest at birth but generally has not been regarded as a cause of lethal neonatal dwarfism. Seven neonates with severe dwarfism are presented. The first survived the newborn period, but the other six were early neonatal deaths. All displayed the clinical and radiologic features of spondyloepiphyseal dysplasia congenita. The striking similarities between spondyloepiphyseal dysplasia congenita and achondrogenesis type 2 are discussed.

  6. Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

    International Nuclear Information System (INIS)

    Kaibara, N.; Yokoyama, K.; Nakano, H.

    1983-01-01

    A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity. (orig.)

  7. Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kaibara, N.; Yokoyama, K.; Nakano, H.

    1983-06-01

    A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity.

  8. First diagnosed lethal case of lyssavirus infection in Primorsky krai

    OpenAIRE

    Leonova, G.; Chentsova, I.; Petukhova, S.; Somova, L.; Belikov, S.; Kondratov, I.; Kryilova, N.; Plekhova, N.; Pavlenko, E.; Romanova, E.; Matsak, V.; Smirnov, G.; Novikov, D.

    2010-01-01

    The paper provides data of comprehensive study of lethal case of lyssavirus infection first diagnosed in Yakovlevsky municipal district in Primorsky Krai. The data of epidemiologic analysis (contact with a rattle mouse), clinical picture and results of virologic, morphological and molecular genetic tests allow attributing this case to lyssavirus infection. This is the first diagnosed case of lyssavirus infection in the Siberia and Far East.

  9. Transplantation of bone marrow cells into lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Hermanova, E.

    1978-01-01

    Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

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

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sean M Moore

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

  13. Lethal mutagenesis: targeting the mutator phenotype in cancer.

    Science.gov (United States)

    Fox, Edward J; Loeb, Lawrence A

    2010-10-01

    The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Li, H; Lai, W

    1999-04-01

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

  15. An antivector vaccine protects against a lethal vector-borne pathogen.

    Directory of Open Access Journals (Sweden)

    Milan Labuda

    2006-04-01

    Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

  16. Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).

    Science.gov (United States)

    Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni

    2017-12-05

    Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    Science.gov (United States)

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

  18. Inactivated recombinant plant virus protects dogs from a lethal challenge with canine parvovirus

    DEFF Research Database (Denmark)

    Langeveld, J.P.M.; Brennan, F.R.; Martinez-Torrecuadrada, J.L.

    2001-01-01

    A vaccine based upon a recombinant plant virus (CPMV-PARVO1), displaying a peptide derived from the VP2 capsid protein of canine parvovirus (CPV), has previously been described. To date, studies with the vaccine have utilized viable plant chimaeric particles (CVPs). In this study, CPMV-PARVO1...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pan Tao

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