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Sample records for anthrax spore-induced mortality

  1. Role of visible light-activated photocatalyst on the reduction of anthrax spore-induced mortality in mice.

    Directory of Open Access Journals (Sweden)

    Jyh-Hwa Kau

    Full Text Available BACKGROUND: Photocatalysis of titanium dioxide (TiO(2 substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO(2 substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. Their anti-spore activity against Bacillus anthracis, however, remains to be investigated. We evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Standard plating method was used to determine the inactivation of anthrax spore by visible light-induced photocatalysis. Mouse models were further employed to investigate the suppressive effects of the photocatalysis on anthrax toxin- and spore-mediated mortality. We found that anti-spore activities of visible light illuminated nitrogen- or carbon-doped titania thin films significantly reduced viability of anthrax spores. Even though the spore-killing efficiency is only approximately 25%, our data indicate that spores from photocatalyzed groups but not untreated groups have a less survival rate after macrophage clearance. In addition, the photocatalysis could directly inactivate lethal toxin, the major virulence factor of B. anthracis. In agreement with these results, we found that the photocatalyzed spores have tenfold less potency to induce mortality in mice. These data suggest that the photocatalysis might injury the spores through inactivating spore components. CONCLUSION/SIGNIFICANCE: Photocatalysis induced injuries of the spores might be more important than direct killing of spores to reduce pathogenicity in the host.

  2. Erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor is associated with reduced anthrax-lethal-toxin-induced mortality in mice.

    Directory of Open Access Journals (Sweden)

    Hsin-Hou Chang

    Full Text Available Anthrax lethal toxin (LT, one of the primary virulence factors of Bacillus anthracis, causes anthrax-like symptoms and death in animals. Experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering LT. In this study, the granulocyte colony-stimulating factor (G-CSF was used as a therapeutic agent to ameliorate anthrax-LT- and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF promoted the mobilization of mature erythrocytes to peripheral blood, resulting in a significantly faster recovery from erythrocytopenia. In addition, combined treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore-elicited mortality in mice. Although specific treatments against LT-mediated pathogenesis remain elusive, these results may be useful in developing feasible strategies to treat anthrax.

  3. Anthrax

    Science.gov (United States)

    2009-01-01

    antigen (P A) using immunoglobulin G (lgG) antibodies in response to the bioterrorist anthrax plot in 2001. ELISA proved extremely useful in the...essential for binding to P A. Fusion of this highly conserved N-terminal sequence to other toxins, such as Shiga and diphtheria , can cause toxic...assay, blood cultures, motility tests, enzyme-linked immunosorbent assays ( ELISA ), and fluorescent covalent microsphere immunoassay (FCMIA

  4. Heroin-associated anthrax with minimal morbidity.

    Science.gov (United States)

    Black, Heather; Chapman, Ann; Inverarity, Donald; Sinha, Satyajit

    2017-03-08

    In 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. He subsequently was found to have anthrax. We describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. His full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention.

  5. Anthrax: Diagnosis

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Anthrax Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Anthrax Basic Information Types of Anthrax Cutaneous Anthrax Inhalation ...

  6. Anthrax Vaccine

    Science.gov (United States)

    What is anthrax?Anthrax is a serious disease that can affect both animals and humans. It is caused by bacteria called Bacillus anthracis. People can get anthrax from contact with infected animals, wool, meat, or ...

  7. Anthrax Basics

    Science.gov (United States)

    ... Recommend on Facebook Tweet Share Compartir What is anthrax? Anthrax is a serious infectious disease caused by ... or flu. How do animals get infected with anthrax? Domestic and wild animals such as cattle, sheep, ...

  8. Anthrax: Symptoms

    Science.gov (United States)

    ... EID Journal Articles Anthrax-Related MMWRs Medscape Commentaries Symptoms Language: English Español (Spanish) Recommend on Facebook Tweet ... cause severe illness and even death. Cutaneous anthrax symptoms can include: A group of small blisters or ...

  9. Anthrax Remembered

    Centers for Disease Control (CDC) Podcasts

    2015-08-03

    Dr. John Jernigan and Dr. D. Peter Drotman recall the 2001 anthrax attacks and rapid publication of the landmark paper reporting the initial cases of inhalational anthrax.  Created: 8/3/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/3/2015.

  10. Cutaneous anthrax (image)

    Science.gov (United States)

    Anthrax is caused by the bacteria Bacillus anthracis . While anthrax commonly affects hoofed animals such as sheep and goats, humans may get sick from anthrax, too. The most common type of anthrax infection ...

  11. Pediatric anthrax clinical management.

    Science.gov (United States)

    Bradley, John S; Peacock, Georgina; Krug, Steven E; Bower, William A; Cohn, Amanda C; Meaney-Delman, Dana; Pavia, Andrew T

    2014-05-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as "children") in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults.

  12. Anthrax Pathogenesis.

    Science.gov (United States)

    Moayeri, Mahtab; Leppla, Stephen H; Vrentas, Catherine; Pomerantsev, Andrei P; Liu, Shihui

    2015-01-01

    Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides-protective antigen (PA), lethal factor (LF), and edema factor (EF)-that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.

  13. Anthrax - past, present and future

    Directory of Open Access Journals (Sweden)

    Madle-Samardžija Nadežda D.

    2002-01-01

    Full Text Available History Anthrax has been known since ancient times. Besides some references in the Old Testament, there is evidence of plagues in ancient Egypt, as well as descriptions of the disease by the Roman poet Virgil. Etiology Anthrax is caused by Bacillus anthracis, unmovable, aerobic, gram-positive rods. It forms spores, which can survive for years in the environment. Pathogenesis Capsular polypeptide and anthrax toxin are the principal virulence factors of Bacillus anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor. It is thought that the inflammatory mediator - lethal factor is stored within the macrophage during the early stage of infection. It is rapidly released in large amounts into the blood stream and once the threshold for lysis is reached, it may be the cause of sudden death. Epidemiology Grass-eating animals are usually infected by the bacilli from grass and ground. The disease is transmitted to people by contact with the sick animals or their products, such as wool skin, meat etc. Clinical features Two clinical forms exist: outer cutaneous and inner, including inhalation and gastrointestinal anthrax. While cutaneous anthrax is easily cured, the inner forms have high mortality rates. Diagnosis and differential diagnosis The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should arise suspicion of anthrax. Therapy Hospitalization of patients is mandatory. Bacillus anthracis is susceptible to a number of antibiotics, including penicillin, erythromycin tetracyclines, cephalosporins etc. Prevention General veterinary prevention including vaccination of livestock and control of products is very important. The vaccine consists of anthrax bacillus that is attenuated. The endangered population, such as animal workers and military personnel should be vaccinated

  14. Anthrax as an example of the One Health concept.

    Science.gov (United States)

    Bengis, R G; Frean, J

    2014-08-01

    Anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. It is one of the oldest infectious diseases known; the biblical fifth and sixth plagues (Exodus chapters 7 to 9) that affected first livestock and then humans were probably anthrax. From the earliest historical records until development of an effective vaccine midway through the 20th Century, anthrax was one of the foremost causes of uncontrolled mortality in cattle, sheep, goats, horses and pigs, with 'spill over' into humans, worldwide. With the development of the Sterne spore vaccine, a sharp decline in anthrax outbreaks in livestock occurred during the 1930-1980 era. There were successful national vaccination programmes in many countries during this period, complemented by the liberal use of antibiotics and the implementation of quarantine regulations and carcass disposal. However, a resurgence of this disease in livestock has been reported recently in some regions, where complacency and a false sense of security have hindered vaccination programmes. The epidemiology of anthrax involves an environmental component, as well as livestock, wildlife and human components. This makes anthrax an ideal example for discussion in the One Health context. Many outbreaks of anthrax in wildlife are undetected or unreported, owing to surveillance inadequacies and difficulties. Human disease is generally acquired accidentally during outbreaks of anthrax in domestic livestock and wildlife. The exception is deliberate targeting of humans with anthrax in the course of biowarfare or bioterrorism.

  15. Anthrax undervalued zoonosis

    OpenAIRE

    2010-01-01

    Abstract Anthrax is a non-contagious disease, known since ancient times but it became a matter of global public interest after the bioterrorist attacks in the U.S.A. during the autumn of 2001. The concern of politicians and civil authorities everywhere towards this emergency necessitated a significant research effort and the prevention of new bioterrorist acts. But anthrax is primarily a disease that affects livestock and wildlife; its distribution is worldwide; and it can represen...

  16. Public health and bioterrorism: renewed threat of anthrax and smallpox.

    Science.gov (United States)

    Wallin, Arūne; Luksiene, Zivile; Zagminas, Kestutis; Surkiene, Gene

    2007-01-01

    Bioterrorism is one of the main public health categorical domains. According to sociological analytics, in postmodern society terrorism is one of the real threats of the 21st century. While rare, the use of biological weapons has a long history. Recently, anthrax has been evaluated as one of the most dangerous biological weapons. Naturally occurring anthrax in humans is a disease acquired from contact with anthrax-infected animals or anthrax-contaminated animal products. Usually anthrax infection occurs in humans by three major routes: inhalational, cutaneous, and gastrointestinal. Inhalational anthrax is expected to account for most serious morbidity and most mortality. The clinical presentation of inhalation anthrax has been described as a two-stage illness. Many factors contribute to the pathogenesis of Bacillus anthracis. Antibiotics, anthrax globulin, corticosteroids, mechanical ventilation, vaccine are possible tools of therapy. Smallpox existed in two forms: variola major, which accounted for most morbidity and mortality, and a milder form, variola minor. Smallpox spreads from person to person primarily by droplet nuclei or aerosols expelled from the oropharynx of infected persons and by direct contact. In the event of limited outbreak with few cases, patients should be admitted to the hospital and confined to rooms that are under negative pressure and equipped with high-efficiency particulate air filtration. In larger outbreaks, home isolation and care should be the objective for most patients. Progress in detection, suitable vaccines, postexposure prophylaxis, infection control, and decontamination might be serious tools in fight against the most powerful biological weapon. To assure that the public health and healthcare system can respond to emergencies, the government should direct resources to strengthen the emergency-response system, create medication stockpiles, and improve the public health infrastructure.

  17. Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review.

    Science.gov (United States)

    Pillai, Satish K; Huang, Eileen; Guarnizo, Julie T; Hoyle, Jamechia D; Katharios-Lanwermeyer, Stefan; Turski, Theresa K; Bower, William A; Hendricks, Katherine A; Meaney-Delman, Dana

    2015-01-01

    Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English-language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. A total of 149 cases of systemic anthrax were identified. Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n = 77), survival was greater for those receiving 3 or more antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

  18. Anthrax (Lecture Aids) - USSR .

    Science.gov (United States)

    1961-08-14

    utions (phenol, lysol , etc.) and dies at a temperature of 60-70 C. As opposed to the vegetative form, the anthrax spore is extremely resistant to...external influences. Ord- inary disinfectant solutions (corrosive sublimate, carbolic acid, lysol ) are not used, since they have little effect on

  19. Anthrax lethal and edema toxins in anthrax pathogenesis.

    Science.gov (United States)

    Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H

    2014-06-01

    The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis protein 2 (CMG2) as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.

  20. Methods for neutralizing anthrax or anthrax spores

    Science.gov (United States)

    Sloan, Mark A; Vivekandanda, Jeevalatha; Holwitt, Eric A; Kiel, Johnathan L

    2013-02-26

    The present invention concerns methods, compositions and apparatus for neutralizing bioagents, wherein bioagents comprise biowarfare agents, biohazardous agents, biological agents and/or infectious agents. The methods comprise exposing the bioagent to an organic semiconductor and exposing the bioagent and organic semiconductor to a source of energy. Although any source of energy is contemplated, in some embodiments the energy comprises visible light, ultraviolet, infrared, radiofrequency, microwave, laser radiation, pulsed corona discharge or electron beam radiation. Exemplary organic semiconductors include DAT and DALM. In certain embodiments, the organic semiconductor may be attached to one or more binding moieties, such as an antibody, antibody fragment, or nucleic acid ligand. Preferably, the binding moiety has a binding affinity for one or more bioagents to be neutralized. Other embodiments concern an apparatus comprising an organic semiconductor and an energy source. In preferred embodiments, the methods, compositions and apparatus are used for neutralizing anthrax spores.

  1. Dances with anthrax: wolves (Canis lupus) kill anthrax bacteremic plains bison (Bison bison bison) in southwestern Montana.

    Science.gov (United States)

    Blackburn, Jason K; Asher, Valpa; Stokke, Stephen; Hunter, David L; Alexander, Kathleen A

    2014-04-01

    Bacillus anthracis, the cause of anthrax, was recovered from two plains bison (Bison bison bison) cows killed by wolves (Canis lupus) in Montana, USA, without associated wolf mortality in July 2010. This bison herd experienced an epizootic in summer 2008, killing ∼ 8% of the herd, the first documented in the region in several decades. No wolf deaths were associated with the 2008 event. Surveillance has continued since 2008, with research, ranch, and wildlife personnel diligent during summer. As part of this, we tested wolf-killed bison and elk (Cervus elaphus) for anthrax during the 2010 summer using lateral flow immunochromatographic assays (LFIA). Two bison cows were positive for protective antigen, confirming active bacteremia. The LFIA results were confirmed with traditional bacteriology recovering viable B. anthracis. No wolf fatalities were associated with the bison deaths, despite consuming the meat. Low-level anthrax occurrence in large, rough terrain landscapes remains difficult to detect, particularly if mortality in the herbivore host is not a consequence of infection. In these instances, surveillance of predators with large home ranges may provide a more sensitive indicator of anthrax emergence or reemergence in such systems. Though speculative, it is also possible that anthrax infection in the bison increased predation risk. These results also suggest B. anthracis remains a threat to wildlife and associated livestock in southwestern Montana.

  2. Anthrax Spores under a microscope

    Science.gov (United States)

    2003-01-01

    Anthrax spores are inactive forms of Bacillus anthracis. They can survive for decades inside a spore's tough protective coating; they become active when inhaled by humans. A result of NASA- and industry-sponsored research to develop small greenhouses for space research is the unique AiroCide TiO2 system that kills anthrax spores and other pathogens.

  3. [Anthrax due to deliberate infection

    NARCIS (Netherlands)

    Dissel, J.T. van; Kullberg, B.J.; Berg, P.C. van den; Steenbergen, J.E. van

    2001-01-01

    Anthrax is a zoonosis which is particularly prevalent in cattle, goats and sheep and is caused by Bacillus anthracis, a Gram-positive spore forming aerobic microorganism. The endospores can survive outside of the body for many decades. The natural form of anthrax has a cutaneous, pulmonary and intes

  4. Three eyelid localized cutaneous anthrax cases.

    Science.gov (United States)

    Esmer, Oktay; Karadag, Remzi; Bilgili, Serap Gunes; Gultepe, Bilge; Bayramlar, Huseyin; Karadag, Ayse Serap

    2014-12-01

    Anthrax is primarily seen in the developing countries, but it can be a worldwide medical concern due to bioterrorism threats. Palpebral anthrax is a rare form of cutaneous anthrax. Untreated cutaneous anthrax can be lethal. Patients with palpebral anthrax can develop complications including cicatrisation and ectropion. Thus, anthrax should be considered in differential diagnosis for patients presenting with preseptal cellulitis in high-risk regions. Herein, we report three anthrax cases (with different age) involving eyelids that were cured without any complications due to early diagnosis and treatment.

  5. The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax.

    Science.gov (United States)

    Coggeshall, Kenneth Mark; Lupu, Florea; Ballard, Jimmy; Metcalf, Jordan P; James, Judith A; Farris, Darise; Kurosawa, Shinichiro

    2013-07-01

    Inhalation anthrax is often described as a toxin-mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients.

  6. Surveillance and control of anthrax and rabies in wild herbivores and carnivores in Namibia.

    Science.gov (United States)

    Berry, H H

    1993-03-01

    Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totalling 6,190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible.

  7. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009 (Morbidity and Mortality Weekly Report. Volume 59, Number RR-6, July 23, 2010)

    Science.gov (United States)

    2010-07-23

    Streptococcus pyogenes in children. Antimicrob Agents Chemother 2008;52:2512–20. 220. Rollag Jr H, Midtvedt T, Wetterhus S. Serum levels of penicillin V...contaminated animal products or an infected animal (28). Agricultural cases of anthrax occur among persons who have direct contact with infected sick ...limited to support a regimen of ឬ days. Oral ciprofloxacin, oral doxycycline, and parenteral (IM) penicillin G procaine have been shown to be

  8. Anthrax receptors position the spindle.

    Science.gov (United States)

    Minc, Nicolas; Piel, Matthieu

    2013-01-01

    Spindle orientation plays a pivotal role in tissue morphogenesis. An asymmetric anthrax receptor cap is revealed to promote activation of a formin to orient the spindle along the planar cell polarity (PCP) axis in zebrafish dorsal epiblast cells.

  9. First Autochthonous Coinfected Anthrax in an Immunocompetent Patient

    Directory of Open Access Journals (Sweden)

    Parvaneh Afshar

    2015-01-01

    Full Text Available Cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. The clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. Anthrax is known to be more common in the Middle East and Iran is one of the countries in which the zoonotic form of anthrax may still be encountered. We report a case of a 19-years-old male who used to apply Venetian ceruse on his skin. Venetian ceruse (also known as Spirits of Saturn is an old cosmetic product used for skin whitening traditionally made from sheep’s spinal cord. The patient referred to the Referral Laboratory, Mazandaran University of Medical Sciences, Sari, Iran, with atypical dermatosis, pronounced pain, and oedema of the affected tissue. It was confirmed by both conventional and molecular analysis that culture was a mixture of Bacillus anthracis and Trichophyton interdigitale. The patient was initially treated with ceftriaxone (1000 mg/day for two weeks, gentamicin (1.5–2 mg/kg/day, terbinafine (200 mg/week for one month, and 1% clotrimazole cream (5 weeks two times per day which resulted in gradual improvement. No relapse could be detected after one-year follow-up. Anthrax infection might present a broader spectrum of symptoms than expected by clinicians. These unfamiliar characteristics may lead to delayed diagnosis, inadequate treatment, and higher mortality rate. Clinicians need to be aware of this issue in order to have successful management over this infection.

  10. Cutaneous anthrax cases leading compartment syndrome

    Directory of Open Access Journals (Sweden)

    Emine Parlak

    2013-12-01

    Full Text Available Bacillus anthracis is the causative agent of anthrax. Anthrax is a zoonotic disease with three clinical forms. Clinical forms are skin, gastrointestinal and inhalational anthrax. Cutaneous anthrax is 95% of the cases. Cutaneous anthrax frequently defines itself. Clinical presentation of anthrax may be severe and complicated in some cases. There may seem complications like meningitis, septic shock and compartment syndrome. Compartment Syndrome is a rare complication of cutaneous anthrax and it is life threatening. Physicians working in the endemic area should be aware of this form. In this study, three cases were shown which developed compartment syndrome following cutaneous anthrax. J Microbiol Infect Dis 2013;3(4: 214-217

  11. Anthrax: A Guide for Biology Teachers.

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Presents facts about anthrax so that biology teachers can communicate them to others. Defines anthrax and the nature of bacterial spores. Discusses transmission and clinical presentation as well as prevention, diagnosis, and treatment. Explores the use of anthrax as a biological warfare agent. (Contains 27 references.) (DDR)

  12. Anthrax - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

  13. Investigation of inhalation anthrax case, United States.

    Science.gov (United States)

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  14. Rapid homogenous time-resolved fluorescence (HTRF) immunoassay for anthrax detection.

    Science.gov (United States)

    Cohen, Noam; Mechaly, Adva; Mazor, Ohad; Fisher, Morly; Zahavy, Eran

    2014-05-01

    Infection with Bacillus anthracsis spores induces an acute anthrax disease that can cause casualties and death in untreated cases. Thus rapid diagnosis of anthrax at early stage of the disease is essential to allow an effective treatment. Here we present the development of rapid and sensitive homogenous time-resolved fluorescence (HTRF) immunoassays based on the energy transfer process of europium cryptate (EuK) donor to AlexaFluor647 acceptor. The energy transfer process is limited to d bacteremia in infected hosts, using two monoclonal anti-PA antibodies that specifically recognize two different epitopes on the PA molecule. The assay was sensitive enabling detection of 2 ng/ml PA in the serum of B. anthracsis-infected rabbits in only 15 min assay. Additionally, HTRF assay was developed for the detection of bacterial spores using polyclonal anti-spore antibodies that recognize many epitopes on the bacterial surface. The assay enabled the detection of 2 × 10(6) spores/ml in 30 min assay and was specific, showing no cross reactivity with closely related non-virulent bacillus cereus strain. This study describes the use of the HTRF assay for the detection of both singled-epitope (proteins) and multi-epitope (particles) as rapid, simple and sensitive method that can be used at the time that fast results are needed to allow an effective medical care.

  15. Airing Out Anthrax

    Science.gov (United States)

    2002-01-01

    The AiroCide TiO2 is an air-purifier that kills 93.3 percent of airborne pathogens that pass through it, including Bacillus anthraci, more commonly known as anthrax. It is essentially a spinoff of KES Science & Technology, Inc.'s Bio-KES system, a highly effective device used by the produce industry for ethylene gas removal to aid in preserving the freshness of fruits, vegetables, and flowers. The TiO2-based ethylene removal technology that is incorporated into the company's AiroCide TiO2 and Bio-KES products was first integrated into a pair of plant-growth chambers known as ASTROCULTURE(TM) and ADVANCED ASTROCULTURE(TM). Both chambers have housed commercial plant growth experiments in space on either the Space Shuttle or the International Space Station. The AiroCide TiO2 also has a proven record of destroying 98 percent of other airborne pathogens, such as microscopic dust mites, molds, and fungi. Moreover, the device is a verified killer of Influenza A (flu), E. coli, Staphylococcus aureas, Streptococcus pyogenes, and Mycoplasma pneumoniae, among many other harmful viruses.

  16. Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine.

    Science.gov (United States)

    Kim, Yeon Hee; Kim, Kyung Ae; Kim, Yu-Ri; Choi, Min Kyung; Kim, Hye Kyeong; Choi, Ki Ju; Chun, Jeong-Hoon; Cha, Kiweon; Hong, Kee-Jong; Lee, Na Gyong; Yoo, Cheon-Kwon; Oh, Hee-Bok; Kim, Tae Sung; Rhie, Gi-eun

    2014-01-01

    Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells.

  17. Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax.

    Science.gov (United States)

    Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M

    2015-09-29

    The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay.

  18. Anthrax - Pasteur to the Present

    Science.gov (United States)

    1987-01-01

    Hausler, Jr., H. J. Shadomy (ed.l, ASM Manual of Clinical Microbiology , 4th Edition , American Society for Microbiology , Washington, D.C. 4. Dutz, W. and E...Harrison, L. 14ý et at. 1986. Application of an electro- phoretic iAaunotransblot method for the serologic diagnosis of anthrax. 26th Inttrsci. Conf

  19. Designing Inhibitors of Anthrax Toxin

    Science.gov (United States)

    Nestorovich, Ekaterina M.; Bezrukov, Sergey M.

    2014-01-01

    Introduction Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates, and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded “for the development of multiscale models for complex chemical systems” once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial and error approach to a minimum. The “rational drug design” term is rather comprehensive as it includes all contemporary methods of drug discovery where serendipity and screening are substituted by the information-guided search for new and existing compounds. Successful implementation of these innovative drug discovery approaches is inevitably preceded by learning the physics, chemistry, and physiology of functioning of biological structures under normal and pathological conditions. Areas covered This article provides an overview of the recent rational drug design approaches to discover inhibitors of anthrax toxin. Some of the examples include small-molecule and peptide-based post-exposure therapeutic agents as well as several polyvalent compounds. The review also directs the reader to the vast literature on the recognized advances and future possibilities in the field. Expert opinion Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (PA-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, in our view, the situation is still insecure. The FDA’s animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Besides, unlike PA, which is known to be unstable, LF remains active in cells and in animal tissues for days. Therefore, the effectiveness of the post-exposure treatment of the individuals

  20. Injectional anthrax at a Scottish district general hospital.

    Science.gov (United States)

    Inverarity, D J; Forrester, V M; Cumming, J G R; Paterson, P J; Campbell, R J; Brooks, T J G; Carson, G L; Ruddy, J P

    2015-04-01

    This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

  1. Methods of Eradicating Anthrax - USSR -

    Science.gov (United States)

    2007-11-02

    case of other zoonoses ( brucellosis , rabies, foot- and-mouth disease). Such frequent cases of infection of persons from sick animals indicates an...the diagnosis of anthrax in man« As shown by an analysis of available data, the- overwhelming majority of cases in man have not been confirmed by...bacteriological examination and the diagnosis has been based on clinical and epidemiological or simply clinical data» If the measures indicated are

  2. Oculocutaneous anthrax: detection and treatment

    Directory of Open Access Journals (Sweden)

    Sarada David

    2010-07-01

    Full Text Available Sarada David1, Jayanthi Peter1, Renu Raju2, P Padmaja2, Promila Mohanraj21Department of Ophthalmology, Schell Eye Hospital, Christian Medical College Hospital, Vellore, India; 2Department of Microbiology, Christian Medical College Hospital, Vellore, IndiaAbstract: Anthrax, a zoonotic disease that primarily affects herbivores, has received recent attention as a potential agent of bioterrorism. We report a patient who presented with a 4-day history of pain, watering and difficulty in opening the left upper and lower eyelids, and fever. Clinical examination revealed brawny nonpitting edema with serosanguinous discharge. The history of the death of his sheep 1 week prior to the illness provided the clue to the diagnosis. Although standard cultures of the blood and the serous fluid from the lesion were negative, probably as a result of prior treatment, the diagnosis of cutaneous anthrax was made by a polymerase chain reaction (PCR test of the serous fluid. Serial photographs demonstrating resolution of the lesion with appropriate antibiotic therapy are presented.Keywords: anthrax, polymerase chain reaction, treatment

  3. Neutron-based sterilization of anthrax contamination.

    Science.gov (United States)

    Liu, Bin; Wang, Qingfei

    2006-05-01

    With the anthrax threat becoming a reality, it is very important to have an effective way to sterilize areas contaminated by anthrax. Anthrax spores are the dormant form of the anthrax bacteria. They can germinate in tissues, producing new bacteria that release lethal toxins. Neutrons can be a powerful tool in our defense against anthrax contamination. Neutrons are elementary particles that have no charge, which allows them to be very penetrating, killing the anthrax spores on the surface and inside the containers. So neutrons have an advantage over other forms of radiation if deep penetration is required to kill biological organisms. A Cf neutron source allows for a low cost method of decontamination. It emits most neutrons in the 100 keV to 2 MeV energy regions, and a neutron in this energy region is 20 times more deadly than electrons or gamma rays in killing anthrax spores. If we just consider the first neutron collision with anthrax spores and that all the anthrax spores will not survive at the dose level above 2.0 x 10 Gy, our calculations show that a 0.5-g Cf neutron source within 20 min can generate 1.11 x 10 m fluence neutrons, which is good enough to kill the anthrax spores on the sample. An experimental confirmation of the above results may prove that to achieve 1.11 x 10 m fluence neutrons on the anthrax spore sample, the neutron irradiation time may be reduced dramatically or the Cf neutron source reduced to 0.1 g level or even less. The aim of this paper is to evaluate a feasible way to sterilize the anthrax contamination by using a Cf neutron source. Presently, we are mainly concentrating on the theoretical estimation of neutron fluence to see if the Cf neutron source can deliver enough neutron irradiation dose to kill the anthrax spores. Our future work will focus on experimental confirmation and Monte Carlo simulation by using Geant4 or MCNP codes. At that time, we will consider the effects of the real experimental setup, the shielding materials

  4. Human Cutaneous Anthrax, Georgia 2010–2012

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota

    2014-01-01

    We assessed the occurrence of human cutaneous anthrax in Georgia during 2010–-2012 by examining demographic and spatial characteristics of reported cases. Reporting increased substantially, as did clustering of cases near urban centers. Control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk. PMID:24447721

  5. Treatment of Anthrax Disease Frequently Asked Questions

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  6. Anthrax vaccine associated deaths in miniature horses.

    Science.gov (United States)

    Wobeser, Bruce K

    2015-04-01

    During a widespread anthrax outbreak in Canada, miniature horses were vaccinated using a live spore anthrax vaccine. Several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. During the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.

  7. Human cutaneous anthrax, Georgia 2010-2012.

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota; Blackburn, Jason K

    2014-02-01

    We assessed the occurrence of human cutaneous anthrax in Georgia during 2010--2012 by examining demographic and spatial characteristics of reported cases. Reporting increased substantially, as did clustering of cases near urban centers. Control efforts, including education about anthrax and livestock vaccination, can be directed at areas of high risk.

  8. Anthrax Vaccines: Pasteur to the Present

    Science.gov (United States)

    2006-01-01

    muco- sal immunity would result in superior protection [83, 84]. Strategies to elicit mucosal immunity to anthrax include oral vaccination with...Tafaro, A., Fischer, R., Leppla, S. H., Fujihashi, K. and McGhee, J. R. (2003) Effective mucosal immunity to anthrax: neutralizing antibodies and

  9. Anthrax Outbreaks in Bangladesh, 2009–2010

    Science.gov (United States)

    Chakraborty, Apurba; Khan, Salah Uddin; Hasnat, Mohammed Abul; Parveen, Shahana; Islam, M. Saiful; Mikolon, Andrea; Chakraborty, Ranjit Kumar; Ahmed, Be-Nazir; Ara, Khorsed; Haider, Najmul; Zaki, Sherif R.; Hoffmaster, Alex R.; Rahman, Mahmudur; Luby, Stephen P.; Hossain, M. Jahangir

    2012-01-01

    During August 2009–October 2010, a multidisciplinary team investigated 14 outbreaks of animal and human anthrax in Bangladesh to identify the etiology, pathway of transmission, and social, behavioral, and cultural factors that led to these outbreaks. The team identified 140 animal cases of anthrax and 273 human cases of cutaneous anthrax. Ninety one percent of persons in whom cutaneous anthrax developed had history of butchering sick animals, handling raw meat, contact with animal skin, or were present at slaughtering sites. Each year, Bacillus anthracis of identical genotypes were isolated from animal and human cases. Inadequate livestock vaccination coverage, lack of awareness of the risk of anthrax transmission from animal to humans, social norms and poverty contributed to these outbreaks. Addressing these challenges and adopting a joint animal and human health approach could contribute to detecting and preventing such outbreaks in the future. PMID:22492157

  10. Anthrax Prank Against Teacher Backfires

    Institute of Scientific and Technical Information of China (English)

    梅德名

    2001-01-01

    911事件在美国人心中投下的巨大阴影尚未消失,炭疽热(anthrax)恐怖接踵而至!我国的有关部门已经发布行政命令:禁止邮寄白色粉末。值此“杯弓蛇影”之际,美国佛罗里达州的一位中学生居然“顶风行事”:上课前在讲台上撒了白色粉末……

  11. Anthrax Meningitis - Report Of An Autopsied Case

    Directory of Open Access Journals (Sweden)

    Mahadevan A

    1999-01-01

    Full Text Available Anthrax is a rare cause of hemorrhagic meningitis in man. This report illustrates the characteristic hemorrhagic manifestations in the brain of a patient dying of anthrax meningitis secondary to overwhelming bacteremia. Gross examination of the brain revealed a thick dense subarachnoid hemorrhage with numerous petechial hemorrhages in the cortex. Histologically, meningoencephalitis with vascular necrosis, edema, perivascular cortical hemorrhages and clumps of Gram positive bacilli in the vascular lumen and invading vessel wall were the salient features. The anthrax bacillus was isolated from CSF and brain tissue and further its pathogenecity was confirmed by animal inoculation.

  12. Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

    Directory of Open Access Journals (Sweden)

    Hsin-Hou Chang

    Full Text Available Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs. Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

  13. The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock

    Directory of Open Access Journals (Sweden)

    Peter Q. Eichacker

    2011-09-01

    Full Text Available Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock.

  14. Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models and humans.

    Science.gov (United States)

    Malkevich, Nina V; Hopkins, Robert J; Bernton, Edward; Meister, Gabriel T; Vela, Eric M; Atiee, George; Johnson, Virginia; Nabors, Gary S; Aimes, Ronald T; Ionin, Boris; Skiadopoulos, Mario H

    2014-07-01

    Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.).

  15. Inhalation anthrax in a home craftsman.

    Science.gov (United States)

    Suffin, S C; Carnes, W H; Kaufmann, A F

    1978-09-01

    Inhalation anthrax with complicating subarachnoid hemorrhage due to simultaneous infection with two capsular biotypes of Bacillus anthracis of different virulence for the mouse is reported. The patient, a home craftsman, acquired his infection from imported animal-origin yarn.

  16. List of Contractors to Support Anthrax Remediation

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Lesperance, Ann M.

    2010-05-14

    This document responds to a need identified by private sector businesses for information on contractors that may be qualified to support building remediation efforts following a wide-area anthrax release.

  17. Advances in Anthrax Detection: Overview of Bioprobes and Biosensors.

    Science.gov (United States)

    Kim, Joungmok; Gedi, Vinayakumar; Lee, Sang-Choon; Cho, Jun-Haeng; Moon, Ji-Young; Yoon, Moon-Young

    2015-06-01

    Anthrax is an infectious disease caused by Bacillus anthracis. Although anthrax commonly affects domestic and wild animals, it causes a rare but lethal infection in humans. A variety of techniques have been introduced and evaluated to detect anthrax using cultures, polymerase chain reaction, and immunoassays to address the potential threat of anthrax being used as a bioweapon. The high-potential harm of anthrax in bioterrorism requires sensitive and specific detection systems that are rapid, field-ready, and real-time monitoring. Here, we provide a systematic overview of anthrax detection probes with their potential applications in various ultra-sensitive diagnostic systems.

  18. Anthrax

    Science.gov (United States)

    1984-11-21

    rate, and congested hmorrhagic mucosae (1). Other symptoms -7- may Include ruminal stasis, anorexia, abortion in pregnant cows, discolored or blood...calcareous soils, subject to periodic flooding and formation of small pools which contain decaying plant matter, provide suitable conditions for growth of the

  19. Anthrax

    Science.gov (United States)

    ... Y.: The McGraw-Hill Companies; 2012. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=4. Accessed Feb. 25, ... N.Y.: The McGraw-Hill Companies; 2006. http://accessmedicine.mhmedical.com/content.aspx?bookid=366&Sectionid=39825485. ...

  20. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    Science.gov (United States)

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.

  1. 9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Anthrax Spore Vaccine-Nonencapsulated. 113.66 Section 113.66 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore...

  2. Anthrax toxin-induced rupture of artificial lipid bilayer membranes

    Science.gov (United States)

    Nablo, Brian J.; Panchal, Rekha G.; Bavari, Sina; Nguyen, Tam L.; Gussio, Rick; Ribot, Wil; Friedlander, Art; Chabot, Donald; Reiner, Joseph E.; Robertson, Joseph W. F.; Balijepalli, Arvind; Halverson, Kelly M.; Kasianowicz, John J.

    2013-08-01

    We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.

  3. Serological anthrax surveillance in wild boar (Sus scrofa) in Ukraine.

    Science.gov (United States)

    Bagamian, Karoun H; Skrypnyk, Artem; Rodina, Yana; Bezymennyi, Maksym; Nevolko, Oleg; Skrypnyk, Valeriy; Blackburn, Jason K

    2014-08-01

    Anthrax, caused by Bacillus anthracis, is an acute disease affecting wildlife, livestock, and humans worldwide, although its impact on these populations is underappreciated. In Ukraine, surveillance is passive, and anthrax is often detected in livestock. However, wildlife is not subject to surveillance, although anthrax deaths (such as in wild boar, Sus scrofa) have been documented. The wild boar is a plentiful and widespread species in Ukraine and is frequently hunted. We initiated a screening study testing Ukrainian wild boar blood samples for antibodies to B. anthracis. We mapped results relative to known livestock anthrax hotspots. We discovered evidence of exposure in wild boar up to 35 km from livestock anthrax hotspots and over 400 km from previous anthrax reports in boars. We make recommendations about using wildlife species as biosentinels for anthrax in Ukraine.

  4. [Female patient with cutaneous anthrax in Belgium

    NARCIS (Netherlands)

    Gyssens, I.C.J.; Weyns, D.; Kullberg, B.J.; Ursi, J.P.

    2001-01-01

    A 23-year-old Turkish woman was admitted with an infection of the left thumb. The clinical picture was typical for cutaneous anthrax. Microbiological tests confirmed the diagnosis 'infection by Bacillus anthracis'. She recovered when treated with penicillin, although later tests revealed that the ba

  5. Periorbital cellulitis due to cutaneous anthrax.

    Science.gov (United States)

    Gilliland, Grant; Starks, Victoria; Vrcek, Ivan; Gilliland, Connor

    2015-12-01

    Virgil's plague of the ancient world, Bacillus anthracis, is rare in developed nations. Unfortunately rural communities across the globe continue to be exposed to this potentially lethal bacterium. Herein we report a case of periorbital cutaneous anthrax infection in a 3-year-old girl from the rural area surrounding Harare, Zimbabwe with a brief review of the literature.

  6. An old friend: Anthrax in the Netherlands

    NARCIS (Netherlands)

    Koene, M.G.J.; Rosa, De M.; Spierenburg, M.A.H.; Jacobi, A.; Roest, H.I.J.

    2015-01-01

    In November 2013, bones covered with quicklime were discovered at a construction site near Nijmegen. According to regulations samples were sent to the national reference laboratory (Central Veterinary Institute, CVI), based on the suspicion of anthrax. Laboratory testing confirmed the presence of Ba

  7. Molecular determinants for a cardiovascular collapse in anthrax.

    Science.gov (United States)

    Brojatsch, Jurgen; Casadevall, Arturo; Goldman, David L

    2014-01-01

    Bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. As blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. The anthrax bacterium and the anthrax toxins trigger multi-organ failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. A recent study using mice that either lacked the anthrax toxin receptor in specific cells and corresponding mice expressing the receptor in specific cell types demonstrated that cardiovascular cells are critical for disease mediated by anthrax lethal toxin. These studies are consistent with involvement of the cardiovascular system, and with an increase of cardiac failure markers observed in human anthrax and in animal models using B. anthracis and anthrax toxins. This review discusses the current state of knowledge regarding the pathophysiology of anthrax and tries to provide a mechanistic model and molecular determinants for the circulatory shock in anthrax.

  8. Efficacy of ETI-204 monoclonal antibody as an adjunct therapy in a New Zealand white rabbit partial survival model for inhalational anthrax.

    Science.gov (United States)

    Biron, Bethany; Beck, Katie; Dyer, David; Mattix, Marc; Twenhafel, Nancy; Nalca, Aysegul

    2015-04-01

    Inhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. The Bacillus anthracis antitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals.

  9. Meningoencephalitis due to anthrax: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yildirim, Hanefi; Koc, Mustafa; Murat, Ayse [Firat University, Department of Radiology, Elazig (Turkey); Kabakus, Nimet; Incekoey Girgin, Feyza [Firat University, Department of Paediatric Neurology, Elazig (Turkey)

    2006-11-15

    Anthrax is primarily a disease of herbivores, but it also causes cutaneous, respiratory and gastrointestinal infections in humans. Bacillus anthracis is an uncommon cause of meningitis and generally produces a haemorrhagic meningoencephalitis. We present the CT and MR findings of anthrax meningoencephalitis due to the cutaneous form of anthrax in a 12-year-old boy. They showed focal intracerebral haemorrhage with leptomeningeal enhancement. (orig.)

  10. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  11. New insights into gastrointestinal anthrax infection.

    Science.gov (United States)

    Owen, Jennifer L; Yang, Tao; Mohamadzadeh, Mansour

    2015-03-01

    Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection.

  12. Challenges in Disposing of Anthrax Waste

    Energy Technology Data Exchange (ETDEWEB)

    Lesperance, Ann M.; Stein, Steven L.; Upton, Jaki F.; Toomey, Christopher

    2011-09-01

    Disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. While many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. The Interagency Biological Restoration Demonstration’s (IBRD) purpose was to holistically assess all aspects of an anthrax incident and assist the development of a plan for long-term recovery. In the case of wide-area anthrax contamination and the follow-on response and recovery activities, a significant amount of material will require decontamination and disposal. Accordingly, IBRD facilitated the development of debris management plans to address contaminated waste through a series of interviews and workshops with local, state, and federal representatives. The outcome of these discussion was the identification of three primary topical areas that must be addressed: 1) Planning; 2) Unresolved research questions, and resolving regulatory issues.

  13. Anthrax phylogenetic structure in Northern Italy

    Directory of Open Access Journals (Sweden)

    Corrò Michela

    2011-07-01

    Full Text Available Abstract Background Anthrax has almost disappeared from mainland Europe, except for the Mediterranean region where cases are still reported. In Central and South Italy, anthrax is enzootic, but in the North there are currently no high risk areas, with only sporadic cases having been registered in the last few decades. Regional genetic and molecular characterizations of anthrax in these regions are still lacking. To investigate the potential molecular diversity of Bacillus anthracis in Northern Italy, canonical Single nucleotide polymorphism (canSNP and Multilocus variable number tandem repeat analysis (MLVA genotyping was performed against all isolates from animal outbreaks registered in the last twenty years in the region. Findings Six B. anthracis strains were analyzed. The canSNP analysis indicates the presence of three sublineages/subgroups each of which belong to one of the 12 worldwide CanSNP genotypes: B.Br.CNEVA (3 isolates, A.Br.005/006 (1 isolates and A.008/009 (2 isolate. The latter is the dominant canSNP genotype in Italy. The 15-loci MLVA analysis revealed five different genotypes among the isolates. Conclusions The major B branch and the A.Br.005/006 were recovered in the Northeast region. The genetic structure of anthrax discovered in this area differs from the rest of the country, suggesting the presence of a separate and independent B. anthracis molecular evolution niche. Although the isolates analyzed in this study are limited in quantity and representation, these results indicate that B. anthracis genetic diversity changes around the Alps.

  14. An Outbreak Of Human Anthrax : A Report Of 15 Cases Of Cutaneous Anthrax

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2000-01-01

    Full Text Available Anthrax, a zoonotic illness of herbivorous animals has caused epidemics in livestock and in man since antiquity. In India, the disease continues to be endemic, resulting in a few sporadic cases and outbreaks in human population. Such an outbreak was noted at our institute. Clinical and laboratory data of 15 cases of cutaneous anthrax recorded between July 1998 to June 2000 at the Department of Dermatology and STD. JIPMER hospital, Pondicherry was reviewed. There were 8 males and 7 females in our series of 15, with a mean age of 20.3 years (range 11 months to 56 years. The children (10 outnumbered the adults (5. In most of the cases (9 there was history of death of cattle, sheep or goat in the house or in the neighbourhood. The commonest site of cutaneous anthrax was face (7 cases. Regional lymphadenitis occurred in one case and systemic features like fever in four cases. Majority of our cases responded favourably to crystalline penicillin. Smear taken from the vesicle fluid and eschar demonstrated typical large and thick Gram positive bacilli singly or in short chains. The organism could be cultured from cutaneous lesion in six cases only and blood culture was positive for Bacillus anthracis in one case. Cutaneous anthrax is the commonest form of human anthrax. There is increasing evidence to suggest that files and mosquitoes play a role in the transmission of Bacillus anthracis to human beings. Since 20% of untreated cases of cutaneous anthrax develop bacteraemia which leads to rapid death, it is important that the disease is recognized and treated earnestly.

  15. Anthrax toxins induce shock in rats by depressed cardiac ventricular function.

    Directory of Open Access Journals (Sweden)

    Linley E Watson

    Full Text Available Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx and edema toxin (EdTx to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA toxin component at various time points after infusion. Peak serum levels of PA were in the microg/mL range with half-lives of 10-20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the microg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.

  16. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    Institute of Scientific and Technical Information of China (English)

    Serguei; G; Popov; Taissia; G; Popova; Fatah; Kashanchi; Charles; Bailey

    2011-01-01

    AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.

  17. Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

    Science.gov (United States)

    2007-11-02

    Dendritic Cells Endocytose Bacillus anthracis Spores: Implications for Anthrax Pathogenesis1 Katherine C. Brittingham,* Gordon Ruthel,* Rekha G...germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign...COVERED - 4. TITLE AND SUBTITLE Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis, The Journal of

  18. Recent Developments in Anti-dotes Against Anthrax.

    Science.gov (United States)

    Dhasmana, Neha; Singh, Lalit K; Bhaduri, Asani; Misra, Richa; Singh, Yogendra

    2014-01-01

    The etiologic agent of disease anthrax, Bacillus anthracis, causes recurrent outbreaks among the livestock and intermittent infections in humans across the world. Controlling animal infections by vaccination can minimize the incidence of disease in humans. Prevention of anthrax in occupationally exposed personnel is achieved through vaccination with either live spores or precipitates of culture supernatants from attenuated strains of B. anthracis. However, anthrax vaccination of the large human population is impractical as well as inappropriate. Broad-range antibiotics like amoxicillin, ciprofloxacin, clindamycin, streptomycin, and penicillin G are recommended for the treatment of human anthrax infections, but the threat of antibiotic resistant strains always remains. Moreover, in the absence of any specific symptom (s) during early infection, the diagnosis of anthrax is delayed causing elevated levels of anthrax toxin component which could be fatal. For these reasons, there is a need to develop new antimicrobial agents against virulent B. anthracis to effectively combat this fatal pathogen. Over the last two decades, extensive studies have been carried out to develop specific inhibitors against virulence factors of B. anthracis such as capsule, protective antigen, lethal factor and edema factor. Research has also been focused in developing inhibitors of anthrax toxin receptors (including the use of receptor decoys) and host furin endoproteases which are required for activation of toxin. This review highlights the recent progress made in developing the diverse countermeasures for anthrax infections targeting B. anthracis virulence factors and their counterparts in host.

  19. Two anthrax cases with soft tissue infection, severe oedema and sepsis in Danish heroin users

    DEFF Research Database (Denmark)

    Russell, Lene; Pedersen, Michael; Jensen, Andreas V

    2013-01-01

    Anthrax had become extremely rare in Europe, but in 2010 an outbreak of anthrax among heroin users in Scotland increased awareness of contaminated heroin as a source of anthrax. We present the first two Danish cases of injectional anthrax and discuss the clinical presentations, which included both...

  20. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Science.gov (United States)

    Laws, Thomas R; Kuchuloria, Tinatin; Chitadze, Nazibriola; Little, Stephen F; Webster, Wendy M; Debes, Amanda K; Saginadze, Salome; Tsertsvadze, Nikoloz; Chubinidze, Mariam; Rivard, Robert G; Tsanava, Shota; Dyson, Edward H; Simpson, Andrew J H; Hepburn, Matthew J; Trapaidze, Nino

    2016-01-01

    Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  1. A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines.

    Directory of Open Access Journals (Sweden)

    Thomas R Laws

    Full Text Available Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees or anti-LF (in AVP vaccinees antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens.

  2. The Effect of Anthrax Bioterrorism on Emergency Department Presentation

    Directory of Open Access Journals (Sweden)

    Rodriguez, Robert M

    2005-01-01

    Full Text Available Study Objective: From September through December 2001, 22 Americans were diagnosed with anthrax, prompting widespread national media attention and public concern over bioterrorism. The purpose of this study was to determine the effect of the threat of anthrax bioterrorism on patient presentation to a West Coast emergency department (ED. Methods: This survey was conducted at an urban county ED in Oakland, CA between December 15, 2001 and February 15, 2002. During random 8-hour blocks, all adult patients presenting for flu or upper respiratory infection (URI symptoms were surveyed using a structured survey instrument that included standard visual numerical and Likert scales. Results: Eighty-nine patients were interviewed. Eleven patients (12% reported potential exposure risk factors. Eighty percent of patients watched television, read the newspaper, or listened to the radio daily, and 83% of patients had heard about anthrax bioterrorism. Fifty-five percent received a chest x-ray, 10% received either throat or blood cultures, and 28% received antibiotics. Twenty-one percent of patients surveyed were admitted to the hospital. Most patients were minimally concerned that they may have contracted anthrax (mean=3.3±3.3 where 0=no concern and 10=extremely concerned. Patient concern about anthrax had little influence on their decision to visit the ED (mean=2.8±3.0 where 0=no influence and 10=greatly influenced. Had they experienced their same flu or URI symptoms one year prior to the anthrax outbreak, 91% of patients stated they would have sought medical attention. Conclusions: After considerable exposure to media reports about anthrax, most patients in this urban West Coast ED population were not concerned about anthrax infection. Fear of anthrax had little effect on decisions to come to the ED, and most would have sought medical help prior to the anthrax outbreak.

  3. Risk Assessment of Anthrax Threat Letters

    Science.gov (United States)

    2001-09-01

    risk. Résumé Depuis quelques années, il arrive de plus en plus souvent que des lettres censées contenir l’agent de la maladie du charbon (ou...Depuis quelques années, il arrive de plus en plus souvent que des lettres censées contenir l’agent de la maladie du charbon (ou anthrax) soient...Contracting Agency : Tasking Agency: 9. ORIGINATORS DOCUMENT NO. Technical Report DRES-TR- 2001-048 10. CONTRACT GRANT AND/OR PROJECT NO. 11

  4. Injectional anthrax - new presentation of an old disease.

    Science.gov (United States)

    Berger, T; Kassirer, M; Aran, A A

    2014-08-14

    Bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis. Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout Europe; before 2009 only one case was reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive review of the literature and information derived from different reporting systems until 31 December 2013. Overall 70 confirmed cases were reported, with 26 fatalities (37% case fatality rate).The latest two confirmed cases occurred in March 2013. Thirteen case reports have been published,describing 18 confirmed cases. Sixteen of these presented as a severe soft tissue infection that differed clinically from cutaneous anthrax, lacked the characteristic epidemiological history of animal contact and ten cases required complimentary surgical debridement. These unfamiliar characteristics have led to delays of three to 12 days in diagnosis, inadequate treatment and a high fatality rate. Clinicians' awareness of this recently described clinical entity is key for early 'and successful management of patients.

  5. A Case of Fatal Gastrointestinal Anthrax in North Eastern Iran

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Hashemi

    2015-01-01

    Full Text Available Background. Bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. They are ubiquitous in the environmental sources. Bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. The gastrointestinal (GI anthrax develops after eating contaminated meat. In this paper we report septic intestinal anthrax. Case Presentation. We report an isolation of Bacillus anthracis from blood culture of patient with intestinal anthrax. Bacillus anthracis was isolated from a blood culture of a 34-year-old man who had a history of severe abdominal pain, bloody diarrhea, nausea, vomiting, fever, sweating, and lethargy within 4 to 5 days after eating the meat of domestic goat. He had evidence of severe infection and septic shock and did not respond to treatments and subsequently expired 9 hours after hospitalization. Conclusion. Gastrointestinal anthrax is characterized by rapid onset, fever, and septicemia. Rapid diagnosis and prompt initiation of antibiotic therapy can help in survival. Most of previous cases of septicemic anthrax were related to injection drug users but, in our case, septicemia occurred after gastrointestinal anthrax.

  6. Human anthrax outbreak associated with livestock exposure: Georgia, 2012.

    Science.gov (United States)

    Navdarashvili, A; Doker, T J; Geleishvili, M; Haberling, D L; Kharod, G A; Rush, T H; Maes, E; Zakhashvili, K; Imnadze, P; Bower, W A; Walke, H T; Shadomy, S V

    2016-01-01

    Human anthrax cases reported in the country of Georgia increased 75% from 2011 (n = 81) to 2012 (n = 142). This increase prompted a case-control investigation using 67 culture- or PCR-confirmed cases and 134 controls matched by residence and gender to investigate risk factor(s) for infection during the month before case onset. Independent predictors most strongly associated with disease in the multivariable modelling were slaughtering animals [odds ratio (OR) 7·3, 95% confidence interval (CI) 2·9-18·1, P 1 km; 15 (12%) of 125 had sick livestock; and 11 (9%) of 128 respondents reported finding dead livestock. We recommend joint public health and veterinary anthrax case investigations to identify areas of increased risk for livestock anthrax outbreaks, annual anthrax vaccination of livestock in those areas, and public awareness education.

  7. Screen-printed fluorescent sensors for rapid and sensitive anthrax biomarker detection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Inkyu; Oh, Wan-Kyu; Jang, Jyongsik, E-mail: jsjang@plaza.snu.ac.kr

    2013-05-15

    Highlights: •We fabricated flexible anthrax sensors with a simple screen-printing method. •The sensors selectively detected B. anthracis biomarker. •The sensors provide the visible alarm against anthrax attack. -- Abstract: Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide–ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax.

  8. Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

    Science.gov (United States)

    Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana

    2015-01-01

    Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax

  9. Deletion modification enhances anthrax specific immunity and protective efficacy of a hepatitis B core particle-based anthrax epitope vaccine.

    Science.gov (United States)

    Yin, Ying; Zhang, Sheng; Cai, Chenguang; Zhang, Jun; Dong, Dayong; Guo, Qiang; Fu, Ling; Xu, Junjie; Chen, Wei

    2014-02-01

    Protective antigen (PA) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. Previously, we found that the 2β2-2β3 loop of PA contains a dominant neutralizing epitope, the SFFD. We successfully inserted the 2β2-2β3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein. The resulting fusion protein, termed HBc-N144-PA-loop2 (HBcL2), can effectively produce anthrax specific protective antibodies in an animal model. However, the protective immunity caused by HBcL2 could still be improved. In this research, we removed amino acids 79-81 from the HBc MIR of the HBcL2. This region was previously reported to be the major B cell epitope of HBc, and in keeping with this finding, we observed that the short deletion in the MIR not only diminished the intrinsic immunogenicity of HBc but also stimulated a higher titer of anthrax specific immunity. Most importantly, this deletion led to the full protection of the immunized mice against a lethal dose anthrax toxin challenge. We supposed that the conformational changes which occurred after the short deletion and foreign insertion in the MIR of HBc were the most likely reasons for the improvement in the immunogenicity of the HBc-based anthrax epitope vaccine.

  10. Antiplatelet activities of anthrax lethal toxin are associated with suppressed p42/44 and p38 mitogen-activated protein kinase pathways in the platelets.

    Science.gov (United States)

    Kau, Jyh-Hwa; Sun, Der-Shan; Tsai, Wei-Jern; Shyu, Huey-Fen; Huang, Hsin-Hsien; Lin, Hung-Chi; Chang, Hsin-Hou

    2005-10-15

    Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.

  11. Anthrax Vaccine as a Component of the Strategic National Stockpile: A Dilemma for Homeland Security

    Science.gov (United States)

    2009-12-01

    as a prophylaxis for anthrax infection. Instead, the CDC encourages the use of antibiotics, such as penicillin , ciprofloxacin, and doxycycline, as...discovered “ hypersensitivity pneumonitis following anthrax vaccination,” warning physicians to be attentive to “vaccine related complications” (Timmer...anthrax vaccine as a possible cause of hypersensitivity pneumonitis after anthrax vaccination (Oransky, 2003, p. 543). In summary, while some literature

  12. 9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anaplasmosis, anthrax, babesiosis... DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.10 Anaplasmosis, anthrax... condemned: (1) Anthrax. (2) Blackleg. (3) Unhealed vaccine lesions (vaccinia). (4) Strangles. (5)...

  13. Investigation and control of anthrax outbreak at the human-animal interface, Bhutan, 2010.

    Science.gov (United States)

    Thapa, Nirmal K; Tenzin; Wangdi, Karma; Dorji, Tshering; Migma; Dorjee, Jambay; Marston, Chung K; Hoffmaster, Alex R

    2014-09-01

    In 2010, we investigated anthrax outbreak in Bhutan. A total of 43 domestic animals died, and cutaneous anthrax developed in 9 persons, and 1 died. All affected persons had contact with the carcasses of infected animals. Comprehensive preparedness and response guidelines are needed to increase public awareness of anthrax in Bhutan.

  14. Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

    Directory of Open Access Journals (Sweden)

    Chung K Marston

    Full Text Available Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1. This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA, and lethal toxin neutralization activity.

  15. Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar.

    Science.gov (United States)

    Marston, Chung K; Ibrahim, Hisham; Lee, Philip; Churchwell, George; Gumke, Megan; Stanek, Danielle; Gee, Jay E; Boyer, Anne E; Gallegos-Candela, Maribel; Barr, John R; Li, Han; Boulay, Darbi; Cronin, Li; Quinn, Conrad P; Hoffmaster, Alex R

    2016-01-01

    Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity.

  16. Factors associated with repeated outbreak of anthrax in Bangladesh: qualitative and quantitative study

    Directory of Open Access Journals (Sweden)

    Jayedul Hassan

    2015-06-01

    Full Text Available Anthrax, caused by Bacillus anthracis is an acute, febrile disease of warm blooded animals including humans. Social norms and poverty in addition to climatic factors such as soil conditions, seasons of year, ambient temperature and rainfall influence the persistence of the B. anthracis and anthrax outbreaks. The present study was designed to reveal the factors influencing the repeated outbreak of anthrax in Bangladesh. Considering the previous outbreaks of anthrax, Sirajganj, Bogra, Kushtia, Tangail and Mymensingh districts of Bangladesh were selected for this study. To elucidate the factors, qualitative data relating to the animal management, knowledge and behavior of the people; and quantitative data relating to soil conditions, ambient temperature and rainfall were acquired, and analyzed critically. Based on the outbreak histories, a year was divided into two seasons, anthrax prone season (May-November and anthrax dry season (December-April. Anthrax spores could be isolated from 11.67% (n=14/120 of the soil samples collected from the study areas. The present study revealed that poor knowledge, lack of awareness, improper carcass disposal, inadequate vaccination, high Ca content and moisture in the soil along with high ambient temperature and rainfall during the anthrax prone season were the possible influencing factors of repeated outbreaks of anthrax in the study areas. Intensive propaganda to create public awareness of anthrax together with proper vaccination may reduce anthrax outbreaks in Bangladesh.

  17. Space Technology to Device that Destroys Pathogens Such As Anthrax

    Science.gov (United States)

    2002-01-01

    This is a photo of a technician at KES Science and Technology Inc., in Kernesaw, Georgia, assembling the AiroCide Ti02, an anthrax-killing device about the size of a small coffee table. The anthrax-killing air scrubber, AiroCide Ti02, is a tabletop-size metal box that bolts to office ceilings or walls. Its fans draw in airborne spores and airflow forces them through a maze of tubes. Inside, hydroxyl radicals (OH-) attack and kill pathogens. Most remaining spores are destroyed by high-energy ultraviolet photons. Building miniature greenhouses for experiments on the International Space Station has led to the invention of this device that annihilates anthrax, a bacteria that can be deadly when inhaled. The research enabling the invention started at the University of Wisconsin's (Madison) Center for Space Automation and Robotics (WCSAR), one of 17 NASA Commercial Space Centers. A special coating technology used in this anthrax-killing invention is also being used inside WCSAR-built plant growth units on the International Space Station. This commercial research is managed by the Space Product Development Program at the Marshall Space Flight Center.

  18. Anthrax toxin receptor 2-dependent lethal toxin killing in vivo.

    Directory of Open Access Journals (Sweden)

    Heather M Scobie

    2006-10-01

    Full Text Available Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2 have a related integrin-like inserted (I domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis.

  19. Cutaneous anthrax of the hand: Some clinical observations

    Directory of Open Access Journals (Sweden)

    Tuncali Dogan

    2004-01-01

    Full Text Available CONTEXT: Anthrax is a very rare disease in Europe and the United States. AIM: A case of cutaneous anthrax of the hand with a wide skin defect is presented and some clinical observations highlighted. CASE REPORT: A 56-year-old male patient with cutaneous anthrax attended our infectious diseases department with a swelling up to the upper arm. An urgent fasciotomy was undertaken with a diagnosis of compartment syndrome. A black eschar had formed on the dorsal surface of the hand. A superficial tangential escharectomy was performed. RESULTS: Viable fibrous tissue, about 4 to 5 mm in thickness over the extensor tendons, was found under the eschar. At the postoperative 2-year follow-up, remarkable healing was observed via skin grafting. CONCLUSIONS: Hand surgeons should be cautious against the compartment syndrome that may accompany cutaneous anthrax of the hand. A consistent viable fibrous tissue can be found below the eschar. The mechanism for the involvement of the hand dorsum needs further concern.

  20. AN OUTBREAK OF CUTANEOUS ANTHRAX IN TRIBAL AREAS OF VISAKHAPATNAM

    Directory of Open Access Journals (Sweden)

    G. Ajay Kumar

    2016-08-01

    Full Text Available BACKGROUND Anthrax is a disease of herbivorous animals. Humans incidentally acquire the cutaneous disease by handling infected dead animals and their products. Sporadic cases of human anthrax have been reported from Southern India. METHODS Fifteen tribal men, one woman, one child from various places near Paderu presented with painless ulcers associated with vesiculation and oedema of the surrounding skin on the extremities without any constitutional symptoms. There was a history of slaughtering and consumption of a dead goat ten days - 2 weeks prior to the development of skin lesions. Three days later another 19 members came from the same area with same complaints. Clinically, cutaneous anthrax was suspected and smears, swabs, and punch biopsies were taken for culture and identification by Polymerase Chain Reaction (PCR. All the cases were treated with intravenous antibiotics followed by oral antibiotics. Appropriate health authorities were alerted and proper control measures were employed. RESULTS Smears from the cutaneous lesions of some patients were found to be positive for Bacillus anthracis and this was confirmed by polymerase chain reaction. All the cases responded to antibiotics. CONCLUSION We report thirty six cases of cutaneous anthrax in a non-endemic district, Visakhapatnam, Andhra Pradesh.

  1. Growth medium for the rapid isolation and identification of anthrax

    Science.gov (United States)

    Kiel, Johnathan L.; Parker, Jill E.; Grubbs, Teri R.; Alls, John L.

    2000-07-01

    Anthrax has been recognized as a highly likely biological warfare or terrorist agent. The purpose of this work was to design a culture technique to rapidly isolate and identify `live' anthrax. In liquid or solid media form, 3AT medium (3-amino-L-tyrosine, the main ingredient) accelerated germination and growth of anthrax spores in 5 to 6 hours to a point expected at 18 to 24 hours with ordinary medium. During accelerated growth, standard definitive diagnostic tests such as sensitivity to lysis by penicillin or bacteriophage can be run. During this time, the bacteria synthesized a fluorescent and thermochemiluminescent polymer. Bacteria captured by specific antibody are, therefore, already labeled. Because living bacteria are required to generate the polymer, the test converts immunoassays for anthrax into viability assays. Furthermore, the polymer formation leads to the death of the vegetative form and non-viability of the spores produced in the medium. By altering the formulation of the medium, other microbes and even animal and human cells can be grown in it and labeled (including viruses grown in the animal or human cells).

  2. America’s Food: Does Anthrax Pose A Threat?

    Science.gov (United States)

    2002-04-01

    1.htm. 17 Jernigan. 18 Ibid. 19 Ibid. 20 Ibid. 21 Borio, Luciana ; et al. “Death Due to Bioterrorism-Related Inhalational Anthrax.” JAMA, Vol...13 December 2001. On-line. Internet, 4 March 2002. Available from http://www.ift.org/press/releases/terrorism/shtml. Borio, Luciana ; et al. “Death

  3. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.

    Science.gov (United States)

    Hendricks, Katherine A; Wright, Mary E; Shadomy, Sean V; Bradley, John S; Morrow, Meredith G; Pavia, Andy T; Rubinstein, Ethan; Holty, Jon-Erik C; Messonnier, Nancy E; Smith, Theresa L; Pesik, Nicki; Treadwell, Tracee A; Bower, William A

    2014-02-01

    The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

  4. Vaccine-induced protection against anthrax in cheetah (Acinonyx jubatus) and black rhinoceros (Diceros bicornis).

    Science.gov (United States)

    Turnbull, P C B; Tindall, B W; Coetzee, J D; Conradie, C M; Bull, R L; Lindeque, P M; Huebschle, O J B

    2004-09-03

    Institution of a policy of vaccination in endangered species with a vaccine not previously administered to it cannot be undertaken lightly. This applies even more in the case of cheetah (Acinonyx jubatus) with their unusually monomorphic gene pool and the potential restrictions this places on their immune responses. However, the recently observed mortalities from anthrax in these animals in the Etosha National Park, Namibia, made it imperative to evaluate vaccination. Black rhinoceros (Diceros bicornis), another endangered species in the park, have been vaccinated for over three decades but the effectiveness of this has never been evaluated. Passive protection tests in A/J mice using sera from 12 cheetahs together with enzyme immunoassay indicated that cheetah are able to mount seemingly normal primary and secondary humoral immune responses to the Sterne 34F2 live spore livestock vaccine. Overall protection rates in mice injected with the sera rose and fell in concert with rises and declines in antibody titres, although fine analysis showed that the correlation between titre and protection was complex. Once a high level of protection (96% of mice 1 month after a second booster in the cheetahs) had been achieved, the duration of substantial protection appeared good (60% of the mice 5 months after the second booster). Protection conferred on mice by sera from three of four vaccinated rhino was almost complete, but, obscurely, none of the mice receiving serum from the fourth rhino were protected. Sera from three park lions with naturally acquired high antibody titres, included as controls, also conferred high levels of protection. For the purposes of wildlife management, the conclusions were that vaccination of cheetah with the standard animal anthrax vaccine causes no observable ill effect in the animals and does appear to confer protective immunity. At least one well-separated booster does appear to be desirable. Vaccination of rhino also appears to be justified

  5. Anthrax vaccination induced anti-lethal factor IgG: fine specificity and neutralizing capacity.

    Science.gov (United States)

    Crowe, Sherry R; Garman, Lori; Engler, Renata J M; Farris, A Darise; Ballard, Jimmy D; Harley, John B; James, Judith A

    2011-05-09

    The efficacy biomarker of the currently licensed anthrax vaccine (AVA) is based on quantity and neutralizing capacity of anti-protective antigen (anti-PA) antibodies. However, animal studies have demonstrated that antibodies to lethal factor (LF) can provide protection against in vivo bacterial spore challenges. Improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin preparations to treat and prevent inhalation anthrax morbidity and mortality. This study (n=1000) was designed to identify AVA vaccinated individuals who generate neutralizing antibodies and to determine what specificities correlate with protection. The number of vaccine doses, years post vaccination, and PA titer were associated with in vitro neutralization, reinforcing previous reports. In addition, African American individuals had lower serologic neutralizing activity than European Americans, suggesting a genetic role in the generation of these neutralizing antibodies. Of the vaccinated individuals, only 69 (6.9%) had moderate levels of anti-LF IgG compared to 244 (24.4%) with low and 687 (68.7%) with extremely low levels of IgG antibodies to LF. Using overlapping decapeptide analysis, we identified six common LF antigenic regions targeted by those individuals with moderate levels of antibodies to LF and high in vitro toxin neutralizing activity. Affinity purified antibodies directed against antigenic epitopes within the PA binding and ADP-ribotransferase-like domains of LF were able to protect mice against lethal toxin challenge. Findings from these studies have important implications for vaccine design and immunotherapeutic development.

  6. Integrated MOSFET-Embedded-Cantilever-Based Biosensor Characteristic for Detection of Anthrax Simulant

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, Salwa [University of Tennessee, Knoxville (UTK); Lee, Ida [ORNL; Islam, Syed K [University of Tennessee, Knoxville (UTK); Eliza, Sazia A. [University of Tennessee, Knoxville (UTK); Shekhawat, Gajendra [Northwestern University, Evanston; Dravid, Vinayak [Northwestern University, Evanston; Tulip, Fahmida S [ORNL

    2011-01-01

    In this work, MOSFET-embedded cantilevers are configured as microbial sensors for detection of anthrax simulants, Bacillus thuringiensis. Anthrax simulants attached to the chemically treated gold-coated cantilever cause changes in the MOSFET drain current due to the bending of the cantilever which indicates the detection of anthrax simulant. Electrical properties of the anthrax simulant are also responsible for the change in the drain current. The test results suggest a detection range of 10 L of stimulant test solution (a suspension population of 1.3 107 colony-forming units/mL diluted in 40% ethanol and 60% deionized water) with a linear response of 31 A/ L.

  7. Clinical and epidemiological investigation of a fatal anthrax case in China.

    Science.gov (United States)

    Chen, Haiying; Bao, Wanguo; Wang, Yang; Zhang, Kaiyu; Wang, Feng

    2015-02-19

    Anthrax is a recessive infectious disease caused by the bacterium Bacillus anthracis, and is primarily a zoonotic disease. Until recently, Bacillus anthracis infections were relatively infrequent and confined to agrarian communities in underdeveloped countries. No anthrax cases were reported in Changchun City in the past few decades until a male patient from the Inner Mongolia Autonomous Region presented the anthrax disease manifestation. This paper describes an anthrax patient's diagnosis, isolation and treatment which involved institutions in two different Chinese provinces; the foci epidemiological investigation alongside with the outbreak management process, which is of great significance to control the spread of the recessive infection is also described.

  8. Development of a simple method for the rapid identification of organisms causing anthrax by coagglutination test.

    Science.gov (United States)

    Sumithra, T G; Chaturvedi, V K; Gupta, P K; Siju, S J; Susan, C; Bincy, J; Laxmi, U; Sunita, S C; Rai, A K

    2014-11-01

    A protective antigen (PA) based coagglutination test was optimized in the present study for the specific and sensitive identification of bacteria causing anthrax in a cost effective and less risky manner. The test showed 100% specificity and sensitivity up to 9 × 10(3) formalinized vegetative cells or 11 ng of PA. The optimized test also detected anthrax toxin directly from the serum as well as blood of anthrax infected animals indicating the potential application for direct diagnosis of anthrax under field conditions.

  9. Evaluation of the house fly Musca domestica as a mechanical vector for an anthrax.

    Directory of Open Access Journals (Sweden)

    Antonio Fasanella

    Full Text Available Anthrax is a disease of human beings and animals caused by the encapsulated, spore-forming, Bacillus anthracis. The potential role of insects in the spread of B. anthracis to humans and domestic animals during an anthrax outbreak has been confirmed by many studies. Among insect vectors, the house fly Musca domestica is considered a potential agent for disease transmission. In this study, laboratory-bred specimens of Musca domestica were infected by feeding on anthrax-infected rabbit carcass or anthrax contaminated blood, and the presence of anthrax spores in their spots (faeces and vomitus was microbiologically monitored. It was also evaluated if the anthrax spores were able to germinate and replicate in the gut content of insects. These results confirmed the role of insects in spreading anthrax infection. This role, although not major, given the huge size of fly populations often associated with anthrax epidemics in domestic animals, cannot be neglected from an epidemiological point of view and suggest that fly control should be considered as part of anthrax control programs.

  10. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  11. Cytoskeleton as an Emerging Target of Anthrax Toxins

    Directory of Open Access Journals (Sweden)

    Jean-Nicolas Tournier

    2012-02-01

    Full Text Available Bacillus anthracis, the agent of anthrax, has gained virulence through its exotoxins produced by vegetative bacilli and is composed of three components forming lethal toxin (LT and edema toxin (ET. So far, little is known about the effects of these toxins on the eukaryotic cytoskeleton. Here, we provide an overview on the general effects of toxin upon the cytoskeleton architecture. Thus, we shall discuss how anthrax toxins interact with their receptors and may disrupt the interface between extracellular matrix and the cytoskeleton. We then analyze what toxin molecular effects on cytoskeleton have been described, before discussing how the cytoskeleton may help the pathogen to corrupt general cell processes such as phagocytosis or vascular integrity.

  12. Economic Impacts of a Wide Area Release of Anthrax

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Olson, Jarrod; Stein, Steven L.; Lesperance, Ann M.

    2009-05-29

    This analysis explores economic impacts that might result from a wide-area release of anthrax. The intent is not to provide a quantitative analysis of such a disaster, but to: 1. Define the general categories of economic impacts that the region should be concerned about; and, 2. Explore what types of private sector businesses or industries, if any, may have the greatest impact on speeding the economic recovery of the region.

  13. Effective antiprotease-antibiotic treatment of experimental anthrax

    Directory of Open Access Journals (Sweden)

    MacAfee Rebecca

    2005-04-01

    Full Text Available Abstract Background Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. Methods Secreted proteins (other than lethal and edema toxins produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne spores. Results B. anthracis strain delta Ames (pXO1-, pXO2- producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline, as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. Conclusion Secreted proteolytic enzymes are important pathogenic

  14. Appropriation and commercialization of the Pasteur anthrax vaccine.

    Science.gov (United States)

    Cassier, Maurice

    2005-12-01

    Whereas Pasteur patented the biotechnological processes that he invented between 1857 and 1873 in the agro-food domain, he did not file any patents on the artificial vaccine preparation processes that he subsequently developed. This absence of patents can probably be explained by the 1844 patent law in France that established the non-patentable status of pharmaceutical preparations and remedies, including those for use in veterinary medicine. Despite the absence of patents, the commercial exploitation of the anthrax vaccine in the 1880s and 1890s led to a technical and commercial monopoly by Pasteur's laboratory as well as the founding of a commercial company to diffuse the vaccine abroad. Pasteur repeatedly refused to transfer his know-how and anthrax vaccine production methods to foreign laboratories, on the grounds that he wished to control the quality of the vaccines produced. Indeed, it was relatively difficult to transfer a method that was not yet perfectly stabilized in the early 1880s. Pasteur also wanted to maintain the monopoly of his commercial company and to increase the profits from vaccine sales so that the Institut Pasteur could be financially independent. The 'Pasteur anthrax vaccine' operating licences are described and analysed in detail in this article.

  15. Anthrax kills wild chimpanzees in a tropical rainforest.

    Science.gov (United States)

    Leendertz, Fabian H; Ellerbrok, Heinz; Boesch, Christophe; Couacy-Hymann, Emmanuel; Mätz-Rensing, Kerstin; Hakenbeck, Regine; Bergmann, Carina; Abaza, Pola; Junglen, Sandra; Moebius, Yasmin; Vigilant, Linda; Formenty, Pierre; Pauli, Georg

    2004-07-22

    Infectious disease has joined habitat loss and hunting as threats to the survival of the remaining wild populations of great apes. Nevertheless, relatively little is known about the causative agents. We investigated an unusually high number of sudden deaths observed over nine months in three communities of wild chimpanzees (Pan troglodytes verus) in the Taï National Park, Ivory Coast. Here we report combined pathological, cytological and molecular investigations that identified Bacillus anthracis as the cause of death for at least six individuals. We show that anthrax can be found in wild non-human primates living in a tropical rainforest, a habitat not previously known to harbour B. anthracis. Anthrax is an acute disease that infects ruminants, but other mammals, including humans, can be infected through contacting or inhaling high doses of spores or by consuming meat from infected animals. Respiratory and gastrointestinal anthrax are characterized by rapid onset, fever, septicaemia and a high fatality rate without early antibiotic treatment. Our results suggest that epidemic diseases represent substantial threats to wild ape populations, and through bushmeat consumption also pose a hazard to human health.

  16. Human Anthrax Transmission at the Urban-Rural Interface, Georgia.

    Science.gov (United States)

    Kracalik, Ian; Malania, Lile; Imnadze, Paata; Blackburn, Jason K

    2015-12-01

    Human anthrax has increased dramatically in Georgia and was recently linked to the sale of meat in an urban market. We assessed epidemiological trends and risk factors for human anthrax at the urban-rural interface. We reviewed epidemiologic records (2000-2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). To estimate risk, we used a negative binomial regression. The average incidence per 1 million population in peri-urban areas (24.5 cases) was > 2-fold higher compared with rural areas and > 3-fold higher compared with urban area. Risk from handling or purchasing meat was nearly 2-fold higher in urban areas and > 4-fold higher in peri-urban areas compared with rural area. Our findings suggest a high risk of anthrax in urban and peri-urban areas likely as a result of spillover from contaminated meat and animal by-products. Consumers should be warned to purchase meat only from licensed merchants.

  17. Interactions between Bacillus anthracis and plants may promote anthrax transmission.

    Directory of Open Access Journals (Sweden)

    Holly H Ganz

    2014-06-01

    Full Text Available Environmental reservoirs are essential in the maintenance and transmission of anthrax but are poorly characterized. The anthrax agent, Bacillus anthracis was long considered an obligate pathogen that is dormant and passively transmitted in the environment. However, a growing number of laboratory studies indicate that, like some of its close relatives, B. anthracis has some activity outside of its vertebrate hosts. Here we show in the field that B. anthracis has significant interactions with a grass that could promote anthrax spore transmission to grazing hosts. Using a local, virulent strain of B. anthracis, we performed a field experiment in an enclosure within a grassland savanna. We found that B. anthracis increased the rate of establishment of a native grass (Enneapogon desvauxii by 50% and that grass seeds exposed to blood reached heights that were 45% taller than controls. Further we detected significant effects of E. desvauxii, B. anthracis, and their interaction on soil bacterial taxa richness and community composition. We did not find any evidence for multiplication or increased longevity of B. anthracis in bulk soil associated with grass compared to controls. Instead interactions between B. anthracis and plants may result in increased host grazing and subsequently increased transmission to hosts.

  18. Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection.

    Science.gov (United States)

    Merkel, Tod J; Perera, Pin-Yu; Lee, Gloria M; Verma, Anita; Hiroi, Toyoko; Yokote, Hiroyuki; Waldmann, Thomas A; Perera, Liyanage P

    2013-09-01

    An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response.

  19. A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen

    Science.gov (United States)

    2014-08-01

    A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen...A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective Antigen...AND SUBTITLE A Chemically Synthesized Capture Agent Enables the Selective, Sensitive, and Robust Electrochemical Detection of Anthrax Protective

  20. 9 CFR 309.7 - Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livestock affected with anthrax... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways. (a) Any livestock found on ante-mortem inspection to be affected with anthrax shall be...

  1. 76 FR 34994 - Vaccine To Protect Children From Anthrax-Public Engagement Workshop

    Science.gov (United States)

    2011-06-15

    ... HUMAN SERVICES Vaccine To Protect Children From Anthrax--Public Engagement Workshop AGENCY: Office of... workshop on July 7, 2011, to discuss vaccine to protect children from anthrax. This meeting is open to the... vaccine to protect children would be to use an investigational new drug (IND) clinical protocol....

  2. Effect of Aluminum Hydroxide Adjuvant and Formaldehyde in the Formulation of rPA Anthrax Vaccine

    Science.gov (United States)

    2007-01-02

    dose, the recom- ended maximum concentration for anthrax vaccines based pon rPA is 500 g per dose. Our first experiment exam- ned the serological...anthrax. Infect Immun 2006;74:1016–24. 48] Herrmann JE, Wang S, Zhang C, Panchal RG, Bavari S, Lyons CR, et al. Passive immunotherapy of Bacillus anthracis

  3. Case Report of an Anthrax Presentation Relevant to Special Operations Medicine.

    Science.gov (United States)

    Winkler, Stephen; Enzenauer, Robert W; Karesh, James W; Pasteur, Nshimyimana; Eisnor, Derek L; Painter, Rex B; Calvano, Christopher J

    2016-01-01

    Special Operations Forces (SOF) medical personnel function worldwide in environments where endemic anthrax (caused by Bacillus anthracis infection) may present in one of three forms: cutaneous, pulmonary, or gastrointestinal. This report presents a rare periocular anthrax case from Haiti to emphasize the need for heightened diagnostic suspicion of unusual lesions likely to be encountered in SOF theaters.

  4. The pattern of anthrax cases on livestock in West Nusa Tenggara Province

    Directory of Open Access Journals (Sweden)

    Enymartindah

    1998-03-01

    Full Text Available A retrospective study on anthrax in endemic area was carried out from 1984 to 1994 in West Nusa Tenggara Province (NTB to uncover the occurrence of anthrax and the pattern of the disease in livestock. Data of anthrax incidence had been compiled for the 11 years from Animal Health Section and Type B Laboratory of the Livestock Service Office, NTB Province in Mataram. This was done to get the information about locations and times when the cases occurred, and the vaccination status of livestock in the anthrax area. The pattern of anthrax in livestock was analyzed by using time series analysis, and the long term trend was then illustrated by linier regression . During the years, anthrax cases in livestock were reported high in Sumbawa island, while the cases in Lombok island were relatively low. There were no anthrax cases reported from East Lombok District . The long term trend of anthrax occurrence in livestock from 1984 to 1994 tended to decrease (Y= 6,04 - 0,0162 X.

  5. Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst

    NARCIS (Netherlands)

    Guichard, Annabel; McGillivray, Shauna M.; Cruz-Moreno, Beatriz; van Sorge, Nina M.; Nizet, Victor; Bier, Ethan

    2010-01-01

    Bacillus anthracis is the causative agent of anthrax in humans and other mammals(1,2). In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mit

  6. Use of medical simulation to teach bioterrorism preparedness: the anthrax example.

    Science.gov (United States)

    Olsen, Martin E

    2013-01-01

    The 2001 anthrax bioterrorism attacks demonstrated vulnerability for future similar attacks. This article describes mechanisms that can be used to prepare the medical community and healthcare facilities for the diagnosis and management of a subsequent bioterrorism attack should such an event occur and the fundamentals of medical simulation and its use in teaching learners about the diagnosis of management of anthrax exposure.

  7. Awareness and attitude toward zoonoses with particular reference to anthrax among cattle owners in selected rural communities of Zimbabwe.

    Science.gov (United States)

    Chikerema, S M; Matope, G; Pfukenyi, D M

    2013-04-01

    We conducted a cross-sectional study to assess cattle owners' awareness, perceptions, and attitudes toward zoonoses, with particular emphasis regarding anthrax. Data on awareness of zoonoses, clinical signs of anthrax in animals and human, its routes of transmission and methods of prevention, the families' consumption habits of anthrax-infected carcasses, and other family activities that increase exposure to anthrax were collected using an interviewer-administered questionnaire. A total of 41.4% (135/326) of the farmers were from high-anthrax-risk districts, whereas 28.5% and 30.1% were from medium- and low-risk districts, respectively. Overall, the level of awareness amongst the farmers for the named zoonoses were rabies (88.7%), anthrax (71.5%), and brucellosis (20.9%). Except for anthrax, awareness of other zoonoses did not differ significantly (p>0.05) among the district categories. Farmers from anthrax high-risk districts were significantly more aware of anthrax compared to those from moderate- (p=0.000) and low- (p=0.000) risk districts. All of the farmers were aware that anthrax occurs in cattle, and 73% indicated the presence of unclotting blood oozing from natural orifices as a consistent finding in cattle that died of anthrax, whereas 86.7% of them indicated the presence of skin lesions as the most common sign of the disease in humans. The good efficacy of human anthrax treatment (58.3%), slaughter of moribund cattle and selling of meat from cattle found dead to unsuspecting consumers (59.8%), reluctance to lose animals (47.9%), and forgetting about anthrax (41.1%) were cited as the major reasons for consuming anthrax-infected carcasses. Given that 75.2% of cattle owners indicated that they would not consume meat from cattle found dead, because they were discouraged by veterinary authorities, introducing meat inspection services is likely to have a positive impact in preventing human anthrax outbreaks in Zimbabwe.

  8. Occupational mortality

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2011-01-01

    INTRODUCTION: This paper aims to present the methods and main results from the Danish occupational mortality studies, and to set the Danish studies into the international context of occupational mortality studies. RESEARCH TOPICS: The first Danish occupational mortality study from 1970...

  9. Keeping the Air Clean and Safe: An Anthrax Smoke Detector

    Science.gov (United States)

    2005-01-01

    Scientists at work in the Planetary Protection division at NASA s Jet Propulsion Laboratory (JPL) sterilize everything before blasting it to the Red Planet. They take great pains to ensure that all spacecraft are void of bacterial life, especially the microscopic bacteria that can live hundreds of years in their spore states. No one is quite sure what Earthly germs would do on Mars, but scientists agree that it is safest to keep the Martian terrain as undisturbed as possible. Errant Earth germs would also render useless the instruments placed on exploration rovers to look for signs of life, as the life that they registered would be life that came with them from Earth. A team at JPL, headed by Dr. Adrian Ponce, developed a bacterial spore-detection system that uses a simple and robust chemical reaction that visually alerts Planetary Protection crews. It is a simple air filter that traps micron-sized bacterial spores and then submits them to the chemical reaction. When the solution is then viewed under an ultraviolet light, the mixture will glow green if it is contaminated by bacteria. Scientists can then return to the scrubbing and cleaning stages of the sterilization process to remove these harmful bacteria. The detection system is the space-bound equivalent of having your hands checked for cleanliness before being allowed to the table; and although intended to keep terrestrial germs from space, this technology has awesome applications here on Mother Earth. The bacterial spore-detection unit can recognize anthrax and other harmful, spore-forming bacteria and alert people of the impending danger. As evidenced in the anthrax mailings of fall 2001 in the United States, the first sign of anthrax exposure was when people experienced flu-like symptoms, which unfortunately, can take as much as a week to develop after contamination. Anthrax cost 5 people their lives and infected 19 others; and the threat of bioterrorism became a routine concern, with new threats popping up

  10. Anthrax in a backyard domestic dog in Ukraine: a case report.

    Science.gov (United States)

    Blackburn, Jason K; Skrypnyk, Artem; Bagamian, Karoun H; Nikolich, Mikeljon P; Bezymennyi, Maksym; Skrypnyk, Valeriy

    2014-08-01

    Anthrax has been reported in domestic and wild dogs throughout much of the world. Generally, canids are considered resistant to anthrax, although there are several reports of anthrax deaths in both wild and domestic canid populations. Prior to 2012, anthrax had not been reported in dogs in Ukraine, despite a long history in livestock and wildlife. An outbreak involving at least one cow and one dog was reported from a backyard setting in southern Ukraine in August of 2012. Laboratory results and epizootic data were compiled from official investigation reports of regional and state veterinary services involved in the case response. A single dog died after being fed meat and bones from an illegally slaughtered heifer that died of anthrax 5 days earlier. On the evening of the dog's death, the dog refused food or water; however, there were no other clinical signs. Laboratory tests of dog tissue included traditional bacteriology for Bacillus anthracis, a small rodent bioassay for virulence, and immunoprecipitation tests (IPT). IPT was positive, viable B. anthracis colonies were cultured, and a bioassay confirmed virulence. This was the first confirmed case of canid anthrax in Ukraine. This case report serves to remind veterinary officials that anthrax can affect a wide number of species. We advise surveillance systems remain flexible and include animals that might not otherwise be tested.

  11. Military hospitalizations among deployed US service members following anthrax vaccination, 1998-2001.

    Science.gov (United States)

    Wells, Timothy Steven; Sato, Paul A; Smith, Tyler Clain; Wang, Linda Zhenling; Reed, Robert John; Ryan, Margaret Angela Kappel

    2006-01-01

    Safety concerns have confronted the Department of Defense Anthrax Vaccine Immunization Program since inception in 1998. To determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with Cox proportional hazards models. The study population consisted of 170,723 active duty US service members who were anthrax-vaccinated and deployed during the time period January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases diagnostic categories, autoimmune organ specific and organ non-specific hospitalizations, and asthma. After adjustment, anthrax vaccination was associated with significantly fewer hospitalizations for any-cause, diseases of the blood and blood forming organs, and diseases of the respiratory system. Comparing anthrax post-vaccination hospitalization experience with the pre-vaccination period resulted in no significant increased hazard for any of the hospitalization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax vaccine and deployment on health outcomes among US service members needs further study.

  12. Risk practices for animal and human anthrax in Bangladesh: an exploratory study

    Science.gov (United States)

    Islam, Md. Saiful; Hossain, M. Jahangir; Mikolon, Andrea; Parveen, Shahana; Khan, M. Salah Uddin; Haider, Najmul; Chakraborty, Apurba; Titu, Abu Mohammad Naser; Rahman, M. Waliur; Sazzad, Hossain M. S.; Rahman, Mahmudur; Gurley, Emily S.; Luby, Stephen P.

    2013-01-01

    Introduction From August 2009 to October 2010, International Centre for Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease Control and Research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program. Methods Field anthropologists used qualitative data-collection tools, including 15 hours of unstructured observations, 11 key informant interviews, 32 open-ended interviews, and 6 group discussions in 5 anthrax-affected villages. Results Each cattle owner in the affected communities raised a median of six ruminants on their household premises. The ruminants were often grazed in pastures and fed supplementary rice straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake; lactating cows were given dicalcium phosphate. Cattle represented a major financial investment. Since Islamic law forbids eating animals that die from natural causes, when anthrax-infected cattle were moribund, farmers often slaughtered them on the household premises while they were still alive so that the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners removed and sold the hides from discarded carcasses. Farmers discarded the carcasses and slaughtering waste into ditches, bodies of water, or open fields. Cattle in the affected communities did not receive routine anthrax vaccine due to low production, poor distribution, and limited staffing for vaccination. Conclusion Slaughtering anthrax-infected animals and disposing of butchering waste and carcasses in environments where ruminants live and graze, combined with limited vaccination, provided a context that permitted repeated anthrax outbreaks in animals and humans. Because of strong financial incentives

  13. Risk practices for animal and human anthrax in Bangladesh: an exploratory study

    Directory of Open Access Journals (Sweden)

    Md. Saiful Islam

    2013-11-01

    Full Text Available Introduction: From August 2009 to October 2010, International Centre for Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease Control and Research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program. Methods: Field anthropologists used qualitative data-collection tools, including 15 hours of unstructured observations, 11 key informant interviews, 32 open-ended interviews, and 6 group discussions in 5 anthrax-affected villages. Results: Each cattle owner in the affected communities raised a median of six ruminants on their household premises. The ruminants were often grazed in pastures and fed supplementary rice straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake; lactating cows were given dicalcium phosphate. Cattle represented a major financial investment. Since Islamic law forbids eating animals that die from natural causes, when anthrax-infected cattle were moribund, farmers often slaughtered them on the household premises while they were still alive so that the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners removed and sold the hides from discarded carcasses. Farmers discarded the carcasses and slaughtering waste into ditches, bodies of water, or open fields. Cattle in the affected communities did not receive routine anthrax vaccine due to low production, poor distribution, and limited staffing for vaccination. Conclusion: Slaughtering anthrax-infected animals and disposing of butchering waste and carcasses in environments where ruminants live and graze, combined with limited vaccination, provided a context that permitted repeated anthrax outbreaks in animals and humans. Because of strong

  14. Detection of anthrax toxin genetic sequences by the solid phase oligo-probes

    Directory of Open Access Journals (Sweden)

    K C Addanki

    2011-01-01

    Full Text Available Purpose: There is an urgent need to detect a rapid field-based test to detect anthrax. We have developed a rapid, highly sensitive DNA-based method to detect the anthrax toxin lethal factor gene located in pXO1, which is necessary for the pathogenicity of Bacillus anthracis. Materials and Methods: We have adopted the enzyme-linked immunosorbent assay (ELISA so that instead of capturing antibodies we capture the DNA of the target sequence by a rapid oligo-based hybridization and then detect the captured DNA with another oligoprobe that binds to a different motif of the captured DNA sequences at a dissimilar location. We chose anthrax lethal factor endopeptidase sequences located in pXO1 and used complementary oligoprobe, conjugated with biotin, to detect the captured anthrax specific sequence by the streptavidin-peroxidase-based colorimetric assay. Result: Our system can detect picomoles (pMoles of anthrax (approximately 33 spores of anthrax and is >1000 times more sensitive than the current ELISA, which has a detection range of 0.1 to 1.0 ng/mL. False positive results can be minimized when various parameters and the colour development steps are optimized. Conclusion: Our results suggest that this assay can be adapted for the rapid detection of minuscule amounts of the anthrax spores that are aerosolized in the case of a bioterrorism attack. This detection system does not require polymerase chain reaction (PCR step and can be more specific than the antibody method. This method can also detect genetically engineered anthrax. Since, the antibody method is so specific to the protein epitope that bioengineered versions of anthrax may not be detected.

  15. [Characteristics of anthrax: its description and biblical name--Shehin].

    Science.gov (United States)

    Ben-Noun, Liubov

    2002-05-01

    The illness known as Anthrax is very rare in the west. In developing countries relatively significant numbers of cases are found, particularly in animals. However, biological terrorist acts could cause it to spread. In Hebrew, the illness is now called Gahelet or Gameret. The purpose of this paper is to examine whether the illness is described in the Bible, and if so, to present that description and provide a broader survey of the features of this illness. The word Gahelet appears in the Bible, but not indicating a disease, while the source of Gameret is in the Talmud. In the Bible, Shehin is mentioned as the sixth of the ten plagues in Egypt, and also as the disease that affected Job. The natural course of the condition, as described in the Bible, matches the clinical symptoms of Anthrax, as we know it today. The Hebrew Language Academy is therefore advised to adopt the findings of this paper, and confirm the name of the illness in Israel--Shehin.

  16. Epidemiology of Human Anthrax in China, 1955−2014

    Science.gov (United States)

    Li, Yu; Yin, Wenwu; Hugh-Jones, Martin; Wang, Liping; Mu, Di; Ren, Xiang; Zeng, Lingjia; Chen, Qiulan; Li, Wei; Wei, Jianchun; Lai, Shengjie; Zhou, Hang

    2017-01-01

    Using national surveillance data for 120,111 human anthrax cases recorded during 1955−2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005−2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax. PMID:27983489

  17. Suppressive effects of anthrax lethal toxin on megakaryopoiesis.

    Directory of Open Access Journals (Sweden)

    Po-Kong Chen

    Full Text Available Anthrax lethal toxin (LT is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogen-activated protein kinases (MAPKs, which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34(+ cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

  18. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

    Directory of Open Access Journals (Sweden)

    Paul Keim

    2015-11-01

    Lay Person Interpretation: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a >12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.

  19. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    OpenAIRE

    Popov, Serguei G.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles

    2011-01-01

    AIM: To establish whether activation of adenosine type-3 receptors (A3Rs) and inhibition of interleukin-1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores.

  20. Anthrax in injecting drug users: the need for increased vigilance in the clinic.

    Science.gov (United States)

    Ascough, Stephanie; Altmann, Daniel Martin

    2015-06-01

    The emergence of a previously unrecognized route of Bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern Europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. With a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. Lack of awareness of this syndrome among emergency room clinicians can lead to a delayed diagnosis among heroin users; indeed, for many health workers in developed countries, where infection by B. anthracis is rare, this may be the first time they have encountered anthrax infections. As the putative route of contamination of the heroin supply is potentially ongoing, it is important that clinicians and public health workers remain vigilant for early signs of injectional anthrax.

  1. Enhancement of the Anthrax AVA Vaccine with CpG ODN’s

    Science.gov (United States)

    2005-08-28

    NUMBER OF PAGES 20. LIMITATION OF ABSTRACT UL - 28-Aug-2005 Final Report on ACCELERATE ANTHRAX: CpG 7909 Vaccine Adjuvant Program Report Title...Vaccine Adsorbed (BioThrax?) Combined with CPG 7909 in Normal Volunteers” was completed and presented at the 2005 Interscience Conference on Antimicrobial...Agents and Chemotherapy in a poster entitled “Marked Enhancement Of Antibody Response To Anthrax Vaccine Adsorbed With CPG 7909 In Healthy

  2. Anthrax, Toxins and Vaccines: A 125-Year Journey Targeting Bacillus anthracis

    Science.gov (United States)

    2009-01-01

    after their inception. Since these early begin- nings, additional medical history linked to B. anthracis coincides in many ways with vac- cines that...by vaccination. Hopefully, the reader will be challenged to think of how existing anthrax vaccines, especially those meant for humans, can be...improved with available knowledge/technology. The many current anthrax vaccines are linked to Louis Pasteur’s seminal experiments at Pouilly Ie-Fort in

  3. Lessons for control of heroin-associated anthrax in Europe from 2009-2010 outbreak case studies, London, UK.

    Science.gov (United States)

    Abbara, Aula; Brooks, Tim; Taylor, Graham P; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel; Holmes, Alison

    2014-07-01

    Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community.

  4. Animal models of human anthrax: the Quest for the Holy Grail.

    Science.gov (United States)

    Goossens, Pierre L

    2009-12-01

    Anthrax is rare among humans, few data can be collected from infected individuals and they provide a fragmentary view of the dynamics of infection and human host-pathogen interactions. Therefore, the development of animal models is necessary. Anthrax has the particularity of being a toxi-infection, a combination of infection and toxemia. The ideal animal model would explore these two different facets and mimic human disease as much as possible. In the past decades, the main effort has been focused on modelling of inhalational anthrax and the perception of specific aspects of the infection has evolved in recent years. In this review, we consider criteria which can lead to the most appropriate choice of a given animal species for modelling human anthrax. We will highlight the positive input and limitations of different models and show that they are not mutually exclusive. On the contrary, their contribution to anthrax research can be more rewarding when taken in synergy. We will also present a reappraisal of inhalational anthrax and propose reflections on key points, such as portal of entry, connections between mediastinal lymph nodes, pleura and lymphatic drainage.

  5. Investigation of Anthrax Cases in North-East China, 2010-2014.

    Science.gov (United States)

    Zhou, Wei; Sun, Yang; Zhu, Lingwei; Zhou, Bo; Liu, Jun; Ji, Xue; Wang, Xiaofeng; Wang, Nan; Gu, Guibo; Feng, Shuzhang; Qian, Jun; Guo, Xuejun

    2015-01-01

    We determined the genotypes of seven Bacillus anthracis strains that were recovered from nine anthrax outbreaks in North-East China from 2010 to 2014, and two approved vaccine strains that are currently in use in China. The causes of these cases were partly due to local farmers being unaware of the presence of anthrax, and butchers with open wounds having direct contact with anthrax-contaminated meat products. The genotype of five of the seven recovered strains was A.Br.001/002 sub-lineage, which was concordant with previously published research. The remaining two cases belongs to the A.Br.Ames sub-lineage. Both of these strains displayed an identical SNR pattern, which was the first time that this genotype was identified in North-East China. Strengthening education in remote villages of rural China is an important activity aimed at fostering attempts to prevent and control anthrax. The genotype of the vaccine strain Anthrax Spore Vaccine No.II was A.Br.008/009 and A.Br.001/002 for the vaccine strain Anthrax Spore Vaccine Non-capsulated. Further studies of their characteristics are clearly warranted.

  6. Prediction of Protein-Peptide Interactions: Application of the XPairIT to Anthrax Lethal Factor and Substrates

    Science.gov (United States)

    2013-09-01

    Prediction of Protein-Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates by Margaret M. Hurley and...Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates Margaret M. Hurley and Michael S. Sellers Weapons and...Prediction of Protein-Peptide Interactions: Application of the XPairIt API to Anthrax Lethal Factor and Substrates 5a. CONTRACT NUMBER ORAUW911QX-04-C

  7. In silico design of smart binders to anthrax PA

    Science.gov (United States)

    Sellers, Michael; Hurley, Margaret M.

    2012-06-01

    The development of smart peptide binders requires an understanding of the fundamental mechanisms of recognition which has remained an elusive grail of the research community for decades. Recent advances in automated discovery and synthetic library science provide a wealth of information to probe fundamental details of binding and facilitate the development of improved models for a priori prediction of affinity and specificity. Here we present the modeling portion of an iterative experimental/computational study to produce high affinity peptide binders to the Protective Antigen (PA) of Bacillus anthracis. The result is a general usage, HPC-oriented, python-based toolkit based upon powerful third-party freeware, which is designed to provide a better understanding of peptide-protein interactions and ultimately predict and measure new smart peptide binder candidates. We present an improved simulation protocol with flexible peptide docking to the Anthrax Protective Antigen, reported within the context of experimental data presented in a companion work.

  8. Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R.

    Science.gov (United States)

    Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-02-25

    Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2-) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R.

  9. Monitoring Method of Cow Anthrax Based on Gis and Spatial Statistical Analysis

    Science.gov (United States)

    Li, Lin; Yang, Yong; Wang, Hongbin; Dong, Jing; Zhao, Yujun; He, Jianbin; Fan, Honggang

    Geographic information system (GIS) is a computer application system, which possesses the ability of manipulating spatial information and has been used in many fields related with the spatial information management. Many methods and models have been established for analyzing animal diseases distribution models and temporal-spatial transmission models. Great benefits have been gained from the application of GIS in animal disease epidemiology. GIS is now a very important tool in animal disease epidemiological research. Spatial analysis function of GIS can be widened and strengthened by using spatial statistical analysis, allowing for the deeper exploration, analysis, manipulation and interpretation of spatial pattern and spatial correlation of the animal disease. In this paper, we analyzed the cow anthrax spatial distribution characteristics in the target district A (due to the secret of epidemic data we call it district A) based on the established GIS of the cow anthrax in this district in combination of spatial statistical analysis and GIS. The Cow anthrax is biogeochemical disease, and its geographical distribution is related closely to the environmental factors of habitats and has some spatial characteristics, and therefore the correct analysis of the spatial distribution of anthrax cow for monitoring and the prevention and control of anthrax has a very important role. However, the application of classic statistical methods in some areas is very difficult because of the pastoral nomadic context. The high mobility of livestock and the lack of enough suitable sampling for the some of the difficulties in monitoring currently make it nearly impossible to apply rigorous random sampling methods. It is thus necessary to develop an alternative sampling method, which could overcome the lack of sampling and meet the requirements for randomness. The GIS computer application software ArcGIS9.1 was used to overcome the lack of data of sampling sites.Using ArcGIS 9.1 and GEODA

  10. The evaluation of clinical and laboratory findings of 63 inpatient with cutaneous anthrax: Characteristics of cutaneous anthrax in Turkey

    Directory of Open Access Journals (Sweden)

    Hatice Uce Özkol

    2014-12-01

    Full Text Available Background and Design: Despite a very uncommon disease in developed countries, cutaneous anthrax (CA is currently endemic in our countries. In this study, we aimed to bring out characteristic of anthrax of Turkey by comparing our results and the other CA reports in Turkey. Materials and Methods: Sixty three inpatients with CA between October 2009 and December 2012 were investigated retrospectively. All patients were diagnosed CA by clinical finding and/or microbiological examination. The demographic characteristics patient, routine tests, wound culture and gram staining results were recorded. Results were recorded on statistical program of SPSS 13.0 and were written using percent (%. Results: There were 63 inpatients (41 female (65.1%, 22 male (34.9%, mean age 35.9 years range10-83. Forty nine patients (77.8% had a history of contact with animals or animal product. Thirty-eight (60.3% and twenty-one (33.3% patients were found in the summer and fall season, respectively. Gram staining and culture were performed in 51 patients. Gram-positive bacilli were detected in 17 patients (33.3% by gram smear. Bacillus anthracis bacilli were produced in 11 patients (21.5% in cultures test. The lesions were mostly seen on the left hand (30.2%. Penicillin was most frequently preferred in treatment of CA (87.3%. Conclusion: CA is still endemic in Eastern Anatolia and continues to increase in recent years. Women living in the villages in which income is obtained from buying and selling of animals constitute the most important risk group. Preventive actions such as training of the risky society, vaccination of animals, and obstructing of illegal animal entries across the border, will reduce the incidence of CA.

  11. A One Health, participatory epidemiology assessment of anthrax (Bacillus anthracis) management in Western Uganda.

    Science.gov (United States)

    Coffin, Jeanne L; Monje, Fred; Asiimwe-Karimu, Grace; Amuguni, Hellen Janetrix; Odoch, Terence

    2015-03-01

    Sporadic anthrax outbreaks have occurred in and around Uganda's Queen Elizabeth National Park (QENP) for years, affecting wildlife, domestic animals, and humans. Reported outbreaks (2004-2005 and 2010) in QENP collectively killed over 500 wild animals and over 400 domestic animals. A 2011 outbreak in Sheema district temporarily froze local markets while killing two humans and seven bovines. One Health is multidisciplinary at its core, yet studies sometimes focus on the effects of animals on human health to the detriment of investigating the surrounding ecological and cultural contexts. Participatory methods connect problems - such as disease - to their context. A multidisciplinary team used participatory epidemiology and conventional structured questionnaires to investigate the impacts of anthrax on human livelihoods and the related perceptions of conservation, public health, and veterinary health efforts in the QENP area. Proximities to previous anthrax outbreaks and to QENP were treated as risk factors in the collection and evaluation of data. Participants' feedback indicates that anthrax prevalence may be greater than officially reported. Community member perceptions about anthrax and other diseases appear to be more closely related to their proximity to QENP than their proximity to anthrax outbreaks. Neither risk factor had a strong effect on knowledge of disease, nor any effect on behaviors associated with disease response or control. Instead, participants reported that social pressures, the economics of poverty, and the lack of health and veterinary infrastructure highly influenced responses to disease. The complex connections between the social needs and the economic context of these communities seem to be undermining current anthrax control and education measures. This livelihood-based decision-making may be unlikely to respond to educational intervention alone. This study provides a strong base for further research and for improvements in effective disease

  12. 1958-2010年阿坝州炭疽流行状况分析%Prevalence of Anthrax in Aba Prefecture, 1958 -2010

    Institute of Scientific and Technical Information of China (English)

    敬琼

    2012-01-01

    目的 分析阿坝州1958 -2010年炭疽发病情况,找出发病规律和特点,探讨有效降低炭疽病发病的措施和方法.方法 对53年来的炭疽疫情数据进行流行病学分析.结果 53年来累计报告炭疽病例1 349例,死亡21例,年均发病率3.47/10万、死亡率0.06/10万.全年均有病例报告,但集中在4~10月,3个牧区县的发病占报告总数的89.03%;职业以牧民为主,发病年龄集中在20~44岁.1958 - 2001年发病率在0.8/10万~2.52/10万之间,2002-2010年发病率在6.33/10万~12.66/10万之间.结论 阿坝州1958 -2001年炭疽发病较平稳,2002年起发病呈逐年上升趋势,且发病主要在牧区,应加强健康教育和畜牧业管理,做好疫点、外环境消毒和预防接种,有效控制牧区炭疽流行.%Objective By analyzing the incidence of anthrax in Aba prefecture from year 1958 to 2010, to find out the rules and features of the incidence, and explore effective measures to reduce the incidence of anthrax. Methods Data of anthrax epidemics in 53 years (1958 -2010) was analyzed with epidemiological methods. Results Totally 1 349 anthrax cases were reported in 53 years, with 21 death cases. The annual incidence rate was 3.47/105, and case mortality rate was 0. 06/105. Cases were reported throughout the year, and concentrated in period of April to October, 89. 03% cases were from 3 pastoral counties. Professional was mainly pas-toralists, and cases concentrated in 20 -44 years old. Annual incidence rate during 1958 -2001 fluctuated within 0. 8/105 -2. 52/105, and annual incidence rate was from 6. 33/105 to 12. 66/105 during 2002 -2010. Conclusions The incidence of anthrax was stable in Aba prefecture during 1958 - 2001, followed by the in- , creasing since 2002 year by year, and mainly in pastoral areas. Health education and animal husbandry management should be strengthened, with epidemic focus and external environment disinfection and vaccination, to control the prevalence of

  13. Mortality investigation

    Science.gov (United States)

    Work, Thierry M.; Franson, J. Christian; Friend, Milton; Gibbs, Samantha E.J.; Wild, Margaret A.

    2015-01-01

    Wildlife mortality events usually occur unannounced and may find management agencies unaware. These events can become highly visible and politically charged affairs, depending upon the scale or species involved. The public, media, and (or) politicians may pressure managers, field investigators, and diagnosticians to quickly identify the cause or to comment on potential causes, the significance of the event, what is being done about it, and a resolution. It may be common during such events for speculation to rage, and for conflicting theories to be advanced to explain either the environmental conditions that led to the mortality or the actual cause of death.

  14. 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

  15. Evidence of local persistence of human anthrax in the country of georgia associated with environmental and anthropogenic factors.

    Directory of Open Access Journals (Sweden)

    Ian T Kracalik

    Full Text Available BACKGROUND: Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters. METHODS/FINDINGS: A database of human cutaneous anthrax in Georgia during the period 2000-2009 was constructed using a geographic information system (GIS with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas. CONCLUSIONS/SIGNIFICANCE: Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns.

  16. Evidence of Local Persistence of Human Anthrax in the Country of Georgia Associated with Environmental and Anthropogenic Factors

    Science.gov (United States)

    Kracalik, Ian T.; Malania, Lile; Tsertsvadze, Nikoloz; Manvelyan, Julietta; Bakanidze, Lela; Imnadze, Paata; Tsanava, Shota; Blackburn, Jason K.

    2013-01-01

    Background Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters. Methods/Findings A database of human cutaneous anthrax in Georgia during the period 2000–2009 was constructed using a geographic information system (GIS) with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas. Conclusions/Significance Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns. PMID:24040426

  17. Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

    Directory of Open Access Journals (Sweden)

    Chenguang Cai

    Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

  18. 9 CFR 310.9 - Anthrax; carcasses not to be eviscerated; disposition of affected carcasses; hides, hoofs, horns...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anthrax; carcasses not to be...-MORTEM INSPECTION § 310.9 Anthrax; carcasses not to be eviscerated; disposition of affected carcasses...; general cleanup and disinfection. (a) Carcasses found before evisceration to be affected with...

  19. Genome Sequence of Historical Bacillus anthracis Strain Tyrol 4675 Isolated from a Bovine Anthrax Case in Austria

    Science.gov (United States)

    Antwerpen, Markus; Wölfel, Roman

    2017-01-01

    ABSTRACT In 1988, an outbreak of anthrax occurred among cattle in the Austrian state of Tyrol. Since then, Austria has been declared anthrax-free. Here, we report the draft genome sequence of one of these last outbreak strains, Bacillus anthracis Tyrol 4675, isolated from a diseased cow. PMID:28280006

  20. Lethal factor and anti-protective antigen IgG levels associated with inhalation anthrax, Minnesota, USA.

    Science.gov (United States)

    Sprenkle, Mark D; Griffith, Jayne; Marinelli, William; Boyer, Anne E; Quinn, Conrad P; Pesik, Nicki T; Hoffmaster, Alex; Keenan, Joseph; Juni, Billie A; Blaney, David D

    2014-02-01

    Bacillus anthracis was identified in a 61-year-old man hospitalized in Minnesota, USA. Cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen. Treatment comprising antimicrobial drugs, anthrax immune globulin, and pleural drainage led to full recovery; however, the role of passive immunization in anthrax treatment requires further evaluation.

  1. Antidotes to anthrax lethal factor intoxication. Part 1: Discovery of potent lethal factor inhibitors with in vivo efficacy.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2010-11-15

    Sub-nanomolar small molecule inhibitors of anthrax lethal factor have been identified using SAR and Merck L915 (4) as a model compound. One of these compounds (16) provided 100% protection in a rat lethal toxin model of anthrax disease.

  2. Antibacterial Properties of Visible-Light-Responsive Carbon-Containing Titanium Dioxide Photocatalytic Nanoparticles against Anthrax

    Directory of Open Access Journals (Sweden)

    Der-Shan Sun

    2016-12-01

    Full Text Available The bactericidal activity of conventional titanium dioxide (TiO2 photocatalyst is effective only on irradiation by ultraviolet light, which restricts the applications of TiO2 for use in living environments. Recently, carbon-containing TiO2 nanoparticles [TiO2(C NP] were found to be a visible-light-responsive photocatalyst (VLRP, which displayed significantly enhanced antibacterial properties under visible light illumination. However, whether TiO2(C NPs exert antibacterial properties against Bacillus anthracis remains elusive. Here, we evaluated these VLRP NPs in the reduction of anthrax-induced pathogenesis. Bacteria-killing experiments indicated that a significantly higher proportion (40%–60% of all tested Bacillus species, including B. subtilis, B. cereus, B. thuringiensis, and B. anthracis, were considerably eliminated by TiO2(C NPs. Toxin inactivation analysis further suggested that the TiO2(C NPs efficiently detoxify approximately 90% of tested anthrax lethal toxin, a major virulence factor of anthrax. Notably, macrophage clearance experiments further suggested that, even under suboptimal conditions without considerable bacterial killing, the TiO2(C NP-mediated photocatalysis still exhibited antibacterial properties through the reduction of bacterial resistance against macrophage killing. Our results collectively suggested that TiO2(C NP is a conceptually feasible anti-anthrax material, and the relevant technologies described herein may be useful in the development of new strategies against anthrax.

  3. Anthrax toxin receptor 2a controls mitotic spindle positioning.

    Science.gov (United States)

    Castanon, I; Abrami, L; Holtzer, L; Heisenberg, C P; van der Goot, F G; González-Gaitán, M

    2013-01-01

    Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.

  4. Anthrax Sampling and Decontamination: Technology Trade-Offs

    Energy Technology Data Exchange (ETDEWEB)

    Price, Phillip N.; Hamachi, Kristina; McWilliams, Jennifer; Sohn, Michael D.

    2008-09-12

    The goal of this project was to answer the following questions concerning response to a future anthrax release (or suspected release) in a building: 1. Based on past experience, what rules of thumb can be determined concerning: (a) the amount of sampling that may be needed to determine the extent of contamination within a given building; (b) what portions of a building should be sampled; (c) the cost per square foot to decontaminate a given type of building using a given method; (d) the time required to prepare for, and perform, decontamination; (e) the effectiveness of a given decontamination method in a given type of building? 2. Based on past experience, what resources will be spent on evaluating the extent of contamination, performing decontamination, and assessing the effectiveness of the decontamination in abuilding of a given type and size? 3. What are the trade-offs between cost, time, and effectiveness for the various sampling plans, sampling methods, and decontamination methods that have been used in the past?

  5. Mortality Implications of Mortality Plateaus

    DEFF Research Database (Denmark)

    Missov, T. I.; Vaupel, J. W.

    2015-01-01

    This article aims to describe in a unified framework all plateau-generating random effects models in terms of (i) plausible distributions for the hazard (baseline mortality) and the random effect (unobserved heterogeneity, frailty) as well as (ii) the impact of frailty on the baseline hazard. Mor...

  6. Pathogenic ecology: Where have all the pathogens gone? Anthrax: a classic case

    Science.gov (United States)

    Kiel, Johnathan; Walker, Wes W.; Andrews, Carrie J.; De Los Santos, Amy; Adams, Roy N.; Bucholz, Matthew W.; McBurnett, Shelly D.; Fuentes, Vladimir; Rizner, Karon E.; Blount, Keith W.

    2009-05-01

    Pathogenic ecology is the natural relationship to animate and inanimate components of the environment that support the sustainment of a pathogen in the environment or prohibit its sustainment, or their interactions with an introduced pathogen that allow for the establishment of disease in a new environment. The anthrax bacterium in the spore form has been recognized as a highly likely biological warfare or terrorist agent. The purpose of this work was to determine the environmental reservoir of Bacillus anthracis between outbreaks of anthrax and to examine the potential factors influencing the conversion of the Bacillus anthracis from a quiescent state to the disease causing state. Here we provide environmental and laboratory data for the cycling of Bacillus anthracis in plants to reconcile observations that contradict the soil borne hypothesis of anthrax maintenance in the environment.

  7. Naturally acquired anthrax antibodies in a cheetah (Acinonyx jubatus) in Botswana.

    Science.gov (United States)

    Good, Kyle M; Houser, Annmarie; Arntzen, Lorraine; Turnbull, Peter C B

    2008-07-01

    An outbreak of anthrax in the Jwana Game Reserve in Jwaneng, Botswana, was first observed when three cheetahs (Acinonyx jubatus) died of the disease in November 2004. In the aftermath of this event, banked serum samples collected from 23 wild-caught cheetahs were examined, by the inhibition enzyme-linked immunoassay (ELISA), for antibodies to the protective antigen (PA) of Bacillus anthracis. Of the 23 cheetahs, 16 regularly accessed the reserve. Antibodies to PA were detected in one cheetah collected in May 2004, indicating the disease was occurring well before it was first noticed. This appears to be the first demonstration of naturally acquired anthrax antibodies in cheetahs. The finding of one antibody-positive animal amongst at least 16 potentially exposed individuals is consistent with existing reports that it is uncommon for cheetahs to develop natural immunity to anthrax.

  8. Human Cutaneous Anthrax, the East Anatolian Region of Turkey 2008-2014.

    Science.gov (United States)

    Parlak, Emine; Parlak, Mehmet

    2016-01-01

    Anthrax is a zoonotic infectious disease caused by Bacillus anthracis. While anthrax is rare in developed countries, it is endemic in Turkey. The names of the different forms of the disease refer to the manner of entry of the spores into the body-cutaneous, gastrointestinal, inhalation, and injection. The purpose of this study was to evaluate the clinical characteristics, epidemiological history, treatment, and outcomes of patients with anthrax. Eighty-two cases of anthrax hospitalized at Atatürk University Faculty of Medicine Department of Infectious Diseases and Clinical Microbiology in 2008-2014 were examined retrospectively. Gender, age, occupation, year, history, clinical characteristics, character of lesions, length of hospitalization, and outcomes were recorded. Thirty (36.6%) patients were female and 52 (63.4%) patients were male; ages were 18-69 and mean age was 43.77 ± 13.05. The mean incubation period was 4.79 ± 3.76 days. Cases were largely identified in August (41.5%) and September (25.6%). Sixty-nine (84.1%) of the 82 patients had been given antibiotics before presentation. Lesions were most common on the fingers and arms. The most common occupational groups were housewives (36.6%) and people working in animal husbandry (31.7%). All patients had histories of contact with diseased animals and animal products. Penicillin-group antibiotics (78%) were most commonly used in treatment. One patient (1.2%) died from anthrax meningitis. The mean length of hospitalization was 8.30 ± 5.36 days. Anthrax is an endemic disease of economic and social significance for the region. Effective public health control measures, risk group education, vaccination of animals, and decontamination procedures will reduce the number of cases.

  9. Certhrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus.

    Science.gov (United States)

    Visschedyk, Danielle; Rochon, Amanda; Tempel, Wolfram; Dimov, Svetoslav; Park, Hee-Won; Merrill, A Rod

    2012-11-30

    We identified Certhrax, the first anthrax-like mART toxin from the pathogenic G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with anthrax lethal factor from Bacillus anthracis; however, we have shown that the toxicity of Certhrax resides in the mART domain, whereas anthrax uses a metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to require protective antigen for host cell entry. This two-domain enzyme was shown to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax localizes to distinct regions within mouse RAW264.7 cells by 10 min postinfection and is extranuclear in its cellular location. Substitution of catalytic residues shows that the mART function is responsible for the toxicity, and it binds NAD(+) with high affinity (K(D) = 52.3 ± 12.2 μM). We report the 2.2 Å Certhrax structure, highlighting its structural similarities and differences with anthrax lethal factor. We also determined the crystal structures of two good inhibitors (P6 (K(D) = 1.7 ± 0.2 μM, K(i) = 1.8 ± 0.4 μM) and PJ34 (K(D) = 5.8 ± 2.6 μM, K(i) = 9.6 ± 0.3 μM)) in complex with Certhrax. As with other toxins in this family, the phosphate-nicotinamide loop moves toward the NAD(+) binding site with bound inhibitor. These results indicate that Certhrax may be important in the pathogenesis of B. cereus.

  10. Redefining the Australian Anthrax Belt: Modeling the Ecological Niche and Predicting the Geographic Distribution of Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Alassane S Barro

    2016-06-01

    Full Text Available The ecology and distribution of B. anthracis in Australia is not well understood, despite the continued occurrence of anthrax outbreaks in the eastern states of the country. Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extending from southeast Queensland through the centre of New South Wales and into northern Victoria. This definition of the anthrax belt does not consider the role of environmental conditions in the distribution of B. anthracis. Here, we used the genetic algorithm for rule-set prediction model system (GARP, historical anthrax outbreaks and environmental data to model the ecological niche of B. anthracis and predict its potential geographic distribution in Australia. Our models reveal the niche of B. anthracis in Australia is characterized by a narrow range of ecological conditions concentrated in two disjunct corridors. The most dominant corridor, used to redefine a new anthrax belt, parallels the Eastern Highlands and runs from north Victoria to central east Queensland through the centre of New South Wales. This study has redefined the anthrax belt in eastern Australia and provides insights about the ecological factors that limit the distribution of B. anthracis at the continental scale for Australia. The geographic distributions identified can help inform anthrax surveillance strategies by public and veterinary health agencies.

  11. Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.

    Directory of Open Access Journals (Sweden)

    Srinivas Kammanadiminti

    Full Text Available BACKGROUND: We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. METHODS: Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30-96 hours after anthrax exposure. RESULTS: The majority of treated animals (>88% survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. CONCLUSIONS: The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

  12. Mortal assets

    Energy Technology Data Exchange (ETDEWEB)

    Howe, Geoffrey R.; Zablotska, Lydia B.; Fix, John J.; Egel, John N.; Buchanan, Jeffrey A.

    2005-11-01

    Workers employed in 15 utilities that generate nuclear power in the United States have been followed for up to 18 years between 1979 and 1997. Their cumulative dose from whole-body ionizing radiation has been determined from the dose records maintained by the facilities themselves and the REIRS and REMS systems maintained by the Nuclear Regulatory Commission and the Department of Energy, respectively. Mortality in the cohort from a number of causes has been analyzed with respect to individual radiation doses. The cohort displays a very substantial healthy worker effect, i.e. considerably lower cancer and noncancer mortality than the general population. Based on 26 and 368 deaths, respectively, positive though statistically nonsignificant associations were seen for mortality from leukemia (excluding chronic lymphocytic leukemia) and all solid cancers combined, with excess relative risks per sievert of 5.67 (95% confidence interval (CI) -2.56, 30.4) and 0.596 (95% CI -2.01, 4.64), respectively. These estimates are very similar to those from the atomic bomb survivors study, though the wide confidence intervals are also consistent with lower or higher risk estimates. A strong positive and statistically significant association between radiation dose and deaths from arteriosclerotic heart disease including coronary heart disease was also observed in the cohort, with an ERR of 8.78 (95% CI 2.10, 20.0). Whle associations with heart disease have been reported in some other occupational studies, the magnitude of the present association is not consistent with them and therefore needs cautious interpretation and merits further attention. At present, the relatively small number of deaths and the young age of the cohort (mean age at end of follow-up is 45 years) limit the power of the study, but further follow-up is 45 years) limit the power of the study, but further follow-up and the inclusion of the present data in an ongoing IARC combined analysis of nuclear workers from 15

  13. Molecular Investigation of the Aum Shinrikyo Anthrax Release in Kameido, Japan

    OpenAIRE

    2001-01-01

    In 1993, the Aum Shinrikyo cult aerosolized Bacillus anthracis spores over Kameido, Japan. Spore samples were obtained from the release site, cultured, and characterized by molecular genetic typing. The isolates were consistent with strain Sterne 34F2, which is used in Japan for animal prophylaxis against anthrax.

  14. Health Risk Communication in the Anthrax Vaccine Immunization Program: Lessons for the Future

    Science.gov (United States)

    2001-04-01

    percent lethal if not treated before the onset of symptoms. Once the flu-like symp- toms appear, there is no effective cure . Anthrax has no smell or...like Sudden Infant Death Syndrome, autism , or illnesses among Gulf War veterans. Any illness following a shot may be erro- neously attributed to the

  15. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    Science.gov (United States)

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax.

  16. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    NARCIS (Netherlands)

    Eker, Bilge; Yilmaz, Mahmut Deniz; Schlautmann, Stefan; Gardeniers, Johannes G.E.; Huskens, Jurriaan

    2011-01-01

    A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detecti

  17. Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy.

    Science.gov (United States)

    Kim, Seongjin; Jiao, Guan-Sheng; Moayeri, Mahtab; Crown, Devorah; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2011-04-01

    New anthrax lethal factor inhibitors (LFIs) were designed based upon previously identified potent inhibitors 1a and 2. Combining the new core structures with modifications to the C2-side chain yielded analogs with improved efficacy in the rat lethal toxin model.

  18. Purification and biophysical characterization of the core protease domain of anthrax lethal factor.

    Science.gov (United States)

    Gkazonis, Petros V; Dalkas, Georgios A; Chasapis, Christos T; Vlamis-Gardikas, Alexios; Bentrop, Detlef; Spyroulias, Georgios A

    2010-06-04

    Anthrax lethal toxin (LeTx) stands for the major virulence factor of the anthrax disease. It comprises a 90kDa highly specific metalloprotease, the anthrax lethal factor (LF). LF possesses a catalytic Zn(2+) binding site and is highly specific against MAPK kinases, thus representing the most potent native biomolecule to alter and inactivate MKK [MAPK (mitogen-activated protein kinase) kinases] signalling pathways. Given the importance of the interaction between LF and substrate for the development of anti-anthrax agents as well as the potential treatment of nascent tumours, the analysis of the structure and dynamic properties of the LF catalytic site are essential to elucidate its enzymatic properties. Here we report the recombinant expression and purification of a C-terminal part of LF (LF(672-776)) that harbours the enzyme's core protease domain. The biophysical characterization and backbone assignments ((1)H, (13)C, (15)N) of the polypeptide revealed a stable, well folded structure even in the absence of Zn(2+), suitable for high resolution structural analysis by NMR.

  19. Protective Antigen (PA) and Toxin Neutralization (TNA) Antibody Patterns in Anthrax Vaccinees Undergoing Serial Plasmapheresis

    Science.gov (United States)

    2005-03-28

    Undergoing Serial Plasmapheresis Phillip R. Pittman,1 Susan F. Leitman,2 Julio G. Barrera Oro,3 Sarah L. Norris,4 Nina M. Marano,5 Manmohan V. Ranadive...plasmapheresis on serum proteins and immunoglobulins. Transfusion 15:467–472. 12. Gold, H. 1936 . Studies on anthrax. Clinical report of ten human cases

  20. Anthrax Toxins in Context of Bacillus anthracis Spores and Spore Germination.

    Science.gov (United States)

    Cote, Christopher K; Welkos, Susan L

    2015-08-17

    The interaction of anthrax toxin or toxin components with B. anthracis spores has been demonstrated. Germinating spores can produce significant amounts of toxin components very soon after the initiation of germination. In this review, we will summarize the work performed that has led to our understanding of toxin and spore interactions and discuss the complexities associated with these interactions.

  1. Protective Immunization Against Inhalational Anthrax: A Comparison of Minimally Invasive Delivery Platforms

    Science.gov (United States)

    2004-12-15

    associ- ated with the technique. Intranasal (inl) delivery is another alternative to im delivery. It has the potential to induce mucosal immunity [21–26...Leppla SH, Fujihashi K, McGhee JR. Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization

  2. Immunological dynamics in response to two anthrax vaccines in mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu- nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac- cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza- tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex- periment when the plasma cell responses in the AVA group were reduced to a very low level. The re- sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re- sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy. These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for

  3. Immunological dynamics in response to two anthrax vaccines in mice

    Institute of Scientific and Technical Information of China (English)

    L(U) Jin; HE Rui; DONG Mei; ZHANG LiangYan; WANG XiLiang

    2008-01-01

    In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu-nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group, IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac-cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza-tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex-periment when the plasma cell responses in the AVA group were reduced to a very low level. The re-sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re-sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy, These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for vaccine

  4. Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl.

    Science.gov (United States)

    Kajfasz, Piotr; Bartoszcze, Michał; Borkowski, Piotr Karol; Basiak, Wojciech

    2014-01-01

    A 15-year-old girl was admitted to our Department with cutaneous lesion resembling black eschar. Anamnesis revealed that before getting ill she was wearing pullover made of rough sheep's wool and ornaments made of leather like straps. Cutaneous anthrax was confirmed by identification of B. anthracis in specimens from weeping ulceration, culture from black eschar, thermoprecipitation test, and bioassay on guinea pig. The girl was treated with crystalline Penicillin. She responded well to the therapy and recovered after 28 days. What attracts attention in presented case is the fact that the girl didn't belong to high risk group of human anthrax, which might lead to misdiagnosis. In 1990-1999, Poland there were reported 22 cases of anthrax - it was almost exclusively cutaneous form. In the years following 1999 antrax was reported even less often - in the period 1991-2013 it was recorded a total of 26 cutaneous anthrax cases.

  5. Detection of anthrax protective antigen (PA) using europium labeled anti-PA monoclonal antibody and time-resolved fluorescence.

    Science.gov (United States)

    Stoddard, Robyn A; Quinn, Conrad P; Schiffer, Jarad M; Boyer, Anne E; Goldstein, Jason; Bagarozzi, Dennis A; Soroka, Stephen D; Dauphin, Leslie A; Hoffmaster, Alex R

    2014-06-01

    Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63×10(-6)μM (0.551ng/ml) for PA83 and 2.51×10(-5)μM (1.58ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through the use of monoclonal antibodies to detect PA and LF in the lethal toxin complex.

  6. Combination of two candidate subunit vaccine antigens elicits protective immunity to ricin and anthrax toxin in mice.

    Science.gov (United States)

    Vance, David J; Rong, Yinghui; Brey, Robert N; Mantis, Nicholas J

    2015-01-09

    In an effort to develop combination vaccines for biodefense, we evaluated a ricin subunit antigen, RiVax, given in conjunction with an anthrax protective antigen, DNI. The combination led to high endpoint titer antibody response, neutralizing antibodies, and protective immunity against ricin and anthrax lethal toxin. This is a natural combination vaccine, since both antigens are recombinant subunit proteins that would be given to the same target population.

  7. The Evaluation of Post-Exposure Prophylaxis Models for Use in the Event of an Aerosolized Anthrax Attack

    Science.gov (United States)

    2014-09-01

    findings from the study of the accidental 1979 Sverdlovsk anthrax release in Russia , researchers have predicted that a 1- kg release of an anthrax...Equivalent Professional.” 167 Clare Stroud et al., “Commissioned Paper: A Cost and Speed Analysis of Strategies,” National Center for Biotechnology ...Bass. “Commissioned Paper: A Cost and Speed Analysis of Strategies.” National Center for Biotechnology Information, 2011. http

  8. Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

    Directory of Open Access Journals (Sweden)

    Ian Kracalik

    2014-07-01

    Full Text Available We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of (+11.95% from 1984 to 1995 followed by declining rate of -35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated "One Health" approach that takes into account the changing geographic distribution of the disease.

  9. Changing patterns of human anthrax in Azerbaijan during the post-Soviet and preemptive livestock vaccination eras.

    Science.gov (United States)

    Kracalik, Ian; Abdullayev, Rakif; Asadov, Kliment; Ismayilova, Rita; Baghirova, Mehriban; Ustun, Narmin; Shikhiyev, Mazahir; Talibzade, Aydin; Blackburn, Jason K

    2014-07-01

    We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of (+)11.95% from 1984 to 1995 followed by declining rate of -35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated "One Health" approach that takes into account the changing geographic distribution of the disease.

  10. Diagnostic performance characteristics of a rapid field test for anthrax in cattle.

    Science.gov (United States)

    Muller, Janine; Gwozdz, Jacek; Hodgeman, Rachel; Ainsworth, Catherine; Kluver, Patrick; Czarnecki, Jill; Warner, Simone; Fegan, Mark

    2015-07-01

    Although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. Here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (AICT). The AICT detects the protective antigen (PA) component of the anthrax toxin present within the blood of an animal that has died from anthrax. The test provides a result in 15min and offers the advantage of avoiding the necessity for on-site necropsy and subsequent occupational risks and environmental contamination. The specificity of the test was determined by testing samples taken from 622 animals, not infected with Bacillus anthracis. Diagnostic sensitivity was estimated on samples taken from 58 animals, naturally infected with B. anthracis collected over a 10-year period. All samples used to estimate the diagnostic sensitivity and specificity of the AICT were also tested using the gold standard of bacterial culture. The diagnostic specificity of the test was estimated to be 100% (99.4-100%; 95% CI) and the diagnostic sensitivity was estimated to be 93.1% (83.3-98.1%; 95% CI) (Clopper-Pearson method). Four samples produced false negative AICT results. These were among 9 samples, all of which tested positive for B. anthracis by culture, where there was a time delay between collection and testing of >48h and/or the samples were collected from animals that were >48h post-mortem. A statistically significant difference (P48h post-mortem 5 of 9 Se=56% (21-86.3%; 95% CI) (Clopper-Pearson method). Based upon these results a post hoc cut-off for use of the AICT of 48h post-mortem was applied, Se=100% (92.8-100%; 95% CI) and Sp=100% (99.4-100%; 95% CI). The high diagnostic sensitivity and specificity and the simplicity of the AICT enables it to be used for

  11. A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

    Science.gov (United States)

    Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

    2016-01-01

    Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important.

  12. Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system.

    Science.gov (United States)

    Cizauskas, Carrie A; Bellan, Steven E; Turner, Wendy C; Vance, Russell E; Getz, Wayne M

    2014-09-01

    Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titre determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found world-wide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis) and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titres and developed three increasingly conservative models to determine endpoint titres with more rigourous, objective mensuration. Between 52 and 87% of zebra, 0-15% of springbok and 3-52% of elephants had measurable anti-anthrax antibody titres, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as

  13. Producing, controlling, and stabilizing Pasteur's anthrax vaccine: creating a new industry and a health market.

    Science.gov (United States)

    Cassier, Maurice

    2008-06-01

    When Pasteur and Chamberland hastily set up their small biological industry to meet the agricultural demand for the anthrax vaccine, their methods for preparation and production had not yet been stabilized. The process of learning how to standardize biological products was accelerated in 1882 when vaccination accidents required the revision of production norms as the first hypotheses on fixity, inalterability, and transportability of vaccines were invalidated and replaced by procedures for continuous monitoring of the calibration of vaccines and the renewal of vaccine strains. Initially, the incompleteness and ongoing development of production standards justified Pasteur's monopoly on the production of the anthrax vaccine under his immediate supervision. Later on, the Pasteur Institute maintained control of these standards in the framework of a commercial monopoly that it established on the veterinary vaccines first sent and then cultivated abroad by the Société de Vulgarisation du Vaccin Charbonneux Pasteur, founded in 1886.

  14. Protocol for Real-Time PCR Identification of Anthrax Spores from Nasal Swabs after Broth Enrichment

    Science.gov (United States)

    Oggioni, Marco R.; Meacci, Francesca; Carattoli, Alessandra; Ciervo, Alessandra; Orru, Germano; Cassone, Antonio; Pozzi, Gianni

    2002-01-01

    A mass-screening protocol for the diagnosis of anthrax from nasal swabs based on an enrichment step in liquid medium was devised. Incubation for growth was performed in autoclavable vials and racks which allow real-time PCR analysis of sterilized cultures. A dual-color PCR was set up with primers and probes for the chromosomal marker rpoB and the plasmid marker lef. Specific primer and probe sets were designed for the differentiation of Bacillus anthracis from B. cereus and for the differentiation of the Sterne vaccine strain from field isolates and the Ames strain, which was used in the recent anthrax bioterrorist attack. The present protocol thus combines the high specificity and sensitivity of real-time PCR with excellent biosafety and the low hands-on time necessary for the processing of large numbers of samples, which is extremely important during control programs involving the processing of large numbers of samples. PMID:12409358

  15. Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women.

    Science.gov (United States)

    Meaney-Delman, Dana; Zotti, Marianne E; Creanga, Andreea A; Misegades, Lara K; Wako, Etobssie; Treadwell, Tracee A; Messonnier, Nancy E; Jamieson, Denise J

    2014-02-01

    In August 2012, the Centers for Disease Control and Prevention, in partnership with the Association of Maternal and Child Health Programs, convened a meeting of national subject matter experts to review key clinical elements of anthrax prevention and treatment for pregnant, postpartum, and lactating (P/PP/L) women. National experts in infectious disease, obstetrics, maternal fetal medicine, neonatology, pediatrics, and pharmacy attended the meeting, as did representatives from professional organizations and national, federal, state, and local agencies. The meeting addressed general principles of prevention and treatment for P/PP/L women, vaccines, antimicrobial prophylaxis and treatment, clinical considerations and critical care issues, antitoxin, delivery concerns, infection control measures, and communication. The purpose of this meeting summary is to provide updated clinical information to health care providers and public health professionals caring for P/PP/L women in the setting of a bioterrorist event involving anthrax.

  16. Modeling Tool for Decision Support during Early Days of an Anthrax Event

    Science.gov (United States)

    Meltzer, Martin I.; Shadomy, Sean; Bower, William A.; Hupert, Nathaniel

    2017-01-01

    Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat. PMID:27983505

  17. Select human anthrax protective antigen (PA) epitope-specific antibodies provide protection from lethal toxin challenge

    Science.gov (United States)

    Crowe, Sherry R.; Ash, Linda L.; Engler, Renata J. M.; Ballard, Jimmy D.; Harley, John B.; Farris, A. Darise; James, Judith A.

    2010-01-01

    Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long lasting protective immunity with reduced immunizations or providing protection through post exposure immunotherapeutics are long sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low levels of in vitro toxin neutralization capacity in their sera. Using solid phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select anti-peptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics. PMID:20533877

  18. Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event Symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lesperance, Ann M.

    2008-06-30

    On March 19, 2008, policy makers, emergency managers, and medical and Public Health officials convened in Seattle, Washington, for a workshop on Catastrophic Incident Recovery: Long-Term Recovery from an Anthrax Event. The day-long symposium was aimed at generating a dialogue about restoration and recovery through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems.

  19. 炭疽病研究进展%Research advance in anthrax

    Institute of Scientific and Technical Information of China (English)

    王刚; 刘玉峰

    2003-01-01

    @@ 2001年发生在美国的恐怖袭击事件使炭疽病(Anthrax)再次受到广泛的关注,该事件使5名受害者死于吸入性炭疽,并在全世界范围内造成了一定程度的恐慌[1,2].

  20. Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques.

    Science.gov (United States)

    Chen, Ligong; Schiffer, Jarad M; Dalton, Shannon; Sabourin, Carol L; Niemuth, Nancy A; Plikaytis, Brian D; Quinn, Conrad P

    2014-11-01

    Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined. The immunological and survival data were from 114 vaccinated and 23 control animals exposed to Bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. The vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (AVA) (BioThrax) at 0, 1, and 6 months. The immune responses were modulated by administering a range of vaccine dilutions. Together with the vaccine dilution dose and interval between the first vaccination and challenge, each of 80 immune response variables to anthrax toxin protective antigen (PA) at every available study time point was analyzed as a potential COP by logistic regression penalized by least absolute shrinkage and selection operator (LASSO) or elastic net. The anti-PA IgG level at the last available time point before challenge (last) and lymphocyte stimulation index (SI) at months 2 and 6 were identified consistently as a COP. Anti-PA IgG levels and lethal toxin neutralization activity (TNA) at months 6 and 7 (peak) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 also had statistically significant positive correlations with survival. The ratio of interleukin 4 (IL-4) mRNA to IFN-γ mRNA at month 6 also had a statistically significant negative correlation with survival. TNA had lower accuracy as a COP than did anti-PA IgG response. Following the 3-i.m. priming with AVA, the anti-PA IgG responses at the time of exposure or at month 7 were practicable and accurate metrics for correlating vaccine-induced immunity with protection against inhalation anthrax.

  1. Exoproteome analysis of a novel strain of Bacillus cereus implicated in disease resembling cutaneous anthrax.

    Science.gov (United States)

    Ghosh, Neha; Goel, Ajay Kumar; Alam, Syed Imteyaz

    2014-03-01

    Bacillus cereus belongs to B. cereus sensu lato group, shared by six other related species including Bacillus anthracis. B. anthracis is the causative agent for serious illness affecting a wide range of animals as well as humans and is a category A Biological and Toxin Warfare (BTW) agent. Recent studies indicate that a Bacillus species other than B. anthracis can cause anthrax-like disease and role of anthrax virulence plasmids (pXO1 and pXO2) on the pathogenicity of B. cereus has been documented. B. cereus strain TF5 was isolated from the tissue fluid of cutaneous anthrax-like skin lesions of a human patient from an anthrax endemic area in India. The strain harboured a PA gene, however, presence of pXO1 or pXO2-like plasmids could not be ascertained using reported primers. Abundant exoproteome of the strain in the early stationary phase was elucidated using a 2-DE MS approach and compared with that from a reference B. cereus strain. Analysis of proteins showing qualitative and quantitative differences between the two strains indicated an altered regulatory mechanism and putative role of S-layer protein and sphingomyelinase in the pathogenesis of strain TF5. Phylogenetic analysis of the S-layer protein indicated close affiliation of the strain with anthracis-like B. cereus strains such as B. cereus var. anthracis strain CI; whereas sphingomyelinase exhibited specific relationship with all the strains of B. anthracis apart from that with anthracis-like B. cereus strains.

  2. Blocking anthrax lethal toxin at the protective antigen channel by using structure-inspired drug design

    OpenAIRE

    Karginov, Vladimir A.; Nestorovich, Ekaterina M.; Moayeri, Mahtab; Leppla, Stephen H.; Bezrukov, Sergey M.

    2005-01-01

    Bacillus anthracis secretes three polypeptides: protective antigen (PA), lethal factor (LF), and edema factor (EF), which interact at the surface of mammalian cells to form toxic complexes. LF and EF are enzymes that target substrates within the cytosol; PA provides a heptameric pore to facilitate LF and EF transport into the cytosol. Other than administration of antibiotics shortly after exposure, there is currently no approved effective treatment for inhalational anthrax. Here we demonstrat...

  3. The Anthrax Terror. DOD’s Number-One Biological Threat

    Science.gov (United States)

    2000-01-01

    large quantities of anthrax and glanders organisms were grown. A Ger­ man agent, Capt Frederick Hinsch, used these to inoculate horses in Baltimore...program began receiv­ ing scrutiny under President F. W. de Klerk in the early 1990s, which led to the firing of nu­ merous scientists working the program...Rise of CB Weapons (New York: Humanities Press, 1971), 216; and Frederick R. Sidell, Ernest T. Takafuji, and David R. Franz, eds., Textbook of

  4. Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

    Science.gov (United States)

    2008-06-21

    considered to be a treat- ment of choice for anthrax, numerous reports of -lactamase- producing strains and of treatment failures have appeared in the...model of Streptococcus pneumoniae infection (28), and in a rat model of S. aureus granuloma pouch infection (27). Mice ( female CD-1; body weight, 19...may have resulted from the expression of a cryptic or inducible -lactamase (37). DISCUSSION Oritavancin, a lipoglycopeptide antibiotic that is

  5. Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors

    Directory of Open Access Journals (Sweden)

    Chandhoke Vikas

    2006-02-01

    Full Text Available Abstract Background It has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1 ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice. Results The isolated anthrax hemolytic proteins AnlB (sphingomyelinase and AnlO (cholesterol-binding pore-forming factor, as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h. Conclusion The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.

  6. Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

    Science.gov (United States)

    Zhang, Xia; Amin, Elizabeth Ambrose

    2016-01-01

    Anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, Gram-positive bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (MAPKK) enzymes and consequent disruption of key cellular signaling pathways. Antibiotics such as fluoroquinolones are capable of clearing the bacilli but have no effect on LF-mediated toxemia; LF itself therefore remains the preferred target for toxin inactivation. However, currently no LF inhibitor is available on the market as a therapeutic, partly due to the insufficiency of existing LF inhibitor scaffolds in terms of efficacy, selectivity, and toxicity. In the current work, we present novel support vector machine (SVM) models with high prediction accuracy that are designed to rapidly identify potential novel, structurally diverse LF inhibitor chemical matter from compound libraries. These SVM models were trained and validated using 508 compounds with published LF biological activity data and 847 inactive compounds deposited in the Pub Chem BioAssay database. One model, M1, demonstrated particularly favorable selectivity toward highly active compounds by correctly predicting 39 (95.12%) out of 41 nanomolar-level LF inhibitors, 46 (93.88%) out of 49 inactives, and 844 (99.65%) out of 847 Pub Chem inactives in external, unbiased test sets. These models are expected to facilitate the prediction of LF inhibitory activity for existing molecules, as well as identification of novel potential LF inhibitors from large datasets.

  7. [Vaccines against anthrax in animals, from Louis Pasteur to our day].

    Science.gov (United States)

    Shlyakhov, E; Blancou, J; Rubinstein, E

    1996-09-01

    The authors outline the history of vaccination against anthrax in animals, from the end of the 19th century to the present time. The three main steps in the production of specific vaccines are described in detail: production of vaccines from live, encapsulated bacteria, followed by vaccines from live, unencapsulated bacteria and, finally, subunit vaccines. Advantages and disadvantages of these three types of vaccine, some of which are still in use today, are described and discussed.

  8. Anthrax and the Geochemistry of Soils in the Contiguous United States

    Directory of Open Access Journals (Sweden)

    Dale W. Griffin

    2014-08-01

    Full Text Available Soil geochemical data from sample sites in counties that reported occurrences of anthrax in wildlife and livestock since 2000 were evaluated against counties within the same states (MN, MT, ND, NV, OR, SD and TX that did not report occurrences. These data identified the elements, calcium (Ca, manganese (Mn, phosphorus (P and strontium (Sr, as having statistically significant differences in concentrations between county type (anthrax occurrence versus no occurrence. Tentative threshold values of the lowest concentrations of each of these elements (Ca = 0.43 wt %, Mn = 142 mg/kg, P = 180 mg/kg and Sr = 51 mg/kg and average concentrations (Ca = 1.3 wt %, Mn = 463 mg/kg, P = 580 mg/kg and Sr = 170 mg/kg were identified from anthrax-positive counties as prospective investigative tools in determining whether an outbreak had “potential” or was “likely” at any given geographic location in the contiguous United States.

  9. Delayed toxicity associated with soluble anthrax toxin receptor decoy-Ig fusion protein treatment.

    Directory of Open Access Journals (Sweden)

    Diane Thomas

    Full Text Available Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream.

  10. The necrophagous fly anthrax transmission pathway: empirical and genetic evidence from wildlife epizootics.

    Science.gov (United States)

    Blackburn, Jason K; Van Ert, Matthew; Mullins, Jocelyn C; Hadfield, Ted L; Hugh-Jones, Martin E

    2014-08-01

    Early studies confirmed Bacillus anthracis in emesis and feces of flies under laboratory conditions, but there is little empirical field evidence supporting the roles of flies in anthrax transmission. We collected samples during outbreaks of anthrax affecting livestock and native and exotic wildlife on two ranches in West Texas (2009-2010). Sampling included animal carcasses, maggots, adult flies feeding on or within several meters of carcasses, and leaves from surrounding vegetation. Microbiology and PCR were used to detect B. anthracis in the samples. Viable B. anthracis and/or PCR-positive results were obtained from all represented sample types. Genetic analysis of B. anthracis samples using multilocus variable number tandem repeat analysis (MLVA) confirmed that each ranch represented a distinct genetic lineage. Within each ranch, we detected the same genotype of B. anthracis from carcasses, maggots, and adult flies. The results of this study provide evidence supporting a transmission cycle in which blowflies contaminate vegetation near carcasses that may then infect additional browsing animals during anthrax outbreaks in the shrubland environment of West Texas.

  11. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

    Directory of Open Access Journals (Sweden)

    Jane P. F. Bai

    2017-03-01

    Full Text Available Developing drugs to treat the toxic effects of lethal toxin (LT and edema toxin (ET produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

  12. Confirmation of acute nitrate poisoning differentiating from anthrax in three Indian indigenous cattle

    Directory of Open Access Journals (Sweden)

    Kumaresan Nagarajan

    2015-03-01

    Full Text Available This article reports cases of nitrate poisoning in Indian indigenous cattle breeds comprising two Gir cows aging 4 years each, and one Barugur cow at 1.5 years of age. The cattle with case history of sudden death and oozing of partially clotted blood from the anal opening were brought to the Central University Laboratory (CUL, Center for Animal Health Studies (CAHS, Tamil Nadu Veterinary and Animal Sciences University (TANUVAS for diagnostic investigation with a suspicion of anthrax. According to anamnesis, all the animals were clinically normal and did not reveal any abnormality on the previous day. The animals were fed with recently harvested sorghum leaves and stalks. Smears examined for anthrax were found negative. Biological test (mice inoculation for anthrax was also negative. Gross lesions on necropsy examination of the carcases were suggestive of nitrate intoxication. Finally, nitrate intoxication of these cattle was confirmed by chemical and toxicological analysis of fodder, rumen content, aqueous humor, liver, kidney and urine.

  13. A viral nanoparticle with dual function as an anthrax antitoxin and vaccine.

    Directory of Open Access Journals (Sweden)

    Darly J Manayani

    2007-10-01

    Full Text Available The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel antitoxins and vaccines that act rapidly and with minimal adverse effects. B. anthracis produces an AB-type toxin composed of the receptor-binding moiety protective antigen (PA and the enzymatic moieties edema factor and lethal factor. PA is a key target for both antitoxin and vaccine development. We used the icosahedral insect virus Flock House virus as a platform to display 180 copies of the high affinity, PA-binding von Willebrand A domain of the ANTXR2 cellular receptor. The chimeric virus-like particles (VLPs correctly displayed the receptor von Willebrand A domain on their surface and inhibited lethal toxin action in in vitro and in vivo models of anthrax intoxication. Moreover, VLPs complexed with PA elicited a potent toxin-neutralizing antibody response that protected rats from anthrax lethal toxin challenge after a single immunization without adjuvant. This recombinant VLP platform represents a novel and highly effective, dually-acting reagent for treatment and protection against anthrax.

  14. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

    2014-04-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

  15. Mortality table construction

    Science.gov (United States)

    Sutawanir

    2015-12-01

    Mortality tables play important role in actuarial studies such as life annuities, premium determination, premium reserve, valuation pension plan, pension funding. Some known mortality tables are CSO mortality table, Indonesian Mortality Table, Bowers mortality table, Japan Mortality table. For actuary applications some tables are constructed with different environment such as single decrement, double decrement, and multiple decrement. There exist two approaches in mortality table construction : mathematics approach and statistical approach. Distribution model and estimation theory are the statistical concepts that are used in mortality table construction. This article aims to discuss the statistical approach in mortality table construction. The distributional assumptions are uniform death distribution (UDD) and constant force (exponential). Moment estimation and maximum likelihood are used to estimate the mortality parameter. Moment estimation methods are easier to manipulate compared to maximum likelihood estimation (mle). However, the complete mortality data are not used in moment estimation method. Maximum likelihood exploited all available information in mortality estimation. Some mle equations are complicated and solved using numerical methods. The article focus on single decrement estimation using moment and maximum likelihood estimation. Some extension to double decrement will introduced. Simple dataset will be used to illustrated the mortality estimation, and mortality table.

  16. Anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.

    Science.gov (United States)

    Pittman, Phillip R; Cavicchia, M A; Kingsbury, J L; Johnson, N A; Barrera-Oro, J G; Schmader, T; Korman, L; Quinn, X; Ranadive, M

    2014-09-03

    Whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (AVA) (Biothrax®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (panthrax vaccine are delayed as long as 5 or more years.

  17. Approval of raxibacumab for the treatment of inhalation anthrax under the US Food and Drug Administration Animal rule

    Directory of Open Access Journals (Sweden)

    Chia-Wei eTsai

    2015-12-01

    Full Text Available On December 14, 2012, the FDA approved raxibacumab, the first product developed under Project BioShield to achieve this milestone, and the first biologic product to be approved through the FDA animal efficacy rule (or Animal Rule. Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. The approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues.

  18. Expression, Purification, and Biophysical Characterization of a Secreted Anthrax Decoy Fusion Protein in Nicotiana benthamiana

    Science.gov (United States)

    Karuppanan, Kalimuthu; Duhra-Gill, Sifti; Kailemia, Muchena J.; Phu, My L.; Lebrilla, Carlito B.; Dandekar, Abhaya M.; Rodriguez, Raymond L.; Nandi, Somen; McDonald, Karen A.

    2017-01-01

    Anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. In this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (CMG2) protein fused via a linker to the fragment crystallizable (Fc) domain of human immunoglobulin G1 in Nicotiana benthamiana plants using a transient expression system. Using the Cauliflower Mosaic Virus (CaMV) 35S promoter and co-expression with the p19 gene silencing suppressor, we were able to achieve a high level of recombinant CMG2-Fc-Apo (rCMG2-Fc-Apo) protein accumulation. Production kinetics were observed up to eight days post-infiltration, and maximum production of 826 mg/kg fresh leaf weight was observed on day six. Protein A affinity chromatography purification of the rCMG2-Fc-Apo protein from whole leaf extract and apoplast wash fluid showed the homodimeric form under non-reducing gel electrophoresis and mass spectrometry analysis confirmed the molecular integrity of the secreted protein. The N-glycosylation pattern of purified rCMG2-Fc-Apo protein was analysed; the major portion of N-glycans consists of complex type structures in both protein samples. The most abundant (>50%) N-glycan structure was GlcNAc2(Xyl)Man3(Fuc)GlcNAc2 in rCMG2-Fc-Apo recovered from whole leaf extract and apoplast wash fluid. High mannose N-glycan structures were not detected in the apoplast wash fluid preparation, which confirmed the protein secretion. Altogether, these findings demonstrate that high-level production of rCMG2-Fc-Apo can be achieved by transient production in Nicotiana benthamiana plants with apoplast targeting. PMID:28054967

  19. Biochip for the Detection of Bacillus anthracis Lethal Factor and Therapeutic Agents against Anthrax Toxins

    Science.gov (United States)

    Silin, Vitalii; Kasianowicz, John J.; Michelman-Ribeiro, Ariel; Panchal, Rekha G.; Bavari, Sina; Robertson, Joseph W. F.

    2016-01-01

    Tethered lipid bilayer membranes (tBLMs) have been used in many applications, including biosensing and membrane protein structure studies. This report describes a biosensor for anthrax toxins that was fabricated through the self-assembly of a tBLM with B. anthracis protective antigen ion channels that are both the recognition element and electrochemical transducer. We characterize the sensor and its properties with electrochemical impedance spectroscopy and surface plasmon resonance. The sensor shows a sensitivity similar to ELISA and can also be used to rapidly screen for molecules that bind to the toxins and potentially inhibit their lethal effects. PMID:27348008

  20. 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.

  1. Detecting anthrax in the palm of your hand: applications of a smartphone microscope

    Energy Technology Data Exchange (ETDEWEB)

    Erikson, Rebecca L.; Hutchison, Janine R.

    2015-11-14

    Bacillus anthracis is a bacterial pathogen that causes the disease anthrax. In 2001, B. anthracis was used in a bioterrorism attack in the United States that resulted in 22 individuals becoming infected, 5 of whom died as a result of this attack. A great deal of attention has been dedicated to responding to bioterrorism events to reduce the potential loss of lives. One such area of research has focused on the development of new technologies to detect and respond to the intentional release of bacterial pathogens such as B. anthracis.

  2. Anthrax immunization of free-ranging Roan Antelope Hippotragus Equinus in the Kruger National Park

    Directory of Open Access Journals (Sweden)

    V. de Vos

    1973-07-01

    Full Text Available An aerial method of immunization is presented as afeasible means of vaccinating free-ranging roan antelope Hippotragus equinus against anthrax in the Kruger National Park. Themethod is described in detail and the results, obtained aftertwo consecutive years of application, are noted, tabulated andevaluated. A helicopter and a fixed wing aircraft were success-fully utilized in the location of widely dispersed roan antelopeherds and to bring the operator within effective firing rangeof the animal to be darted. A disposable projectile syringe,which simultaneously administers vaccine and effectively marksthe animal for later identification, is considered a vital part inthe successful implementation of the aerial method of immunization.

  3. Telomere Length and Mortality

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Hjelmborg, Jacob V B; Gardner, Jeffrey P

    2008-01-01

    Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality...

  4. Excess mortality in hyperthyroidism

    DEFF Research Database (Denmark)

    Hjelm Brandt Kristensen, Frans; Pedersen, Dorthe Almind; Christensen, Kaare

    2012-01-01

    Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding.......Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding....

  5. Phenomenological theory of mortality

    Science.gov (United States)

    Azbel, Mark Ya.

    1997-09-01

    Extensive demographic studies relate aging to the increase in mortality, terminated by the species-specific lifespan limit. Meanwhile, recent experiments demonstrate that medfly mortality decreases at older ages, and challenge a limited lifespan paradigm. This paper proves that there exists a genetically programmed probability to die at any given age, and presents its phenomenological theory. The implications of the universal mortality law crucially depend on the cohort heterogeneity. For relatively high heterogeneity the law predicts unitarily vanishing old age mortality; this is verified with medfly data. For relatively low heterogeneity it predicts a precipitous drop in mortality fluctuations in old age. This is verified with demographic data. If comprehensive studies verify a species-specific characteristic age, then that age may be genetically manipulated. If the studies verify a unitary law of mortality, the results may be generalized to all species. A phenomenological model of mortality is presented.

  6. Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins.

    Science.gov (United States)

    Rai, Prakash; Padala, Chakradhar; Poon, Vincent; Saraph, Arundhati; Basha, Saleem; Kate, Sandesh; Tao, Kevin; Mogridge, Jeremy; Kane, Ravi S

    2006-05-01

    Numerous biological processes involve the recognition of a specific pattern of binding sites on a target protein or surface. Although ligands displayed by disordered scaffolds form stochastic rather than specific patterns, theoretical models predict that recognition will occur between patterns that are characterized by similar or "matched" statistics. Endowing synthetic biomimetic structures with statistical pattern matching capabilities may improve the specificity of sensors and resolution of separation processes. We demonstrate that statistical pattern matching enhances the potency of polyvalent therapeutics. We functionalized liposomes with an inhibitory peptide at different densities and observed a transition in potency at an interpeptide separation that matches the distance between ligand-binding sites on the heptameric component of anthrax toxin. Pattern-matched polyvalent liposomes inhibited anthrax toxin in vitro at concentrations four orders of magnitude lower than the corresponding monovalent peptide, and neutralized this toxin in vivo. Statistical pattern matching also enhanced the potency of polyvalent inhibitors of cholera toxin. This facile strategy should be broadly applicable to the detection and neutralization of toxins and pathogens.

  7. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

    Full Text Available A supramolecular platform based on self-assembled monolayers (SAMs has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP and pyrophosphate, as well as dipicolinic acid (DPA which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively.

  8. Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei; Zhang; Xin; Wang; Ping; Xie; Song-Tao; Yuan; Qing-Huai; Liu

    2015-01-01

    AIM: To prove anthrax lethal toxin(Le Tx) blocks the mitogen activated protein kinases(MAPKs) activation by degrading the MAPK/ERK kinases(MEKs) to suppress vascular endothelial growth factor(VEGF) secretion.METHODS: Human adult retinal pigmented epithelium(ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with Le Tx for additional 24, 48 or 72 h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction(RT-PCR). The conditioned medium of ARPE cells treated in different group for 48 h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays.Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting. RESULTS: In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase(ERK1/2) and p38 in the ARPE cell line was blocked by anthrax Le Tx. Le Tx also inhibited high glucose induced ARPE cell over proliferation.CONCLUSION: Le Tx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism.

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

    Science.gov (United States)

    Devera, T Scott; Prusator, Dawn K; Joshi, Sunil K; Ballard, Jimmy D; Lang, Mark L

    2015-06-25

    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.

  10. Detection of anthrax lef with DNA-based photonic crystal sensors

    Science.gov (United States)

    Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

    2011-12-01

    Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

  11. Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available BACKGROUND: A key step of anthrax toxin action involves the formation of a protein-translocating pore within the endosomal membrane by the Protective Antigen (PA moiety. Formation of this transmembrane pore by PA involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects on pore formation, protein translocation, and cytotoxicity, of mutating two phenylalanines, F313 and F314, that lie at the tip the beta barrel, and a third one, F324, that lies part way up the barrel. CONCLUSIONS/SIGNIFICANCE: Our results show that the function of these phenylalanine residues is to mediate membrane insertion and formation of stable transmembrane channels. Unlike F427, a key luminal residue in the cap of the pore, F313, F314, and F324 do not directly affect protein translocation through the pore. Our findings add to our knowledge of structure-function relationships of a key virulence factor of the anthrax bacillus.

  12. The Mountain Meadows Massacre and "poisoned springs": scientific testing of the more recent, anthrax theory.

    Science.gov (United States)

    Perego, Ugo A; Achilli, Alessandro; Ekins, Jayne E; Milani, Lucio; Lari, Martina; Pilli, Elena; Brown, Alexis; Price, Erin P; Wolken, Spenser R; Matthews, Molly; Allen, Christina A; Pearson, Talima R; Angerhofer, Norman; Caramelli, David; Kupferschmid, Tim; Keim, Paul S; Woodward, Scott R

    2013-01-01

    It has been recorded that one of the possible causes that eventually escalated into the 1857 manslaughter at Mountain Meadows in Southern Utah was the poisoning of an open spring by the Fancher-Baker party as they crossed the Utah territory on their way from Arkansas to California. Historical accounts report that a number of cattle died, followed by human casualties from those that came in contact with the dead animals. Even after the Arkansas party departed, animals continued to perish and people were still afflicted by some unknown plague. Proctor Hancock Robison, a local 14-year-old boy, died shortly after skinning one of the "poisoned" cows. A careful review of the historical records, along with the more recent scientific literature, seems to exclude the likelihood of actual poisoning in favor of a more recent theory that would point to the bacterium Bacillus anthracis as the possible cause of human and animal deaths. In order to test this hypothesis, Proctor's remains were exhumed, identified through mitochondrial DNA analysis, and tested for the presence of anthrax spores. Although preliminary testing of remains and soil was negative, description of the clinical conditions that affected Proctor and other individuals does not completely rule out the hypothesis of death by anthrax.

  13. Detection of anthrax lef with DNA-based photonic crystal sensors.

    Science.gov (United States)

    Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

    2011-12-01

    Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

  14. Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.

    Directory of Open Access Journals (Sweden)

    Heather M Scobie

    Full Text Available The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA toxin subunit from forming pores until exposure to low pH. PA forms pores at pH approximately 6.0 or below when it is bound to ANTXR1, but only at pH approximately 5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation.

  15. Examining the CDCynergy Event Assessment Tool: an investigation of the anthrax crisis in Boca Raton, Florida.

    Science.gov (United States)

    McIntyre, J J; Venette, Steven

    2006-09-01

    This paper examines the dependability of the Event Assessment Tool over time. The latter is part of a CD-ROM--Emergency Risk Communication CDCynergy--distributed primarily to public information officers in the United States by the Centers for Disease Control and Prevention. The Event Assessment Tool is designed to aid emergency professionals in identifying the magnitude of a crisis event and to suggest appropriate actions to confront such a situation. Applied twice during the 2001 anthrax bioterrorism crisis in Boca Raton, Florida, the tool functioned in a binary manner by first indicating a moderate crisis level (on 4 October) and then four days later (on 8 October) a highly intense crisis, suggesting that it is time sensitive. This anthrax event provides an opportunity for crisis and disaster managers to understand the dynamic nature of crises. Rapid changes during these types of events suggest that any metric used to predict intensity must account for this variability. Additional limitations and implications of the tool are discussed.

  16. Lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge.

    Science.gov (United States)

    Hutt, Julie A; Lovchik, Julie A; Drysdale, Melissa; Sherwood, Robert L; Brasel, Trevor; Lipscomb, Mary F; Lyons, C Rick

    2014-12-01

    Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. To better understand the contribution of these toxins to the disease pathophysiology in vivo, we used B. anthracis Ames strain and isogenic toxin deletion mutants derived from the Ames strain to examine the role of lethal toxin and edema toxin after pulmonary spore challenge of cynomolgus macaques. Lethal toxin, but not edema toxin, was required to induce sustained bacteremia and death after pulmonary challenge with spores delivered via bronchoscopy. After intravenous challenge with bacilli to model the systemic phase of infection, lethal toxin contributed to bacterial proliferation and subsequent host death to a greater extent than edema toxin. Deletion of protective antigen resulted in greater loss of virulence after intravenous challenge with bacilli than deletion of lethal toxin or edema toxin alone. These findings are consistent with the ability of anti-protective antigen antibodies to prevent anthrax and suggest that lethal factor is the dominant toxin that contributes to the escape of significant numbers of bacilli from the thoracic cavity to cause anthrax after inhalation challenge with spores.

  17. Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

    Science.gov (United States)

    Quinn, Conrad P; Semenova, Vera A; Elie, Cheryl M; Romero-Steiner, Sandra; Greene, Carolyn; Li, Han; Stamey, Karen; Steward-Clark, Evelene; Schmidt, Daniel S; Mothershed, Elizabeth; Pruckler, Janet; Schwartz, Stephanie; Benson, Robert F; Helsel, Leta O; Holder, Patricia F; Johnson, Scott E; Kellum, Molly; Messmer, Trudy; Thacker, W Lanier; Besser, Lilah; Plikaytis, Brian D; Taylor, Thomas H; Freeman, Alison E; Wallace, Kelly J; Dull, Peter; Sejvar, Jim; Bruce, Erica; Moreno, Rosa; Schuchat, Anne; Lingappa, Jairam R; Martin, Sandra K; Walls, John; Bronsdon, Melinda; Carlone, George M; Bajani-Ari, Mary; Ashford, David A; Stephens, David S; Perkins, Bradley A

    2002-10-01

    The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

  18. Patients' request for and emergency physicians' prescription of antimicrobial prophylaxis for anthrax during the 2001 bioterrorism-related outbreak

    Directory of Open Access Journals (Sweden)

    Aber Robert C

    2005-01-01

    Full Text Available Abstract Background Inappropriate use of antibiotics by individuals worried about biological agent exposures during bioterrorism events is an important public health concern. However, little is documented about the extent to which individuals with self-identified risk of anthrax exposure approached physicians for antimicrobial prophylaxis during the 2001 bioterrorism attacks in the United States. Methods We conducted a telephone survey of randomly selected members of the Pennsylvania Chapter of the American College of Emergency Physicians to assess patients' request for and emergency physicians' prescription of antimicrobial agents during the 2001 anthrax attacks. Results Ninety-seven physicians completed the survey. Sixty-four (66% respondents had received requests from patients for anthrax prophylaxis; 16 (25% of these physicians prescribed antibiotics to a total of 23 patients. Ten physicians prescribed ciprofloxacin while 8 physicians prescribed doxycycline. Conclusion During the 2001 bioterrorist attacks, the majority of the emergency physicians we surveyed encountered patients who requested anthrax prophylaxis. Public fears may lead to a high demand for antibiotic prophylaxis during bioterrorism events. Elucidation of the relationship between public health response to outbreaks and outcomes would yield insights to ease burden on frontline clinicians and guide strategies to control inappropriate antibiotic allocation during bioterrorist events.

  19. Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Abdelkrim Alileche

    2005-10-01

    Full Text Available Many pathogens have acquired strategies to combat the immune response. Bacillus anthracis interferes with host defenses by releasing anthrax lethal toxin (LT, which inactivates mitogen-activated protein kinase pathways, rendering dendritic cells (DCs and T lymphocytes nonresponsive to immune stimulation. However, these cell types are considered resistant to killing by LT. Here we show that LT kills primary human DCs in vitro, and murine DCs in vitro and in vivo. Kinetics of LT-mediated killing of murine DCs, as well as cell death pathways induced, were dependent upon genetic background: LT triggered rapid necrosis in BALB/c-derived DCs, and slow apoptosis in C57BL/6-derived DCs. This is consistent with rapid and slow killing of LT-injected BALB/c and C57BL/6 mice, respectively. We present evidence that anthrax LT impairs adaptive immunity by specifically targeting DCs. This may represent an immune-evasion strategy of the bacterium, and contribute to anthrax disease progression. We also established that genetic background determines whether apoptosis or necrosis is induced by LT. Finally, killing of C57BL/6-derived DCs by LT mirrors that of human DCs, suggesting that C57BL/6 DCs represent a better model system for human anthrax than the prototypical BALB/c macrophages.

  20. Maintaining U.S. Government Business Operations within the National Capital Region after an Aerosolized Anthrax Attack

    Science.gov (United States)

    2008-04-28

    Association, Volume 287, Number 17, 2237. 18 John G. Bartlett, Thomas V. Ingelsby, Jr., and Luciana Borio, “Management of Anthrax,” October 1, 2002...Human Services and the Secretary of Homeland Security, September 20, 2007. 46 Inglesby, 2244. 47 Luciana L. Borio, M.D., “CBN Report: Immunological

  1. Environmental temperature and mortality

    OpenAIRE

    Näyhä, Simo

    2005-01-01

    In Finland, mortality increases steeply in autumn, reaches a peak during the Christhmas holidays and declines slowly towards a trough in August. The relative excess in daily mortality (peak vs. trough) is 30% for coronary heart disease, 40% for cerebral vascular accidents and 90% for diseases of the respiratory organs. There is a secondary peak in Midsummer, especially in coronary deaths of working aged men. Mortality is lowest at mean daily temperature of +14 degrees C, and it increases slow...

  2. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben;

    2007-01-01

    OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into chil......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...

  3. Maternal mortality from hemorrhage.

    Science.gov (United States)

    Haeri, Sina; Dildy, Gary A

    2012-02-01

    Hemorrhage remains as one of the top 3 obstetrics related causes of maternal mortality, with most deaths occurring within 24-48 hours of delivery. Although hemorrhage related maternal mortality has declined globally, it continues to be a vexing problem. More specifically, the developing world continue to shoulder a disproportionate share of hemorrhage related deaths (99%) compared with industrialized nations (1%). Given the often preventable nature of death from hemorrhage, the cornerstone of effective mortality reduction involves risk factor identification, quick diagnosis, and timely management. In this monograph we will review the epidemiology, etiology, and preventative measures related to maternal mortality from hemorrhage.

  4. Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like Attenuated Toxigenic Nonencapsulated B. anthracis Sterne in Rabbits and Mice

    Science.gov (United States)

    2011-08-01

    Microbiology. All Rights Reserved. Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like...G9241 for mice requires the presence of both plasmids. The Bacillus cereus group, of which Bacillus anthracis, Bacil- lus thuringiensis , and B... Bacillus cereus G9241 Makes Anthrax Toxin and Capsule like Highly Virulent B. anthracis Ames but Behaves like Attenuated Toxigenic Nonencapsulated B

  5. Mortality in ankylosing spondylitis

    DEFF Research Database (Denmark)

    Exarchou, Sofia; Lie, Elisabeth; Lindström, Ulf;

    2016-01-01

    OBJECTIVES: Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. METHODS: Nationwide cohorts of patients with AS diagnosed at rheumatology...

  6. Mortality associated with phaeochromocytoma

    NARCIS (Netherlands)

    Prejbisz, A.; Lenders, J.W.M.; Eisenhofer, G.; Januszewicz, A.

    2013-01-01

    Two major categories of mortality are distinguished in patients with phaeochromocytoma. First, the effects of excessive circulating catecholamines may result in lethal complications if the disease is not diagnosed and/or treated timely. The second category of mortality is related to development of m

  7. Facilitation of risk communication during the anthrax attacks of 2001: the organizational backstory.

    Science.gov (United States)

    Chess, Caron; Clarke, Lee

    2007-09-01

    The anthrax attacks of 2001 created risk communication problems that cannot be fully understood without appreciating the dynamics among organizations. Case studies of communication in New Jersey, consisting of interviews with a range of participants, found that existing organizational and professional networks facilitated trust among decisionmakers. This interpersonal trust improved communication among agencies and thereby risk communication with the public. For example, "white powder scares" were a problem even in places without contamination. Professionals' trust in each other was vital for responding productively. Conversely, organizational challenges, including conflict among agencies, hindered communication with key audiences. Although centralization and increased control are often seen as the remedy for communicative confusion, they also can quash the improvisational responses needed during crises.

  8. Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome.

    Directory of Open Access Journals (Sweden)

    Jonathan L Levinsohn

    Full Text Available NOD-like receptor (NLR proteins (Nlrps are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis and maturation of IL-1β and IL-18. Anthrax lethal toxin (LT induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR Nlrp1 inflammasome. Here we show that LT cleaves rat Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 β release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.

  9. Initiating informatics and GIS support for a field investigation of Bioterrorism: The New Jersey anthrax experience

    Directory of Open Access Journals (Sweden)

    Skinner Ric

    2003-11-01

    Full Text Available Abstract Background The investigation of potential exposure to anthrax spores in a Trenton, New Jersey, mail-processing facility required rapid assessment of informatics needs and adaptation of existing informatics tools to new physical and information-processing environments. Because the affected building and its computers were closed down, data to list potentially exposed persons and map building floor plans were unavailable from the primary source. Results Controlling the effects of anthrax contamination required identification and follow-up of potentially exposed persons. Risk of exposure had to be estimated from the geographic relationship between work history and environmental sample sites within the contaminated facility. To assist in establishing geographic relationships, floor plan maps of the postal facility were constructed in ArcView Geographic Information System (GIS software and linked to a database of personnel and visitors using Epi Info and Epi Map 2000. A repository for maintaining the latest versions of various documents was set up using Web page hyperlinks. Conclusions During public health emergencies, such as bioterrorist attacks and disease epidemics, computerized information systems for data management, analysis, and communication may be needed within hours of beginning the investigation. Available sources of data and output requirements of the system may be changed frequently during the course of the investigation. Integrating data from a variety of sources may require entering or importing data from a variety of digital and paper formats. Spatial representation of data is particularly valuable for assessing environmental exposure. Written documents, guidelines, and memos important to the epidemic were frequently revised. In this investigation, a database was operational on the second day and the GIS component during the second week of the investigation.

  10. Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax.

    Science.gov (United States)

    Chen, Zhaochun; Schneerson, Rachel; Lovchik, Julie A; Dai, Zhongdong; Kubler-Kielb, Joanna; Agulto, Liane; Leppla, Stephen H; Purcell, Robert H

    2015-08-01

    The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.

  11. Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

    Science.gov (United States)

    Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

    2016-08-01

    Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets.

  12. A heterodimer of a VHH (variable domains of camelid heavy chain-only) antibody that inhibits anthrax toxin cell binding linked to a VHH antibody that blocks oligomer formation is highly protective in an anthrax spore challenge model.

    Science.gov (United States)

    Moayeri, Mahtab; Leysath, Clinton E; Tremblay, Jacqueline M; Vrentas, Catherine; Crown, Devorah; Leppla, Stephen H; Shoemaker, Charles B

    2015-03-06

    Anthrax disease is caused by a toxin consisting of protective antigen (PA), lethal factor, and edema factor. Antibodies against PA have been shown to be protective against the disease. Variable domains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. Two classes of neutralizing VHHs were identified recognizing distinct, non-overlapping epitopes. One class recognizes domain 4 of PA at a well characterized neutralizing site through which PA binds to its cellular receptor. A second neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits conversion of the PA oligomer from "pre-pore" to its SDS and heat-resistant "pore" conformation while not preventing cleavage of full-length 83-kDa PA (PA83) by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The antibody prevents endocytosis of the cell surface-generated PA63 subunit but not preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and protected mice from anthrax toxin challenge with much better efficacy than the separate component VHHs. The VNA protected virtually all mice when separately administered at a 1:1 ratio to toxin and protected mice against Bacillus anthracis spore infection. Thus, our studies show the potential of VNAs as anthrax therapeutics. Due to their simple and stable nature, VNAs should be amenable to genetic delivery or administration via respiratory routes.

  13. 2000~2009年广西炭疽流行病学分析%Epidemiological analysis of anthrax in Guangxi Province from 2000 to 2009

    Institute of Scientific and Technical Information of China (English)

    梁江明; 邓秋云; 曾竣; 廖驰真; 吴秀玲

    2011-01-01

    Aim To analyse the epidemiological features of anthrax in Guangxi Province from 2000 to 2009 and provide scientific basis for prevention and control of the disease. Methods The The data concerning prevalence and control of anthrax in Guangxi from 2000 to 2009 were collected and analyzed. Results The prevalence of anthrax occurred in Guangxi every year,and the prevalence of anthrax in livestock often frequently occurred prior to the epidemic in human beings. The anthrax in Guangxi was of the agricultural type and was widespread without apparent periodic characteristic,most of the anthrax eases were farmers and were infected by slaughtering and eating the sick livestock. The incidence of anthrax was from 0.0015/100 000 to 0.22/100 000 population. Most of the anthrax cases were cutaneous anthrax. Conclusion To educate people not slaughter or eat or sell sick livestock and process correctly the corpses of sick livestock are the key measures for prevention and control the anthrax..%目的 了解广西炭疽流行病学特征,为预防与控制本病提供科学依据.方法 对2000~2009年广西炭疽疫情报告及其相关资料进行回顾性分析.结果 广西炭疽病例每年均有发生.人间炭疽流行常继发于畜间炭疽流行,以局部暴发为主,流行类型属农业型,分布广泛.流行无明显的周期性,发病率在0.0015/10万~0.22/10万之间.受害者主要是农民,大多数都是由于剖食病死家畜而感染,以皮肤型炭疽最为多见.结论 认真做好炭疽防治知识的宣传教育工作.做到不剖杀、不分食、不出售病死家畜,并妥善处理好病死家畜尸体是防治本病的关键.

  14. Mortality after shoulder arthroplasty

    DEFF Research Database (Denmark)

    Amundsen, Alexander; Rasmussen, Jeppe Vejlgaard; Olsen, Bo Sanderhoff

    2016-01-01

    BACKGROUND: The primary aim was to quantify the 30-day, 90-day, and 1-year mortality rates after primary shoulder replacement. The secondary aims were to assess the association between mortality and diagnoses and to compare the mortality rate with that of the general population. METHODS: The study...... included 5853 primary operations reported to the Danish Shoulder Arthroplasty Registry between 2006 and 2012. Information about deaths was obtained from the Danish Cause of Death Register and the Danish Civil Registration System. Age- and sex-adjusted control groups were retrieved from Statistics Denmark...

  15. Mortality in Asia.

    Science.gov (United States)

    1981-01-01

    Although the general trend in mortality between 1950 and 1975 in South and East Asia has been downward, there is considerable country-to-country variation in the rate of decline. In countries where combined economic, social, and political circumstances resulted in controlling the disease spectrum (e.g., China, Malaysia, Sri Lanka), mortality levels declined to those seen in low-mortality countries. In most of the large countries of the region however, mortality declined at a slower rate, even slowing down considerably in the 1970's while the death rates remained high (e.g., India, Bangladesh, Thailand, Philippines); this slowing down of mortality level is attributed essentially to the poverty-stricken masses of society which were not able to take advantage of social, technological, and health-promoting behavioral changes conducive to mortality decline. Infant mortality levels, although declining since 1950, followed the same dismal pattern of the general mortality level. The rate varies from less than 10/1000 live births (Japan) to more than 140/1000 (Bangladesh, Laos, Nepal). Generally, rural areas exhibited higher infant mortality than urban areas. The level of child mortality declines with increases in the mother's educational level in Bangladesh, India, Indonesia, Sri Lanka, and Thailand. The largest decline in child mortality occurs when at least 1 parent has secondary education. The premature retardation of mortality decline is caused by several factors: economic development, nutrition and food supply, provision and adequacy of health services, and demographic trends. The outlook for the year 2000 for most of Asia's countries will depend heavily on significant population increases. In most countries, particularly in South Asia, population is expected to increase by 75%, much of it in rural areas and among poorer socioeconomic groups. In view of this, Asia's health planners and policymakers will have to develop health policies which will strike a balance

  16. Studies of the Biological and Molecular Basis of the Inhibition of Activity of Phagocytic Cells by Anthrax Toxin

    Science.gov (United States)

    1985-03-01

    activity of the anthrax toxin which could provide clues to the nature of its antiphagocytic effect and its contribution to virulence of B. anthracs...ccmponents makes this unlikely. Early observations on the nature of this toxin tended to emphasize the requirement for cooperative action of the three...with oxidizable substances in the ocmplex system. evidently, endogenous amines. especially taurine , are the most active of the available receptors, and

  17. 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.

  18. Computational Modeling of Aerosol Hazard Arising from the Opening of an Anthrax Letter in an Open-Office Complex

    Science.gov (United States)

    Lien, F. S.; Ji, H.; Yee, E.

    Early experimental work, conducted at Defence R&D Canada — Suffield, measured and characterized the personal and environmental contamination associated with the simulated opening of anthrax-tainted letters under a number of different scenarios. A better understanding of the physical and biological processes is considerably significant for detecting, assessing, and formulating potential mitigation strategies for managing these risks. These preliminary experimental investigations have been extended to simulate the contamination from the opening of anthrax-tainted letters in an Open-Office environment using Computational Fluid Dynamics (CFD). Bacillus globigii (BG) was used as a biological simulant for anthrax, with 0.1 gram of the simulant released from opened letters in the experiments conducted. The accuracy of the model for prediction of the spatial distribution of BG spores in the office is first assessed quantitatively by comparison with measured SF6 concentrations (the baseline experiment), and then qualitatively by comparison with measured BG concentrations obtained under a number of scenarios, some involving people moving within various offices.

  19. Generation of protective immune response against anthrax by oral immunization with protective antigen plant-based vaccine.

    Science.gov (United States)

    Gorantala, Jyotsna; Grover, Sonam; Rahi, Amit; Chaudhary, Prerna; Rajwanshi, Ravi; Sarin, Neera Bhalla; Bhatnagar, Rakesh

    2014-04-20

    In concern with frequent recurrence of anthrax in endemic areas and inadvertent use of its spores as biological weapon, the development of an effective anthrax vaccine suitable for both human and veterinary needs is highly desirable. A simple oral delivery through expression in plant system could offer promising alternative to the current methods that rely on injectable vaccines extracted from bacterial sources. In the present study, we have expressed protective antigen (PA) gene in Indian mustard by Agrobacterium-mediated transformation and in tobacco by plastid transformation. Putative transgenic lines were verified for the presence of transgene and its expression by molecular analysis. PA expressed in transgenic lines was biologically active as evidenced by macrophage lysis assay. Intraperitoneal (i.p.) and oral immunization with plant PA in murine model indicated high serum PA specific IgG and IgA antibody titers. PA specific mucosal immune response was noted in orally immunized groups. Further, antibodies indicated lethal toxin neutralizing potential in-vitro and conferred protection against in-vivo toxin challenge. Oral immunization experiments demonstrated generation of immunoprotective response in mice. Thus, our study examines the feasibility of oral PA vaccine expressed in an edible plant system against anthrax.

  20. Mortality in spondylarthritis.

    Science.gov (United States)

    Prati, Clément; Claudepierre, Pascal; Pham, Thao; Wendling, Daniel

    2011-10-01

    Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that can lead to chronic pain in axial and peripheral joints and to functional impairments after several years. Excess mortality has been reported in patients with AS. We reviewed recent studies of patients with AS who were treated and monitored according to the improved methods developed in the past few years, without radiation therapy. Our results do not support excess mortality in these patients. Long-term follow-up data from patients enrolled in biologics registries will provide additional information. Cardiovascular disease is the leading cause of death in patients with AS, as in the general population. However, the cardiovascular mortality rate may be slightly increased in patients with AS, probably as a result of dyslipidemia and early endothelial dysfunction. Similarly, and as expected, there is excess mortality related to the spinal disease itself and to renal and gastrointestinal disease. More surprisingly, alcohol abuse and injury or suicide cause excess mortality compared to the general population. In the absence of radiation or radium-224 therapy, and regardless of the other treatments used, the evidence does not support an increased rate of lymphoma or other malignancies compared to the general population. In this review, we discuss the causes and rates of mortality in patients with AS.

  1. A Hierarchical Distance Sampling Approach to Estimating Mortality Rates from Opportunistic Carcass Surveillance Data.

    Science.gov (United States)

    Bellan, Steve E; Gimenez, Olivier; Choquet, Rémi; Getz, Wayne M

    2013-04-01

    Distance sampling is widely used to estimate the abundance or density of wildlife populations. Methods to estimate wildlife mortality rates have developed largely independently from distance sampling, despite the conceptual similarities between estimation of cumulative mortality and the population density of living animals. Conventional distance sampling analyses rely on the assumption that animals are distributed uniformly with respect to transects and thus require randomized placement of transects during survey design. Because mortality events are rare, however, it is often not possible to obtain precise estimates in this way without infeasible levels of effort. A great deal of wildlife data, including mortality data, is available via road-based surveys. Interpreting these data in a distance sampling framework requires accounting for the non-uniformity sampling. Additionally, analyses of opportunistic mortality data must account for the decline in carcass detectability through time. We develop several extensions to distance sampling theory to address these problems.We build mortality estimators in a hierarchical framework that integrates animal movement data, surveillance effort data, and motion-sensor camera trap data, respectively, to relax the uniformity assumption, account for spatiotemporal variation in surveillance effort, and explicitly model carcass detection and disappearance as competing ongoing processes.Analysis of simulated data showed that our estimators were unbiased and that their confidence intervals had good coverage.We also illustrate our approach on opportunistic carcass surveillance data acquired in 2010 during an anthrax outbreak in the plains zebra of Etosha National Park, Namibia.The methods developed here will allow researchers and managers to infer mortality rates from opportunistic surveillance data.

  2. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

    Directory of Open Access Journals (Sweden)

    Matthew D Reed

    Full Text Available Protective antigen (PA, one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax. Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel, elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.

  3. Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

    Science.gov (United States)

    Reed, Matthew D; Wilder, Julie A; Mega, William M; Hutt, Julie A; Kuehl, Philip J; Valderas, Michelle W; Chew, Lawrence L; Liang, Bertrand C; Squires, Charles H

    2015-01-01

    Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.

  4. Protein- and DNA-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge with Bacillus cereus G9241.

    Science.gov (United States)

    Palmer, John; Bell, Matt; Darko, Christian; Barnewall, Roy; Keane-Myers, Andrea

    2014-11-01

    In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model.

  5. The mortality of companies

    Science.gov (United States)

    Daepp, Madeleine I. G.; Hamilton, Marcus J.; West, Geoffrey B.; Bettencourt, Luís M. A.

    2015-01-01

    The firm is a fundamental economic unit of contemporary human societies. Studies on the general quantitative and statistical character of firms have produced mixed results regarding their lifespans and mortality. We examine a comprehensive database of more than 25 000 publicly traded North American companies, from 1950 to 2009, to derive the statistics of firm lifespans. Based on detailed survival analysis, we show that the mortality of publicly traded companies manifests an approximately constant hazard rate over long periods of observation. This regularity indicates that mortality rates are independent of a company's age. We show that the typical half-life of a publicly traded company is about a decade, regardless of business sector. Our results shed new light on the dynamics of births and deaths of publicly traded companies and identify some of the necessary ingredients of a general theory of firms. PMID:25833247

  6. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    Science.gov (United States)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-01-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  7. Differential dependence on N-glycosylation of anthrax toxin receptors CMG2 and TEM8.

    Directory of Open Access Journals (Sweden)

    Sarah Friebe

    Full Text Available ANTXR 1 and 2, also known as TEM8 and CMG2, are two type I membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. Here we have analyzed the importance of N-glycosylation on folding, trafficking and ligand binding of these closely related proteins. We find that TEM8 has a stringent dependence on N-glycosylation. The presence of at least one glycan on each of its two extracellular domains, the vWA and Ig-like domains, is indeed necessary for efficient trafficking to the cell surface. In the absence of any N-linked glycans, TEM8 fails to fold correctly and is recognized by the ER quality control machinery. Expression of N-glycosylation mutants reveals that CMG2 is less vulnerable to sugar loss. The absence of N-linked glycans in one of the extracellular domains indeed has little impact on folding, trafficking or receptor function of the wild type protein expressed in tissue culture cells. N-glycans do, however, seem required in primary fibroblasts from human patients. Here, the presence of N-linked sugars increases the tolerance to mutations in cmg2 causing the rare genetic disease Hyaline Fibromatosis Syndrome. It thus appears that CMG2 glycosylation provides a buffer towards genetic variation by promoting folding of the protein in the ER lumen.

  8. Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

    Directory of Open Access Journals (Sweden)

    Maria Estrella Jimenez

    2012-11-01

    Full Text Available Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF, an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.

  9. Incorporating retrospective clustering into a prospective Cusum methodology for anthrax: evaluating the effects of disease expectation.

    Science.gov (United States)

    Kracalik, Ian; Lukhnova, Larissa; Aikimbayev, Alim; Pazilov, Yerlan; Temiralyeva, Gulnara; Blackburn, Jason K

    2011-03-01

    We analysed livestock anthrax in Kazakhstan from 1960-2006, using a prospective CUSUM to examine the affects of expectation on the detection of spatio-temporal clusters. Three methods for deriving baselines were used for CUSUM; a standard z-score, AVG, a spatially-weighted z-score derived from Local Moran's I, LISA, and a moving-window average, MWA. LISA and AVG elicited alarm signals in the second year that did not return below threshold during the 47-year period, while MWA signaled an alarm at year four and relented at year fifteen. The number of spatial clusters elicited varied: LISA n=16, AVG n=11, and MWA n=3, although there were clusters present around Shymkent, in south-central Kazakhstan, in each method. The results illustrate that the selection of a baseline with an unknown background population has a significant effect on the ability to detect the onset of clusters in space and in time when employing a CUSUM methodology.

  10. Development of a Zealand white rabbit deposition model to study inhalation anthrax

    Energy Technology Data Exchange (ETDEWEB)

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

    2016-01-28

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  11. Diagnosis, treatment and prevention of anthrax%炭疽病的诊治和预防

    Institute of Scientific and Technical Information of China (English)

    徐婷婷; 沈叙庄; 杨永弘

    2003-01-01

    @@ 炭疽(Anthrax)是一种由炭疽杆菌(B. antracis)引起的人畜共患的急性传染病,主要发生在有蹄类哺乳动物,如牛、马、羊、猪、犬,人类通过直接或间接接触、吸入或食入病菌而致病.公元前300年希波克拉底就已描述此病,它曾经在全球范围出现暴发流行,因其本身的生物学特征及感染方式而被人们作为生物武器用于战争.2001年9月11日美国遭受恐怖主义袭击后,陆续出现炭疽感染患者,已确诊22名,11例为皮肤炭疽,11例为吸入性炭疽,9名吸入性炭疽患者曾经接触过装有炭疽杆菌的信件,其中6人死亡.因此我们有必要对该病深入了解.

  12. Lanthanide-functionalized silver nanoparticles for detection of an anthrax biomarker and test paper fabrication

    Science.gov (United States)

    Tan, Hongliang; Li, Qian; Ma, Chanjiao; Song, Yonghai; Xu, Fugang; Chen, Shouhui; Wang, Li

    2014-01-01

    It is highly desirable to develop a simple and sensitive analytical method for detection of anthrax biomarker (dipicolinic acid, DPA) because of its dangerous nature. In this work, we developed a fluorescent sensor for DPA detection based on terbium ion-functionalized silver nanoparticles with an average size of 6.7 nm (AgNPs-Tb3+). The fluorescent intensity of Tb-DPA complex on the surface of AgNPs was two times higher than that of Tb-DPA complex alone in a solution phase due to the metal-enhanced fluorescence (MEF) effect of AgNPs. The proposed fluorescent sensor exhibits excellent selectivity and high sensitivity for DPA. Importantly, a test paper for DPA detection was fabricated for the first time by the integration of AgNPs-Tb3+ onto the nitrocellulose membrane. Owing to the MEF effect of AgNPs, the lowest detectable concentration of the test paper-integrated AgNPs-Tb3+ for DPA by naked eyes is 10 times lower than that of the test paper-integrated Tb3+ alone. We believe that the presented strategy may open up new avenues to the development of portable and robust-sensing platforms based on functional hybrid materials.

  13. Rapid and label-free screening and identification of Anthrax simulants by Surface Enhanced Raman Spectroscopy

    Science.gov (United States)

    Lai, Antonia; Almaviva, Salvatore; Spizzichino, Valeria; Palucci, Antonio; Addari, Lorella; Luciani, Domenico; Mengali, Sandro; Marquette, Christophe; Berthuy, Ophélie; Jankiewicz, Bartlomiej; Pierno, Luigi

    2014-10-01

    In the framework of RAMBO (Rapid-Air Monitoring particle against biological threats) project of the European Defense Agency (EDA), the feasibility of an unattended Surface Enhanced Raman Spectroscopy (SERS) sensor for biological threats detection was investigated. Its main goal concern Bacillus anthrax detection, both as vegetative cells and endospores. However since such bacteria are classified in Risk Group 3 (very dangerous microorganism), Bacillus thuringiensis and Bacillus atrophaeus were used as simulants. In order to bind selectively the target bacilli, Phages properly selected were immobilized on an active commercially available SERS substrate (functionalization). The Phages are a type of virus that infect selectively, by means of receptors, specific bacteria. Moreover they can resist on water or air environments without losing their binding capabilities. The sensing surface was characterized by standard micro-Raman equipments to assess the background Raman features. The Raman measurements have been carried out from 10X to 100X of magnification to differentiate between average and local features. Moreover the fast response was acquired by limiting the measure time at less than 1 minute. Samples of vegetative cells and endospores of Bacilli were randomly dispersed on the functionalized SERS substrates. The results obtained are promising: samples with and without bacilli could be distinguished one from the other. This is a step toward the use of SERS as an effective and fast technique for early warning of biological threats.

  14. Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.

    Directory of Open Access Journals (Sweden)

    Robert J Fieldhouse

    Full Text Available Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences--including a primary sequence pattern--to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data--and we need high-throughput validation--our approach provides insight into the newest toxin ADP-ribosyltransferases.

  15. The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations.

    Science.gov (United States)

    Schuch, Raymond; Fischetti, Vincent A

    2009-08-12

    Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

  16. The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations.

    Directory of Open Access Journals (Sweden)

    Raymond Schuch

    Full Text Available Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

  17. 抗炭疽毒素的小分子药物研究进展%Recent advances in development of small molecule inhibitors of anthrax toxin

    Institute of Scientific and Technical Information of China (English)

    刘家阔; 顾为; 聂爱华

    2011-01-01

    炭疽是由炭疽芽孢杆菌引起的一种人畜共患烈性传染病.炭疽菌主要通过释放炭疽毒素使宿主致病.炭疽毒素包括致死毒素和水肿毒素,这两种毒素是使炭疽感染者死亡的主要因素.该文综述了抗炭疽毒素小分子药物的研究进展.%Anthrax is a severe epidemic disease caused by Bacillus anthracis, and acts mainly by releasing anthrax toxin that consists of two toxins, lethal toxin (LT) and edema toxin (ET), which are the primary factors of death. In this review the recent advances in the development of small molecule inhibitors of anthrax toxin are discussed.

  18. [Mortality in metropolitan regions].

    Science.gov (United States)

    Simoes Ccds

    1980-01-01

    Data from the 1970 census and a 1974-1975 survey carried out in Brazil by the Fundacao Instituto Brasileiro de Geografia e Estatistica are used to examine recent mortality trends in urban areas. Specifically, life expectancy in nine metropolitan areas is analyzed in relation to income, diet, and sanitary facilities in the home.

  19. Affine stochastic mortality

    NARCIS (Netherlands)

    D.F. Schrager

    2006-01-01

    We propose a new model for stochastic mortality. The model is based on the literature on affine term structure models. It satisfies three important requirements for application in practice: analytical tractibility, clear interpretation of the factors and compatibility with financial option pricing m

  20. Enhanced Early Innate and T Cell-mediated Responses in Subjects Immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909)

    OpenAIRE

    Minang, Jacob T.; Inglefield, Jon R.; Harris, Andrea M.; Lathey, Janet L.; Alleva, David G.; Sweeney, Diane L.; Hopkins, Robert J.; Lacy, Michael J.; Bernton, Edward W.

    2014-01-01

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a Phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax® (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24 to 48 hours...

  1. Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein A for removal of anthrax toxin protective antigen.

    Science.gov (United States)

    Ingavle, Ganesh C; Baillie, Les W J; Zheng, Yishan; Lis, Elzbieta K; Savina, Irina N; Howell, Carol A; Mikhalovsky, Sergey V; Sandeman, Susan R

    2015-05-01

    Polymeric cryogels are efficient carriers for the immobilization of biomolecules because of their unique macroporous structure, permeability, mechanical stability and different surface chemical functionalities. The aim of the study was to demonstrate the potential use of macroporous monolithic cryogels for biotoxin removal using anthrax toxin protective antigen (PA), the central cell-binding component of the anthrax exotoxins, and covalent immobilization of monoclonal antibodies. The affinity ligand (protein A) was chemically coupled to the reactive hydroxyl and epoxy-derivatized monolithic cryogels and the binding efficiencies of protein A, monoclonal antibodies to the cryogel column were determined. Our results show differences in the binding capacity of protein A as well as monoclonal antibodies to the cryogel adsorbents caused by ligand concentrations, physical properties and morphology of surface matrices. The cytotoxicity potential of the cryogels was determined by an in vitro viability assay using V79 lung fibroblast as a model cell and the results reveal that the cryogels are non-cytotoxic. Finally, the adsorptive capacities of PA from phosphate buffered saline (PBS) were evaluated towards a non-glycosylated, plant-derived human monoclonal antibody (PANG) and a glycosylated human monoclonal antibody (Valortim(®)), both of which were covalently attached via protein A immobilization. Optimal binding capacities of 108 and 117 mg/g of antibody to the adsorbent were observed for PANG attached poly(acrylamide-allyl glycidyl ether) [poly(AAm-AGE)] and Valortim(®) attached poly(AAm-AGE) cryogels, respectively, This indicated that glycosylation status of Valortim(®) antibody could significantly increase (8%) its binding capacity relative to the PANG antibody on poly(AAm-AGE)-protien-A column (p PBS through PANG or Valortim bound poly(AAm-AGE) cryogel were significantly (p PBS over 60 min of circulation. The high adsorption capacity towards anthrax toxin PA of the

  2. 2011年四川省炭疽个案调查%Survey of Anthrax Cases in Sichuan Province

    Institute of Scientific and Technical Information of China (English)

    李帆; 汪立茂; 吴朝学; 魏敏; 祁腾

    2013-01-01

    Objective To analyze pathogenic characteristics of anthrax of Sichuan province in 2011, and to provide scientific basis for future prevention work. Methods All cases reported from network in 2011 were statistically analyzed with respects of onset date and current addresses. Results A total of 86 anthrax cases were reported and all were skin anthrax, and the male accounted for 69. 77% , significantly more than women; the pas-toralist was the dominating occupation (72. 09% ), followed by the farmers (19. 77% ). The average age was 39. 12, and the onsets were mainly young adults. The onset peak appeared in July to September of the year, contacting, striping and eating dead animals were the main sources of infection (61. 63% ); and contacting was the main infection modus (98. 84% ). Conclusion Contacting, striping and eating dead animals has become primary means of human anthrax infections. The work of health education and livestock epidemic control should be enhanced.%目的 分析四川省2011年炭疽病例发病特征,为今后的防治工作提供依据.方法 收集整理2011年所有通过网络报告病例的个案调查表,按发病日期和现住址进行统计分析.结果 2011年全省共报告炭疽病例86例,均为皮肤型炭疽;男性占69.77%,明显多于女性;职业以牧民为主(72.09%),其次为农民(19.77%);平均年龄39.12岁,青壮年发病较多;发病高峰出现在7~9月;接触、剥食病死动物是最主要的感染来源(61.63%),接触感染是主要的感染方式(98.84%).结论 2011年四川省炭疽病例主要为青壮年男性,剥食和接触病死动物成为引起人间炭疽的感染的主要方式,应加强健康教育和畜间疫情的控制力度.

  3. The public science of Louis Pasteur: the experiment on anthrax vaccine in the popular press of the time.

    Science.gov (United States)

    Bucchi, M

    1997-01-01

    The paper focuses on Pasteur's public experimentation of the anthrax vaccine (Pouilly-le-Fort, 1881) as portrayed in the English and French popular press of the time. It is argued that this 'popular' level of representation did not merely provide additional publicity for Pasteur's ideas. Rather, the nature and meaning of the experiment itself and of the related controversy on immunisation were substantially negotiated and shaped within the public arena. The multifold consequences of this framing at the public level are explored. In particular, attention is drawn to the relationships that in such process were established with other issues debated at the same time in the arena, namely homeopathy, vivisection and vaccination.

  4. HIV and maternal mortality.

    Science.gov (United States)

    Lathrop, Eva; Jamieson, Denise J; Danel, Isabella

    2014-11-01

    The majority of the 17 million women globally that are estimated to be infected with HIV live in Sub-Saharan Africa. Worldwide, HIV-related causes contributed to 19 000-56 000 maternal deaths in 2011 (6%-20% of maternal deaths). HIV-infected pregnant women have two to 10 times the risk of dying during pregnancy and the postpartum period compared with uninfected pregnant women. Many of these deaths can be prevented with the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART. The paper summarizes what is known about HIV disease progression in pregnancy, specific causes of HIV-related maternal deaths, and the potential impact of treatment with antiretroviral therapy on maternal mortality. Recommendations are proposed for improving maternal health and decreasing maternal mortality among HIV-infected women based on existing evidence.

  5. [AIDS mortality in France].

    Science.gov (United States)

    Hatton, F; Maguin, P; Nicaud, V; Renaud, G

    1986-01-01

    A study about mortality by AIDS had been undertaken since July 1st 1983, in the Service of Information on Medical causes of Death (INSERM SC8), which is in charge of developing mortality statistics in France. From July 1st 1983 to September 30th 1985, 243 deaths due to AIDS were recorded. Only the cases where this diagnosis was clearly mentioned were selected; more than 90% were notified by hospitals and mainly by highly specialized services. The number of deaths, which was low and varied rather irregularly at the beginning, then increased by successive stages. The first year, during which a tenth of deaths was recorded every three months, was followed by a great increase, doubling, then tripling the initial numbers. Lastly, a second and sudden rise occurred during the third trimester of 1985, the trimestrial number of deaths due to AIDS reaching 80.

  6. Pelvic fractures and mortality.

    OpenAIRE

    K.H. Chong; DeCoster, T.; Osler, T.; Robinson, B.

    1997-01-01

    A retrospective study of all patients (N = 343) with pelvic fractures admitted to our trauma service was conducted to evaluate the impact of pelvic fractures on mortality. All patients sustained additional injuries with an average Injury Severity Score (ISS) of twenty. Thirty-six patients died. This group had more severe pelvic fractures as graded by the Tile classification as well as a greater number and severity of associated injuries. Six patients died as a direct result of pelvic hemorrha...

  7. Deciphering infant mortality

    Science.gov (United States)

    Berrut, Sylvie; Pouillard, Violette; Richmond, Peter; Roehner, Bertrand M.

    2016-12-01

    This paper is about infant mortality. In line with reliability theory, "infant" refers to the time interval following birth during which the mortality (or failure) rate decreases. This definition provides a systems science perspective in which birth constitutes a sudden transition falling within the field of application of the Transient Shock (TS) conjecture put forward in Richmond and Roehner (2016c). This conjecture provides predictions about the timing and shape of the death rate peak. It says that there will be a death rate spike whenever external conditions change abruptly and drastically and also predicts that after a steep rise there will be a much longer hyperbolic relaxation process. These predictions can be tested by considering living organisms for which the transient shock occurs several days after birth. Thus, for fish there are three stages: egg, yolk-sac and young adult phases. The TS conjecture predicts a mortality spike at the end of the yolk-sac phase and this timing is indeed confirmed by observation. Secondly, the hyperbolic nature of the relaxation process can be tested using very accurate Swiss statistics for postnatal death rates spanning the period from one hour immediately after birth through to age 10 years. It turns out that since the 19th century despite a significant and large reduction in infant mortality, the shape of the age-specific death rate has remained basically unchanged. Moreover the hyperbolic pattern observed for humans is also found for small primates as recorded in the archives of zoological gardens. Our overall objective is to identify a series of cases which start from simple systems and move step by step to more complex organisms. The cases discussed here we believe represent initial landmarks in this quest.

  8. Epidemiological analysis of anthrax in Gansu Province from 2005 to 2011%2005-2011年甘肃省炭疽流行病学分析

    Institute of Scientific and Technical Information of China (English)

    刘东鹏; 刘新凤; 魏孔福; 杨建军

    2012-01-01

    目的 分析甘肃省近年炭疽流行病学特征,为制定防制策略提供科学依据.方法 对甘肃2005-2011年炭疽疫情报告情况及相关资料进行回顾性分析.结果 7年来甘肃省每年均有炭疽病例发生,累计报告发病306例,发病率在0.07/10万~0.25/10万之间波动,年平均发病率为0.17/10万;具有一定的地域性特征,主要发病在牧区,甘南州发病率最高(4.88/10万);发病季节多见于夏秋季的6-9月,占总发病数的54.58%;男性(67.65%)多于女性(32.35%),年龄以青壮年为主;以皮肤型炭疽最为多见,占98.37%.结论 甘肃省仍然是我国炭疽高发省份之一;认真做好炭疽防治知识的宣传教育工作,加强相关部门间合作,及时发现并处理疫情是防治本病的重要措施.%Objective To analyze the epidemiological features of anthrax in Gansu Province, and provide scientific evidence for developing preventive and control strategies. Methods The dada of anthrax epidemic in Cansu Province from 2005 to 2011 was analyzed by using retrospective study. Results The cases of anthrax occurred in Gansu Province every year in recent seven years, and there were totally 306 cases of anthrax. The incidence of anthrax was 0. 17/105 on average, and all incidences waved between 0. 07/10 to 0. 25/10 . Major anthrax cases occurred in pastoral areas, and the highest incidence area was Gannan (4. 88/105). Anthrax was more common during June to September in summer and autumn, accounting for 54.58% of total cases. The incidence in males (67.65%) was higher than that in females (32. 35% ) , and main in youth people. Cutaneous anthrax was the most common (98. 37% ) type. Conclusion Gansu is still one of the provinces with high incidence of anthrax in China. Health education on anthrax prevention and treatment, strengthening cooperation among related departments, identifying and controlling epidemics on time are the key measures for prevention and control on anthrax.

  9. Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

    Energy Technology Data Exchange (ETDEWEB)

    Ekworomadu, MarCia T.; Poor, Catherine B.; Owens, Cedric P.; Balderas, Miriam A.; Fabian, Marian; Olson, John S.; Murphy, Frank; Balkabasi, Erol; Honsa, Erin S.; He, Chuan; Goulding, Celia W.; Maresso, Anthony W. (Baylor); (UCI); (Cornell); (Rice); (UC)

    2014-10-02

    To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 3{sub 10}-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 3{sub 10}-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with

  10. Excess Early Mortality in Schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

    2014-01-01

    Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality as ...

  11. Epidemiological Investigation of Cutaneous Anthrax Outbreak%皮肤炭疽疫情的流行病学调查

    Institute of Scientific and Technical Information of China (English)

    任丽云

    2015-01-01

    某地自6月25日~7月5日累计发生4例皮肤炭疽病例。疫情发生后,采取了隔离治疗病人为主的综合性治疗措施,控制了疫情的发展。根据患者的临床表现、流行病学调查以及患者的病原学检测结果,认为此起事件是由病死牛传播引起的皮肤炭疽疫情。按照《省突发公共卫生事件应急预案》的规定符合一般突发公共卫生事件的标准,启动Ⅳ级应急响应。%A place from June 25 - July 5 cumulative four cases of cutaneous anthrax cases have occurred. After the out-break, taking the isolation and treatment of patients based integrated treatment measures to control the development of the epidemic. According to clinical manifestations, epidemiology and etiology of the patient's test results that this incident was cutaneous anthrax epidemic caused by the spread of cattle died. In accordance with the"provincial public health emergency contingency plan" in line with the provisions of the general standard of public health emergencies, start Ⅳ level emergency response.

  12. Secretory expression and efficient purification of recombinant anthrax toxin lethal factor with full biological activity in E. coli.

    Science.gov (United States)

    Liu, Ju; Cai, Chenguang; Guo, Qiang; Zhang, Jun; Dong, Dayong; Li, Guanlin; Fu, Ling; Xu, Junjie; Chen, Wei

    2013-05-01

    Lethal factor (LF), a virulence factor of Bacillus anthracis, plays key roles in anthrax pathogenesis and host-pathogen interactions. The detailed mechanisms by which LF contributes to infection are still under investigation. While these studies require pure, homogeneous and reliable LF preparations, most methods reported for production of recombinant LF (rLF) in B. anthracis or Escherichia coli either are complicated or add extra residues to the protein. In this work, we modified our previous method by codon optimization and chromatograph workflow refinement and developed an improved strategy for efficient production of rLF from the periplasm of E. coli. We were able to obtain fully functional rLF with a purity above 95% and with a considerable yield of 5 mg/L. The preparation was characterized by SDS-PAGE, Western blot, and N-terminal sequencing, and the activity was validated by intoxication of macrophages and Fischer 344 rats. Our final product is suitable for most research involving drug development and mechanism analysis of anthrax pathogenesis.

  13. Development of a Sterne-based Complement Fixation Test to monitor the humoral response induced by anthrax vaccines

    Directory of Open Access Journals (Sweden)

    Rosanna eAdone

    2016-01-01

    Full Text Available Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals and humans depends on the prevention in livestock, principally cattle, sheep and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2– B.anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA, Lethal Factor (LF and Edema Factor (EF. The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test to detect specific antibodies induced in animals vaccinated with Sterne 34F2 . We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to identify vaccinated animals with a good sensitivity and specificity offering many benefits especially with regard to costs, standardization and reproducibility of the assay procedure.

  14. Cytolethal distending toxin B as a cell-killing component of tumor-targeted anthrax toxin fusion proteins.

    Science.gov (United States)

    Bachran, C; Hasikova, R; Leysath, C E; Sastalla, I; Zhang, Y; Fattah, R J; Liu, S; Leppla, S H

    2014-01-16

    Cytolethal distending toxin (Cdt) is produced by Gram-negative bacteria of several species. It is composed of three subunits, CdtA, CdtB, and CdtC, with CdtB being the catalytic subunit. We fused CdtB from Haemophilus ducreyi to the N-terminal 255 amino acids of Bacillus anthracis toxin lethal factor (LFn) to design a novel, potentially potent antitumor drug. As a result of this fusion, CdtB was transported into the cytosol of targeted cells via the efficient delivery mechanism of anthrax toxin. The fusion protein efficiently killed various human tumor cell lines by first inducing a complete cell cycle arrest in the G2/M phase, followed by induction of apoptosis. The fusion protein showed very low toxicity in mouse experiments and impressive antitumor effects in a Lewis Lung carcinoma model, with a 90% cure rate. This study demonstrates that efficient drug delivery by a modified anthrax toxin system combined with the enzymatic activity of CdtB has great potential as anticancer treatment and should be considered for the development of novel anticancer drugs.

  15. Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa—Chromosomal Monophyly and Broad Geographic Distribution

    Science.gov (United States)

    Mabon, Philip; Zimmermann, Fee; Lankester, Felix; Peller, Tianna; Feistner, Anna; Todd, Angelique; Herbinger, Ilka; de Nys, Hélène M.; Muyembe-Tamfun, Jean-Jacques; Karhemere, Stomy; Wittig, Roman M.; Couacy-Hymann, Emmanuel; Grunow, Roland; Calvignac-Spencer, Sébastien; Corbett, Cindi R.; Klee, Silke R.; Leendertz, Fabian H.

    2016-01-01

    Through full genome analyses of four atypical Bacillus cereus isolates, designated B. cereus biovar anthracis, we describe a distinct clade within the B. cereus group that presents with anthrax-like disease, carrying virulence plasmids similar to those of classic Bacillus anthracis. We have isolated members of this clade from different mammals (wild chimpanzees, gorillas, an elephant and goats) in West and Central Africa (Côte d’Ivoire, Cameroon, Central African Republic and Democratic Republic of Congo). The isolates shared several phenotypic features of both B. anthracis and B. cereus, but differed amongst each other in motility and their resistance or sensitivity to penicillin. They all possessed the same mutation in the regulator gene plcR, different from the one found in B. anthracis, and in addition, carry genes which enable them to produce a second capsule composed of hyaluronic acid. Our findings show the existence of a discrete clade of the B. cereus group capable of causing anthrax-like disease, found in areas of high biodiversity, which are possibly also the origin of the worldwide distributed B. anthracis. Establishing the impact of these pathogenic bacteria on threatened wildlife species will require systematic investigation. Furthermore, the consumption of wildlife found dead by the local population and presence in a domestic animal reveal potential sources of exposure to humans. PMID:27607836

  16. Development of a Sterne-Based Complement Fixation Test to Monitor the Humoral Response Induced by Anthrax Vaccines

    Science.gov (United States)

    Adone, Rosanna; Sali, Michela; Francia, Massimiliano; Iatarola, Michela; Donatiello, Adelia; Fasanella, Antonio

    2016-01-01

    Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals, and humans depend on the prevention in livestock, principally cattle, sheep, and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2–) B. anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF). The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test (CFT) to detect specific antibodies induced in animals vaccinated with Sterne 34F2. We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to correctly identify vaccinated animals. It proved to be a very sensitive and specific test. Moreover, the Sterne-based CFT offers many benefits with regard to costs, standardization and reproducibility of the assay procedure. PMID:26858700

  17. Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.

    Science.gov (United States)

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie; Hou, Lihua; Chen, Wei

    2014-02-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

  18. 一例肺炭疽死亡病例的流行病学调查分析%Epidemiological survey of death case of pulmonary anthrax

    Institute of Scientific and Technical Information of China (English)

    陈卫民; 刘丹

    2012-01-01

    2011年8月内蒙古自治区乌兰浩特市发生一起炭疽死亡病例疫情.采用流行病学调查、噬菌体裂解实验及青霉素敏感实验进行分析和诊断.共确诊6例病例,其中5例皮肤炭疽病例治疗痊愈,1例肺炭疽死亡.患者有明确的病、死畜接触史.通过对感染病畜肉的追踪销毁、接触人群的隔离检查及患者接触环境的消毒,及时有效地控制了病情的发展.%To understand the epidemiological characteristics of 1 death case of pulmonary anthrax and provide scientific evidence for developing prevention and control measures. Epidemiological survey, bacteriophage lyric test and penicillin-sensitive test were conducted. Among 6 anthrax cases diagnosed, 5 cases of cutaneous anthrax recovered after treatment, 1 cases of pulmonary anthrax died. The death case had obvious contact with sick and dead livestock. The epidemic was effectively controlled by tracing and destroying of sick livestock neat, isolation of close contacts and environment disinfection.

  19. Assessment of Neutralising Activity of Colostrum-Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1 Anthrax Lethal Toxin Cytototoxity Assay

    Science.gov (United States)

    2005-12-01

    Assessment of Neutralising Activity of Colostrum - Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1 Anthrax Lethal Toxin...activity of colostrum -derived, polyclonal, bovine antibodies. Antibodies against lethal factor and protective antigen were found to protect...APPROVED FOR PUBLIC RELEASE Assessment of Neutralising Activity of Colostrum - Derived, Polyclonal, Bovine Antibodies: Use of the J774A.1

  20. Stillbirth and Infant Mortality

    DEFF Research Database (Denmark)

    Nøhr, Ellen Aagaard

    2012-01-01

    mechanisms behind these associations remain largely unknown. Although maternal obesity is associated with a wide range of complications in the mother and neonate that may impair fetal and infant survival, the increased risk of stillbirth and infant mortality is virtually unchanged when accounting...... indicating that some of the excess risk may have a placental origin. To further understand the associations between maternal obesity and late fetal and infant death, we need better and more detailed clinical data, which is difficult to obtain on a population level given the rarity of the outcomes. The best...

  1. Cross-reactivity of anthrax and C2 toxin: protective antigen promotes the uptake of botulinum C2I toxin into human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Angelika Kronhardt

    Full Text Available Binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the AB(7/8 type of toxins. The B subunits bind both host cell receptors and the enzymatic A polypeptides to trigger their internalization and translocation into the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase (C2I and C2II binding subunits. Anthrax toxin is composed of adenylate cyclase (EF and MAPKK protease (LF enzymatic components associated to protective antigen (PA binding subunit. The binding and translocation components anthrax protective antigen (PA(63 and C2II of C2 toxin share a sequence homology of about 35%, suggesting that they might substitute for each other. Here we show by conducting in vitro measurements that PA(63 binds C2I and that C2II can bind both EF and LF. Anthrax edema factor (EF and lethal factor (LF have higher affinities to bind to channels formed by C2II than C2 toxin's C2I binds to anthrax protective antigen (PA(63. Furthermore, we could demonstrate that PA in high concentration has the ability to transport the enzymatic moiety C2I into target cells, causing actin modification and cell rounding. In contrast, C2II does not show significant capacity to promote cell intoxication by EF and LF. Together, our data unveiled the remarkable flexibility of PA in promoting C2I heterologous polypeptide translocation into cells.

  2. Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax

    Directory of Open Access Journals (Sweden)

    N Ghosh

    2015-01-01

    Full Text Available Background & objectives: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA in human cutaneous anthrax cases. Methods: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. Results: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] =0.9982; slope=0.9186; intercept = 0.1108. Interpretation & conclusions: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

  3. The genome of a Bacillus isolate causing anthrax in chimpanzees combines chromosomal properties of B. cereus with B. anthracis virulence plasmids.

    Directory of Open Access Journals (Sweden)

    Silke R Klee

    Full Text Available Anthrax is a fatal disease caused by strains of Bacillus anthracis. Members of this monophyletic species are non motile and are all characterized by the presence of four prophages and a nonsense mutation in the plcR regulator gene. Here we report the complete genome sequence of a Bacillus strain isolated from a chimpanzee that had died with clinical symptoms of anthrax. Unlike classic B. anthracis, this strain was motile and lacked the four prohages and the nonsense mutation. Four replicons were identified, a chromosome and three plasmids. Comparative genome analysis revealed that the chromosome resembles those of non-B. anthracis members of the Bacillus cereus group, whereas two plasmids were identical to the anthrax virulence plasmids pXO1 and pXO2. The function of the newly discovered third plasmid with a length of 14 kbp is unknown. A detailed comparison of genomic loci encoding key features confirmed a higher similarity to B. thuringiensis serovar konkukian strain 97-27 and B. cereus E33L than to B. anthracis strains. For the first time we describe the sequence of an anthrax causing bacterium possessing both anthrax plasmids that apparently does not belong to the monophyletic group of all so far known B. anthracis strains and that differs in important diagnostic features. The data suggest that this bacterium has evolved from a B. cereus strain independently from the classic B. anthracis strains and established a B. anthracis lifestyle. Therefore we suggest to designate this isolate as "B. cereus variety (var. anthracis".

  4. Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

    Science.gov (United States)

    Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

    2016-01-06

    Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors.

  5. 白云机场可疑炭疽事件和对航空旅行的影响%Suspicious Anthrax Events and Its Affect to the Air Travel in the Baiyuan International Airport, Guangzhou, China

    Institute of Scientific and Technical Information of China (English)

    胡龙飞

    2002-01-01

    @@ Objective: The anthrax panic first occurred in the United States in Oct., 2001 was rapidly spread worldwide within a very short period. Like other international airport in the world, there were the same suspicious events occurred in the Baiyun International Airport, Guangzhou during the period.This paper aimed to discuss the factors affecting the air travel and the effective measures to lessen the panic in the related population when this kind of suspicious anthrax event occurred.

  6. Maternal mortality due to trauma.

    Science.gov (United States)

    Romero, Vivian Carolina; Pearlman, Mark

    2012-02-01

    Maternal mortality is an important indicator of adequacy of health care in our society. Improvements in the obstetric care system as well as advances in technology have contributed to reduction in maternal mortality rates. Trauma complicates up to 7% of all pregnancies and has emerged as the leading cause of maternal mortality, becoming a significant concern for the public health system. Maternal mortality secondary to trauma can often be prevented by coordinated medical care, but it is essential that caregivers recognize the unique situation of providing simultaneous care to 2 patients who have a complex physiologic relationship. Optimal management of the pregnant trauma victim requires a multidisciplinary team, where the obstetrician plays a central role. This review focuses on the incidence of maternal mortality due to trauma, the mechanisms involved in traumatic injury, the important anatomic and physiologic changes that may predispose to mortality due to trauma, and finally, preventive strategies that may decrease the incidence of traumatic maternal death.

  7. PROGRESS ON THE ANTHRAX TOXIN AND THE CELLULAR CLONE RECEPTOR FOR ANTHRAX TOXIN%炭疽毒素及其克隆受体的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘承宜; 李艳玲; 段锐; 李燕; 蔡雄伟; 黄平

    2002-01-01

    综述炭疽毒素研究的最新进展.炭疽毒素由3种蛋白组成:致死因子(Lethal factor,LF),水肿因子(edema factor,EF)和保护性抗原(protective antigen,PA).本文主要讲述了炭疽毒素的关键致病因子--致死因子(LF)的结构和功能,炭疽毒素受体(anthrax toxin receptor,ATR)的结构及其特征性功能基团,介绍了通过基因互补对ATR进行克隆的方法,并讨论了ATR和ATR的cDNA克隆在炭疽治疗的可能应用.

  8. Gender difference in child mortality.

    Science.gov (United States)

    Ahmed, F A

    1990-12-01

    1976 census data and data on births to 8788 ever married women from the 1980 Egyptian Fertility Survey were analyzed to determine if son preference was responsible for higher mortality among girls than among boys and what factors were associated with this higher mortality. During 0-3 years, boys were more likely to die than females. For example, the overall male-female sex ratio for the 1st year was 118:100. At ages 5, 10, 15, and 2 0, however, girls were more likely to die. The sex rations for these years were 98, 95, 93, and 91. In fact, the excess mortality among illiterate mothers accounted for most of the overall excess mortality. As mother's educational level rose, the excess mortality of girls fell, so that by university level boys experienced excess mortality (130, 111, 112, 105). Less educated mothers breast fed sons longer and waited more months after birth of a son to have another child indicating son preference, but these factors did not necessarily contribute to excess mortality. The major cause of female excess mortality in Egypt was that boys received favored treatment of digestive and respiratory illnesses as indicated by accessibility to a pharmacy (p.01). Norms/traditions and religion played a significant role in excess mortality. The effect of norms/traditions was greater than religion, however. Mother's current and past employment strongly contributed to reducing girls' mortality levels (p.01). These results indicated that Egypt should strive to increase the educational level of females and work opportunities for women to reduce female child mortality. Further, it should work to improve women's status which in turn will reduce norms/traditions that encourage son preference and higher mortality level for girls.

  9. Adult mortality in preindustrial Quebec

    Directory of Open Access Journals (Sweden)

    Claudine Lacroix - - - Bertrand Desjardins

    2012-01-01

    Full Text Available This paper presents the main results of a detailed study on adult mortality in French Canadians born before 1750 and having married inthe colony of New France. Using data from parish registers, mortality is studied using abridged life tables, with staggered entries according to age at first marriage. Survival tables and log-Rank tests are used to support the results. Three features were selected for the study of differential mortality: gender, type of residence area (urban or rural, and cohort. The mortality of French Canadians is compared to that of their French contemporaries.

  10. Classification differences and maternal mortality

    DEFF Research Database (Denmark)

    Salanave, B; Bouvier-Colle, M H; Varnoux, N;

    1999-01-01

    of experts into obstetric or non-obstetric causes. An ICD-9 code (International Classification of Diseases) was attributed to each case. These were compared to the codes given in each country. Correction indices were calculated, giving new estimates of maternal mortality rates. SUBJECTS: There were....... This change was substantial in three countries (P maternal mortality rate for participating countries was 7.7 per...... and consequently affect maternal mortality rates. Differences in classification of death must be taken into account when comparing maternal mortality rates, as well as differences in obstetric care, underreporting of maternal deaths and other factors such as the age distribution of mothers....

  11. 吸入性炭疽的防治措施%Imbedibility anthrax preventing and controlling measure

    Institute of Scientific and Technical Information of China (English)

    任晓波; 期滟淋

    2010-01-01

    炭疽(anthrax)是由炭疽芽胞肝菌(Bacillus anthracis)引起的人畜共患疾病.通过皮肤、呼吸道和消化道感染.吸入性炭疽即是炭疽孢子自呼吸道吸入而引起的肺炭疽,是炭疽病的一种临床类型,平时较少见,但在敌人使用生物恐怖袭击时,则是最常见最危险的疾病之一.因而,在过去、现在和未来生物恐怖袭击中,均具有重要意义[1].

  12. Prediction of protein-peptide interactions: application of the XPairIt API to anthrax lethal factor and substrates

    Science.gov (United States)

    Hurley, Margaret M.; Sellers, Michael S.

    2013-05-01

    As software and methodology develop, key aspects of molecular interactions such as detailed energetics and flexibility are continuously better represented in docking simulations. In the latest iteration of the XPairIt API and Docking Protocol, we perform a blind dock of a peptide into the cleavage site of the Anthrax lethal factor (LF) metalloprotein. Molecular structures are prepared from RCSB:1JKY and we demonstrate a reasonably accurate docked peptide through analysis of protein motion and, using NCI Plot, visualize and characterize the forces leading to binding. We compare our docked structure to the 1JKY crystal structure and the more recent 1PWV structure, and discuss both captured and overlooked interactions. Our results offer a more detailed look at secondary contact and show that both van der Waals and electrostatic interactions from peptide residues further from the enzyme's catalytic site are significant.

  13. Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009–2010

    Science.gov (United States)

    Cui, Xizhong; Nolen, Leisha D.; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P.; Boyer, Anne E.; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A.

    2017-01-01

    We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009–2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0–5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6–11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak. PMID:27983504

  14. Eoidemic of Anthrax in Sichuan Province, 2004 -2009%2004-2009年四川省炭疽疫情分析

    Institute of Scientific and Technical Information of China (English)

    汪立茂; 李帆; 祝小平; 魏敏; 吴建林

    2011-01-01

    目的 分析四川省炭疽疫情动态及流行因素,为制定防制策略提供科学依据.方法 根据疫情资料及暴发疫情现场流调报告,对疫情资料进行病学统计分析.结果 2004 - 2009年四川省共报告炭疽病例712例,发病呈现小的上升趋势,流行表现形式以常年散发伴局部地区小暴发为主,具有一定的地域性特征,主要发病在牧区和半农半牧地区,阿坝州较高(9.33/10万)、高于甘孜州(1.96/10万)和凉山州(0.46/10万),发病季节多见于夏秋季的7~9月(55.90%),发病年龄以农牧民中的青壮年为主,男性多于女性.结论 四川省炭疽疫情呈小上升趋势,应加大健康教育力度,加强对畜间的免疫和监管,卫生、畜牧部门相互配合,及时发现和处理疫情.%Objective To analyze the epidemic situation and factors of anthrax in Sichuan province from 2004 to 2009, and provide scientific evidence for developing preventive and control strategies. Methods The data of anthrax epidemic in Sichuan province from 2004 to 2009 was analyzed by using epidemiological methods. Results There were 712 reported anthrax cases in Sichuan province from 2004 to 2009. The major epidemic form of anthrax was sporadic with outbreaks in some areas. The incidence in Aba was higher (9. 33/105) than in Ganzi (1. 96/105) and Iiangshan prefecture (0. 46/105). Anthrax was more common during June to September in summer and autumn, accounting for 55. 90% , and main in youth among peasants and stock raisers. The incidence in males was higher than that in females. Conclusion Anthrax epidemic in Sichuan province presents a minor upward trend. Health education for peasants and stock raisers, immunication and supervision among domestic animals should be strengthened. Relative departments should cooperate with each other to discover and deal with the epidemic in time.

  15. Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

    Directory of Open Access Journals (Sweden)

    Matthew A Crawford

    Full Text Available Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.

  16. Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Steven L.; Lesperance, Ann M.; Upton, Jaki F.

    2010-02-01

    On October 9, 2008, federal, state and local policy makers, emergency managers, and medical and public health officials convened in Seattle, Washington, for a workshop on Addressing the Federal-State-Local Interface Issues During a Catastrophic Event Such as an Anthrax Attack. The day-long symposium was aimed at generating a dialogue about recovery and restoration through a discussion of the associated challenges that impact entire communities, including people, infrastructure, and critical systems. The Principal Federal Official (PFO) provided an overview of the role of the PFO in a catastrophic event. A high-level summary of an anthrax scenario was presented. The remainder of the day was focused on interactive discussions among federal, state and local emergency management experts in the areas of: • Decision-making, prioritization, and command and control • Public health/medical services • Community resiliency and continuity of government. Key topics and issues that resulted from discussions included: • Local representation in the Joint Field Office (JFO) • JFO transition to the Long-Term Recovery Office • Process for prioritization of needs • Process for regional coordination • Prioritization - process and federal/military intervention • Allocation of limited resources • Re-entry decision and consistency • Importance of maintaining a healthy hospital system • Need for a process to establish a consensus on when it is safe to re-enter. This needs to be across all jurisdictions including the military. • Insurance coverage for both private businesses and individuals • Interaction between the government and industry. The symposium was sponsored by the Interagency Biological Restoration Demonstration, a collaborative regional program jointly funded by the U.S. Department of Homeland Security and the U.S. Department of Defense. To aid the program’s efforts and inform the development of blueprint for recovery from a biological incident

  17. Indonesia lowers infant mortality.

    Science.gov (United States)

    Bain, S

    1991-11-01

    Indonesia's success in reaching World Health Organization (WHO) universal immunization coverage standards is described as the result of a strong national program with timely, targeted donor support. USAID/Indonesia's Expanded Program for Immunization (EPI) and other USAID bilateral cooperation helped the government of Indonesia in its goal to immunize children against diphtheria, pertussis, tetanus, polio, tuberculosis, and measles by age 1. The initial project was to identify target areas and deliver vaccines against the diseases, strengthen the national immunization organization and infrastructure, and develop the Ministry of Health's capacity to conduct studies and development activities. This EPI project spanned the period 1979-90, and set the stage for continued expansion of Indonesia's immunization program to comply with the full international schedule and range of immunizations of 3 DPT, 3 polio, 1 BCG, and 1 measles inoculation. The number of immunization sites has increased from 55 to include over 5,000 health centers in all provinces, with additional services provided by visiting vaccinators and nurses in most of the 215,000 community-supported integrated health posts. While other contributory factors were at play, program success is at least partially responsible for the 1990 infant mortality rate of 58/1,000 live births compared to 72/1,000 in 1985. Strong national leadership, dedicated health workers and volunteers, and cooperation and funding from UNICEF, the World Bank, Rotary International, and WHO also played crucially positive roles in improving immunization practice in Indonesia.

  18. PREDICTION OF AEROSOL HAZARDS ARISING FROM THE OPENING OF AN ANTHRAX-TAINTED LETTER IN AN OPEN OFFICE ENVIRONMENT USING COMPUTATIONAL FLUID DYNAMICS

    Directory of Open Access Journals (Sweden)

    FUE-SANG LIEN

    2010-09-01

    Full Text Available Early experimental work, conducted at Defence R&D Canada–Suffield, measured and characterized the personal and environmental contamination associated with simulated anthrax-tainted letters under a number of different scenarios in order to obtain a better understanding of the physical and biological processes for detecting, assessing, and formulating potential mitigation strategies for managing the risks associated with opening an anthrax-tainted letter. These experimental investigations have been extended in the present study to simulate numerically the contamination from the opening of anthrax-tainted letters in an open office environment using computational fluid dynamics (CFD. A quantity of 0.1 g of Bacillus atropheus (formerly referred to as Bacillus subtilis var globigii (BG spores in dry powder form, which was used here as a surrogate species for Bacillus anthracis (anthrax, was released from an opened letter in the experiment. The accuracy of the model for prediction of the spatial distribution of BG spores in the office from the opened letter is assessed qualitatively (and to the extent possible, quantitatively by detailed comparison with measured BG concentrations obtained under a number of different scenarios, some involving people moving within the office. The observed discrepancy between the numerical predictions and experimental measurements of concentration was probably the result of a number of physical processes which were not accounted for in the numerical simulation. These include air flow leakage from cracks and crevices of the building shell; the dispersion of BG spores in the Heating, Ventilation, and Air Conditioning (HVAC system; and, the effect of deposition and re-suspension of BG spores from various surfaces in the office environment.

  19. Analysing the spatial patterns of livestock anthrax in Kazakhstan in relation to environmental factors: a comparison of local (Gi*) and morphology cluster statistics.

    Science.gov (United States)

    Kracalik, Ian T; Blackburn, Jason K; Lukhnova, Larisa; Pazilov, Yerlan; Hugh-Jones, Martin E; Aikimbayev, Alim

    2012-11-01

    We compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle) and small (sheep and goats) domestic ruminants across Kazakhstan. The Getis-Ord (Gi*) statistic and a multidirectional optimal ecotope algorithm (AMOEBA) were compared using 1st, 2nd and 3rd order Rook contiguity matrices. Multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the AMOEBA and Gi* tests. A logistic regression was used to define a risk surface for anthrax outbreaks and to compare agreement between clustering methodologies. Tests revealed differences in the spatial distribution of clusters as well as the total number of clusters in large ruminants for AMOEBA (n = 149) and for small ruminants (n = 9). In contrast, Gi* revealed fewer large ruminant clusters (n = 122) and more small ruminant clusters (n = 61). Significant environmental differences were found between groups using the Kruskall-Wallis and Mann-Whitney U tests. Logistic regression was used to model the presence/absence of anthrax outbreaks and define a risk surface for large ruminants to compare with cluster analyses. The model predicted 32.2% of the landscape as high risk. Approximately 75% of AMOEBA clusters corresponded to predicted high risk, compared with ~64% of Gi* clusters. In general, AMOEBA predicted more irregularly shaped clusters of outbreaks in both livestock groups, while Gi* tended to predict larger, circular clusters. Here we provide an evaluation of both tests and a discussion of the use of each to detect environmental conditions associated with anthrax outbreak clusters in domestic livestock. These findings illustrate important differences in spatial statistical methods for defining local clusters and highlight the importance of selecting appropriate levels of data aggregation.

  20. Analysing the spatial patterns of livestock anthrax in Kazakhstan in relation to environmental factors: a comparison of local (Gi* and morphology cluster statistics

    Directory of Open Access Journals (Sweden)

    Ian T. Kracalik

    2012-11-01

    Full Text Available We compared a local clustering and a cluster morphology statistic using anthrax outbreaks in large (cattle and small (sheep and goats domestic ruminants across Kazakhstan. The Getis-Ord (Gi* statistic and a multidirectional optimal ecotope algorithm (AMOEBA were compared using 1st, 2nd and 3rd order Rook contiguity matrices. Multivariate statistical tests were used to evaluate the environmental signatures between clusters and non-clusters from the AMOEBA and Gi* tests. A logistic regression was used to define a risk surface for anthrax outbreaks and to compare agreement between clustering methodologies. Tests revealed differences in the spatial distribution of clusters as well as the total number of clusters in large ruminants for AMOEBA (n = 149 and for small ruminants (n = 9. In contrast, Gi* revealed fewer large ruminant clusters (n = 122 and more small ruminant clusters (n = 61. Significant environmental differences were found between groups using the Kruskall-Wallis and Mann- Whitney U tests. Logistic regression was used to model the presence/absence of anthrax outbreaks and define a risk surface for large ruminants to compare with cluster analyses. The model predicted 32.2% of the landscape as high risk. Approximately 75% of AMOEBA clusters corresponded to predicted high risk, compared with ~64% of Gi* clusters. In general, AMOEBA predicted more irregularly shaped clusters of outbreaks in both livestock groups, while Gi* tended to predict larger, circular clusters. Here we provide an evaluation of both tests and a discussion of the use of each to detect environmental conditions associated with anthrax outbreak clusters in domestic livestock. These findings illustrate important differences in spatial statistical methods for defining local clusters and highlight the importance of selecting appropriate levels of data aggregation.

  1. Inhalational anthrax (Ames aerosol) in naive and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    OpenAIRE

    Bradford eGutting; Tonya L Nichols; Channel, Stephen R.; Gearhart, Jeffery M.; Andrews, George A.; Berger, Alan E.; Mackie, Ryan S.; Brent J Watson; Taft, Sarah C.; Overheim, Katie A.; Robert L Sherwood

    2012-01-01

    There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (>100LD50) of Bacillus anthracis (Ames) spores immediately following exposure through 36 hours. The primary goal of collecting the data w...

  2. [Asthma mortality trends in Mexico].

    Science.gov (United States)

    Salas Ramírez, M; Segura Méndez, N H; Martínez-Cairo Cueto, S

    1994-04-01

    The objective of this cross-sectional study was to estimate mortality and morbidity from asthma in Mexico by federative entity (state) of residence, age, and sex during the period between 1960 and 1988. Statistics published by the National Institute of Statistics, Geography, and Information Science were reviewed, as were vital statistics and information from other sources. Data were selected on mortality, hospital admissions, and outpatient visits, as well as population by federative entity, age, and sex. Mortality and morbidity rates were adjusted for age using the direct method. From 1960 to 1987, mortality decreased for both sexes. The groups with the highest asthma mortality were those under 4 years of age and those over 50. From 1960 to the present, the state with the highest mortality was Tlaxcala. Hospitalizations increased from 10 to 140 per 100,000 population for the country as a whole. When both outpatient visits and hospitalizations were considered, the morbidity rates rose from 180 to 203.4 per 100,000 between 1960 and 1970. In 1970, hospital morbidity was higher among males than females. From 1960 up to the 1990s, the highest rates of hospitalization and outpatient visits were registered among those under 4 and those over 60. The states with the highest asthma hospitalization rates were Morelos, Baja California Sur, Nuevo León, Durango, and Tamaulipas. It is concluded that asthma mortality in Mexico is showing a downward trend, while morbidity is increasing considerably, especially among adolescents.

  3. Trends in child mortality in India.

    Science.gov (United States)

    Behl, A S

    2013-01-08

    To assess Indias recent trends in child mortality rates and disparities and identify ways to reduce child mortality and wealth-related health disparities, we analyzed three years of data from Indias National Family Health Survey related to child mortality. Nationally, declines in average child mortality were statistically significant, but declines in inequality were not. Urban areas had lower child mortality rates than rural areas but higher inequalities. Interstate differences in child mortality rates were significant, with rates in the highest-mortality states four to six times higher than in the lowest-mortality states. However, child mortality in most states declined.

  4. The law of mortality revisited: interspecies comparisons of mortality.

    Science.gov (United States)

    Olshansky, S J

    2010-01-01

    In 1825 the British actuary Benjamin Gompertz believed he had discovered a consistency in the timing of death in people that was so important that he labelled his observation a 'law of mortality'. To Gompertz, this 'law' was equivalent in importance to Newton's law of gravity because he believed it would be observed in all living things. Gompertz's quest for the 'law' eventually failed, as did similar efforts by other scientists in the 19th and most of the 20th century. However, the search for the law of mortality was successfully resolved in 1996 when my colleagues and I discovered that the only way to 'see' Gompertz's law expressed as common age patterns of death across species was to partition total mortality into its intrinsic and extrinsic components, and examine mortality schedules on a uniform time scale. Scientists had been unable to reveal the law of mortality in the past not only because they could not partition total mortality, but also because of the previous anthropocentric perspective that forced some scientists to view duration of life along a single time scale - one based on human measurements of chronological time. The law of mortality is relevant today not only because it links the epidemiology of disease, ageing and death across species, but because it creates a window into the future for those who study disease epidemiology in animals that now live long enough in protected environments to experience the biological consequences of ageing. In this paper I summarize the historical search for the law of mortality, explain why the solution could only be found by linking two seemingly unconnected scientific disciplines (evolution biology and actuarial/demographics), explain why age patterns of disease and death in humans may be used to understand and predict disease epidemiology in other species, and describe how a new scientific discipline has arisen in the modern era as a result of this research.

  5. 炭疽毒素及其致病机制的研究进展%Progress in research on anthrax toxins and their pathogenesis

    Institute of Scientific and Technical Information of China (English)

    武利涛; 魏建春; 海荣

    2012-01-01

    Anthrax toxins include edema toxin (ET) and lethal toxin (LT) which are critical pathogenic factors produced by Bacillus anthracis. ET is composed of protective antigen (PA) and edema factor (EF) , while a mixture of PA and lethal factor (LF) form LT. This review summaries the progress in research on anthrax toxins and their pathogenesis from the aspects of the gene, structure and biological activity and the scientific significance of the research in the prevention and control of anthrax.%炭疽毒素包括水肿毒素( edema toxin,ET)和致死毒素(lethal toxin,LT),是炭疽芽胞杆菌产生的重要致病因子.ET由保护性抗原(protective antigen,PA)和水肿因子(edema factor,EF)组成,LT由PA和致死因子(lethal factor,LF)组成.本文从基因、结构及生物学活性等方面概述了炭疽毒素各组分在炭疽芽胞杆菌致病机制中的作用方式,并阐述了其对炭疽防治措施的科学指导意义.

  6. Clinical features and nursing of cutaneous anthrax patients%皮肤炭疽患者的临床特征与护理

    Institute of Scientific and Technical Information of China (English)

    阴嘉微

    2014-01-01

    Objective To explore proper nursing interventions for cutaneous anthrax patients. Methods According to clinic features of the patients with cutaneous anthrax, sterilized insulation, individual protection, proper disposal of patients’wounded part, excreta and applications, as well as mental counseling and health education, were used to observe whether these interventions could enhance patients’recovery and prevent hospital infection. Results By using the above-mentioned methods all 13 cutaneous anthrax patients recovered quickly and no hospital infection incidents took place. Conclusion Proper nursing interventions can prevent hospital infection and promote recovery.%目的:探索适合皮肤炭疽患者的护理措施。方法针对皮肤炭疽的临床特点,应用消毒隔离、个人防护,对患者患处、排泄物和应用物处理,并经心理疏导、健康教育,观察是否可促进患者康复及杜绝医院内感染。结果13例皮肤炭疽患者经上述处理后未发生院内交叉感染,全部痊愈出院。结论适宜的护理措施可防止皮肤炭疽患者医院内感染,促进疾病的康复。

  7. Stressful social relations and mortality

    DEFF Research Database (Denmark)

    Lund, Rikke; Christensen, Ulla; Nilsson, Charlotte Juul

    2014-01-01

    BACKGROUND: Few studies have examined the relationship between stressful social relations in private life and all-cause mortality. OBJECTIVE: To evaluate the association between stressful social relations (with partner, children, other family, friends and neighbours, respectively) and all......-cause mortality in a large population-based study of middle-aged men and women. Further, to investigate the possible modification of this association by labour force participation and gender. METHODS: We used baseline data (2000) from The Danish Longitudinal Study on Work, Unemployment and Health, including 9875...... men and women aged 36-52 years, linked to the Danish Cause of Death Registry for information on all-cause mortality until 31 December 2011. Associations between stressful social relations with partner, children, other family, friends and neighbours, respectively, and all-cause mortality were examined...

  8. CDC WONDER: Mortality - Infant Deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Infant Deaths (from Linked Birth / Infant Death Records) online databases on CDC WONDER provide counts and rates for deaths of children under 1 year...

  9. A retrospective study on the epidemiology of anthrax, foot and mouth disease, haemorrhagic septicaemia, peste des petits ruminants and rabies in Bangladesh, 2010-2012.

    Directory of Open Access Journals (Sweden)

    Shankar P Mondal

    Full Text Available Anthrax, foot and mouth disease (FMD, haemorrhagic septicaemia (HS, peste des petits ruminants (PPR and rabies are considered to be endemic in Bangladesh. This retrospective study was conducted to understand the geographic and seasonal distribution of these major infectious diseases in livestock based on data collected through passive surveillance from 1 January 2010 to 31 December 2012. Data analysis for this period revealed 5,937 cases of anthrax, 300,333 of FMD, 13,436 of HS, 247,783 of PPR and 14,085 cases of dog bite/rabies. While diseases were reported in almost every district of the country, the highest frequency of occurrence corresponded to the susceptible livestock population in the respective districts. There was no significant difference in the disease occurrences between districts bordering India/Myanmar and non-border districts (p>0.05. Significantly higher (p<0.01 numbers of anthrax (84.5%, FMD (88.3%, HS (84.9% and dog bite/rabies (64.3% cases were reported in cattle than any other species. PPR cases were reported mostly (94.8% in goats with only isolated cases (5.2% in sheep. The diseases occur throughout the year with peak numbers reported during June through September and lowest during December through April, with significant differences (p<0.01 between the months. The annual usages of vaccines for anthrax, FMD, HS and PPR were only 7.31%, 0.61%, 0.84% and 11.59% of the susceptible livestock population, respectively. Prophylactic vaccination against rabies was 21.16% of cases. There were significant differences (p<0.01 in the administration of anthrax, FMD and HS vaccines between border and non-border districts, but not PPR or rabies vaccines. We recommend that surveillance and reporting of these diseases need to be improved throughout the country. Furthermore, all suspected clinical cases should be confirmed by laboratory examination. The findings of this study can be used in the formulation of more effective disease

  10. Maternal mortality in Bijapur district

    Directory of Open Access Journals (Sweden)

    Vidya A. Thobbi

    2015-04-01

    Full Text Available Objectives: The objectives of this study is to evaluate the incidence of maternal deaths, causes responsible for maternal mortality, direct and indirect factors, and various preventable methods to reduce maternal mortality rate. Background: 95% of maternal deaths occur in Asia and Africa. The need for undertaking this study is to know the maternal mortality rate, analyze the causes and preventable factors of death occurring in the district of Bijapur, Karnataka, India. Methodology: It is a study of 2years from the Records of District Health Office and Institutions on maternal mortality from June 2011 to May 2013 in Bijapur. Results: In two years there were fifty eight maternal deaths and seventy nine thousand five hundred and sixty six live births, hence maternal mortality ratio was seventy three per lakh live births. Eighty two percent of maternal deaths occurred in families who belonged to Below Poverty Line. Prevalence of anemia in pregnancy was 79.3%. Severe anemia (Hemoglobin <7g% seen in 5.1% was the most common indirect cause of death. Forty three percent of the deaths occurred at private setups. Hemorrhage, Septicemia and Preeclampsia & Eclampsia were responsible for 44.82%, 15.51% and 6.89% respectively. Conclusion: Majority of the maternal deaths are preventable if these four delays are avoided: a Delay in identifying the problem. b Delay in seeking care. c Delay in reaching the referral institute. d Delay in getting treatment on reaching the referral institute.

  11. Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine containing aluminum hydroxide and glycopyranoside lipid A adjuvants.

    Science.gov (United States)

    Hassett, Kimberly J; Vance, David J; Jain, Nishant K; Sahni, Neha; Rabia, Lilia A; Cousins, Megan C; Joshi, Sangeeta; Volkin, David B; Middaugh, C Russell; Mantis, Nicholas J; Carpenter, John F; Randolph, Theodore W

    2015-02-01

    During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose.

  12. Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen.

    Science.gov (United States)

    Lynch, Heather E; Stewart, Shelley M; Kepler, Thomas B; Sempowski, Gregory D; Alam, S Munir

    2014-02-01

    Establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. Quantitative assays that allow monitoring of affinity maturation and duration of antibody responses can provide useful information regarding the efficacy of vaccines and adjuvants. Using an anthrax protective antigen (rPA) and alum model antigen/adjuvant system, we describe a methodology for monitoring antigen-specific serum antibody concentration and avidity by surface plasmon resonance during primary and secondary immune responses. Our analyses showed that following a priming dose in mice, rPA-specific antibody concentration and avidity increases over time and reaches a maximal response in about six weeks, but gradually declines in the absence of antigenic boost. Germinal center reactions were observed early with maximal development achieved during the primary response, which coincided with peak antibody avidity responses to primary immunization. Boosting with antigen resulted in a rapid increase in rPA-specific antibody concentration and five-fold increase in avidity, which was not dependent on sustained GC development. The described methodology couples surface plasmon resonance-based plasma avidity measurements with germinal center analysis and provides a novel way to monitor humoral responses that can play a role in facilitating vaccine and adjuvant development.

  13. Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

    Science.gov (United States)

    Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

    2013-10-17

    We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  14. NMR conformational properties of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling

    Energy Technology Data Exchange (ETDEWEB)

    Vourtsis, Dionysios J.; Chasapis, Christos T.; Pairas, George [Department of Pharmacy, University of Patras, GR-26504 Patras (Greece); Bentrop, Detlef [Institute of Physiology II, University of Freiburg, D-79104 Freiburg (Germany); Spyroulias, Georgios A., E-mail: G.A.Spyroulias@upatras.gr [Department of Pharmacy, University of Patras, GR-26504 Patras (Greece)

    2014-07-18

    Highlights: • A polypeptide, N-ALF{sub 233}, was overexpressed in E. coli and successfully isolated. • We produced {sup 2}H/{sup 15}N/{sup 13}C labeled protein samples. • Amino acid selective approaches were applied. • We acquired several heteronuclear NMR spectra, to complete the backbone assignment. • Prediction of the secondary structure was performed. - Abstract: NMR-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution NMR spectra and their subsequent analysis. Especially for bigger proteins (>20 kDa) selective labeling is a frequently used means of sequence-specific assignment. In this work we present the successful overexpression of a polypeptide of 233 residues, corresponding to the structured part of the N-terminal domain of Anthrax Lethal Factor, using Escherichia coli expression system. The polypeptide was subsequently isolated in pure, soluble form and analyzed structurally by solution NMR spectroscopy. Due to the non-satisfying quality and resolution of the spectra of this 27 kDa protein, an almost complete backbone assignment became feasible only by the combination of uniform and novel amino acid-selective labeling schemes. Moreover, amino acid-type selective triple-resonance NMR experiments proved to be very helpful.

  15. LAMP using a disposable pocket warmer for anthrax detection, a highly mobile and reliable method for anti-bioterrorism.

    Science.gov (United States)

    Hatano, Ben; Maki, Takayuki; Obara, Takeyuki; Fukumoto, Hitomi; Hagisawa, Kohsuke; Matsushita, Yoshitaro; Okutani, Akiko; Bazartseren, Boldbaastar; Inoue, Satoshi; Sata, Tetsutaro; Katano, Harutaka

    2010-01-01

    A quick, reliable detection system is necessary to deal with bioterrorism. Loop-mediated isothermal amplification (LAMP) is a DNA amplification method that can amplify specific DNA fragments in isothermal conditions. We developed a new highly mobile and practical LAMP anthrax detection system that uses a disposable pocket warmer without the need for electricity (pocket-warmer LAMP). In our tests, the detection limit of the pocket-warmer LAMP was 1,000 copies of Bacillus anthracis pag and capB gene fragments per tube. The pocket-warmer LAMP also detected B. anthracis genes from DNA extracted from 0.1 volume of a B. anthracis colony. The lower detection limit of the pocket-warmer LAMP was not significantly different from that of a conventional LAMP using a heat block, and was not changed under cold (4 degrees C) or warm (37 degrees C) conditions in a Styrofoam box. The pocket-warmer LAMP could be useful against bioterrorism, and as a sensitive, reliable detection tool in areas with undependable electricity infrastructures.

  16. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening from other...... factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between...

  17. Electrocardiographic Predictors of Cardiovascular Mortality

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1, prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes, spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria.

  18. Mortality rates among wild chimpanzees.

    Science.gov (United States)

    Hill, K; Boesch, C; Goodall, J; Pusey, A; Williams, J; Wrangham, R

    2001-05-01

    In order to compare evolved human and chimpanzees' life histories we present a synthetic life table for free-living chimpanzees, derived from data collected in five study populations (Gombe, Taï, Kibale, Mahale, Bossou). The combined data from all populations represent 3711 chimpanzee years at risk and 278 deaths. Males show higher mortality than females and data suggest some inter-site variation in mortality. Despite this variation, however, wild chimpanzees generally have a life expectancy at birth of less than 15 years and mean adult lifespan (after sexual maturity) is only about 15 years. This is considerably lower survival than that reported for chimpanzees in zoos or captive breeding colonies, or that measured among modern human hunter-gatherers. The low mortality rate of human foragers relative to chimpanzees in the early adult years may partially explain why humans have evolved to senesce later than chimpanzees, and have a longer juvenile period.

  19. Targeted interventions and infant mortality.

    Science.gov (United States)

    Lovel, H

    1989-01-01

    The main causes of infant mortality in 71% of the cases are diarrhea, measles, acute respiratory infection, and neonatal tetanus. A UN child survival strategy includes growth monitoring, oral rehydration, breast feeding, immunization, fertility, food and female literacy (GOBI-FFF). Previous research has shown a correlation between low levels of infant mortality and high levels of female literacy. Educated women are more likely to delay marriage, and childbearing. Child mortality is much higher for those born to women under 20 years old and also much higher for those born within 1 or 2 after the previous birth. Maternal mortality is also higher for mothers under 20 and with closely spaced births of 3 or more children. The majority of adults in developing countries have knowledge of family planning but teen pregnancy is a concern. Better nutrition during pregnancy would decrease infant deaths. Growth monitoring is another way to reduce infant mortality and morbidity. The difficulties are in the reluctance to adapt programs to local traditional methods of growth monitoring and going to direct recording scales. Immunization is estimated to have prevented over 3 million deaths from measles, tetanus, whooping cough and polio in 1984 alone. In spite of progress, only 50% of children in developing countries are immunized against diphtheria, pertussis, polio, and tetanus by the age of 1 year. these activities must be integrated into primary health care and community development projects to make better contact with people needing this service. oral rehydration therapy not only reduces mortality from diarrhea but can reduce morbidity by reducing the duration of the illness and by increasing the weight gain. Breast feeding has been shown in many studies to reduce the risk of deaths of infants. The promotion of breast feeding includes the issues of maternity leave, job security, and child care at the work place.

  20. Mortality in adult congenital heart disease

    NARCIS (Netherlands)

    Verheugt, Carianne L.; Uiterwaal, Cuno S. P. M.; van der Velde, Enno T.; Meijboom, Folkert J.; Pieper, Petronella G.; van Dijk, Arie P. J.; Vliegen, Hubert W.; Grobbee, Diederick E.; Mulder, Barbara J. M.

    2010-01-01

    Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality pre

  1. Is cancer mortality increasing in France?

    OpenAIRE

    Hill, C.; Jan, P; Doyon, F

    2001-01-01

    Long-term trends in cancer mortality are reported by site. Overall, cancer mortality has been decreasing in France since 1987 in the male population and since 1968 in the female population. Improvement in treatments and diagnosis should lead to persistently declining mortality rates, unless the tobacco epidemic reverses the trend in female mortality. © 2001 Cancer Research Campaign http://www.bjcancer.com

  2. America's Infant-Mortality Puzzle.

    Science.gov (United States)

    Eberstadt, Nicholas

    1991-01-01

    Conventional explanations attributing the high infant mortality rate in United States to the prevalence of poverty and lack of adequate health care do not tell the whole story. Contributions of parental behavior, lifestyles, and public health care availability versus utilization must be examined in determining public policies to address the…

  3. Infant Mortality: The Shared Concern.

    Science.gov (United States)

    Heagarty, Margaret C.

    1990-01-01

    Addresses the causes for and implications of infant mortality. Besides the more immediate causes such as disease, nutrition, and lifestyle, there are the additional hurdles of government bureaucracy, lack of funds, and institutional attitudes that block access to prenatal care. Suggests structural solutions, including a consistent, individual,…

  4. Testosterone deficiency and cardiovascular mortality

    Institute of Scientific and Technical Information of China (English)

    Abraham Morgentaler

    2015-01-01

    New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T‑treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T‑deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.

  5. Child mortality in rural India

    NARCIS (Netherlands)

    B. van der Klaauw (Bas); L. Wang (Lihong)

    2011-01-01

    textabstractThis paper focuses on infant and child mortality in rural areas of India. We construct a flexible duration model, which allows for frailty at multiple levels and interactions between the child's age and individual, socioeconomic, and environmental characteristics. The model is estimated

  6. Excess mortality following hip fracture

    DEFF Research Database (Denmark)

    Abrahamsen, B; van Staa, T; Ariely, R;

    2009-01-01

    Summary This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlig...

  7. Peptic ulcers: mortality and hospitalization.

    Science.gov (United States)

    Riley, R

    1991-01-01

    This study analyzes data on peptic ulcer disease based on deaths for 1951-1988 and hospital separations for 1969-1988. The source of the data are mortality and morbidity statistics provided to Statistics Canada by the provinces. The age-standardized mortality rates (ASMR) for peptic ulcer disease decreased from 1951 to 1988 by 69.4% for men (8.5 to 2.6 per 100,000 population), and 31.8% for women (2.2 to 1.5). Separation rates from hospitals during 1969-1988 for peptic ulcer disease also decreased by 59.8% for men (242.7 to 97.6 per 100,000 population) and 35.6% for women (103.2 to 66.5). Age-specific rates for both mortality and hospital separations increased with age. Epidemiological studies indicate that the incidence of peptic ulcer disease is declining in the general population. The downward trends in mortality and hospitalization rates for peptic ulcer disease reflect this change in incidence, but additional factors probably contribute as well to this decline. Male rates for both mortality and hospital separations were much higher than female rates at the beginning of the study period; but toward the end, the gap between the sexes narrowed considerably, mainly because the male rates declined substantially while the female rates decline moderately. The slower decline in the rates for women may be related to such factors as the increasing labour force participation among women and the slower decline in the population of female smokers.

  8. Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers.

    Science.gov (United States)

    Rynkiewicz, Dianna; Rathkopf, Melinda; Sim, Iain; Waytes, A Thomas; Hopkins, Robert J; Giri, Lallan; DeMuria, Deborah; Ransom, Janet; Quinn, James; Nabors, Gary S; Nielsen, Carl J

    2011-08-26

    Immunization with BioThrax(®) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2) 1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis.

  9. Microevolution of Anthrax from a Young Ancestor (M.A.Y.A. Suggests a Soil-Borne Life Cycle of Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Peter Braun

    Full Text Available During an anthrax outbreak at the Pollino National Park (Basilicata, Italy in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA and next generation Whole Genome Sequencing (WGS. PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis.

  10. Inhalational anthrax (Ames aerosol in naive and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    Directory of Open Access Journals (Sweden)

    Bradford eGutting

    2012-06-01

    Full Text Available There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (>100LD50 of Bacillus anthracis (Ames spores immediately following exposure through 36 hours. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA or were sham-vaccinated, and were then exposed in pairs (1 sham and 1 AVA so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated, while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits. Between 4-5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL fluid. After 6 and 36 hours, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN 12 hours post exposure and in the circulation at 24 hours, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 hours at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed

  11. Microevolution of Anthrax from a Young Ancestor (M.A.Y.A.) Suggests a Soil-Borne Life Cycle of Bacillus anthracis.

    Science.gov (United States)

    Braun, Peter; Grass, Gregor; Aceti, Angela; Serrecchia, Luigina; Affuso, Alessia; Marino, Leonardo; Grimaldi, Stefania; Pagano, Stefania; Hanczaruk, Matthias; Georgi, Enrico; Northoff, Bernd; Schöler, Anne; Schloter, Michael; Antwerpen, Markus; Fasanella, Antonio

    2015-01-01

    During an anthrax outbreak at the Pollino National Park (Basilicata, Italy) in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA) and next generation Whole Genome Sequencing (WGS). PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis.

  12. Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA vaccine to prevent anthrax in adults.

    Directory of Open Access Journals (Sweden)

    Bruce K Brown

    Full Text Available BACKGROUND: The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29 was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. CONCLUSIONS/SIGNIFICANCE: The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00057525.

  13. Metrology and visualized analysis of anthrax research literature%国内外炭疽研究文献计量与可视化分析

    Institute of Scientific and Technical Information of China (English)

    刘伟; 吴曙霞; 盛立; 陈婷; 张筱菁; 刁天喜

    2015-01-01

    目的:探索炭疽研究领域的发展情况、研究趋势及动态前沿,以期为我国炭疽研究提供信息支持,为生物反恐提供策略思路。方法基于Web of Knowledge文献数据平台( SCI),综合应用Pajek、VOSviewer、Bibexcel软件;基于中国科学引文数据库( CSCD)数据平台,使用Excel软件。结果通过文献计量可视化分析显示,炭疽研究主要分布在欧美国家,美国炭疽研究整体实力最强,军事医学科学院、中国科学院等机构为我国炭疽主要科研力量,但我国与国际相关研究机构尚存在一定差距。结论我国应加强炭疽研究,提高整体研究实力,为应对可能发生的生物恐怖事件提供必要的保障。%Objective To explore the development of the anthrax research field in order to provide information and strategies for anti-bioterrorism in China.Methods Pajek, Vosviewer, Bibexcel running on Web of Knowledge platform, and Excel running on CSCD platform were used.Results According to the results of anthrax literature metrology,the USA is by far the leader in research while the Academy of Military Medical Sciences, Chinese Academy of Sciences and other in-stitutions are our main anthrax research institutions in China, but there is a gap between China and international research institutions.Conclusion We should strengthen anthrax research, improve the overall research strength, and provide the necessary protection to respond to potential bioterrorism incidents.

  14. Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Crown, Devorah; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; Sankaran, Banumathi; Lehrer, Axel; Wong, Teri; Johns, Lisa; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2012-03-15

    Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.

  15. Growth characteristics of Bacillus anthracis compared to other Bacillus spp. on the selective nutrient media Anthrax Blood Agar and Cereus Ident Agar.

    Science.gov (United States)

    Tomaso, Herbert; Bartling, Carsten; Al Dahouk, Sascha; Hagen, Ralf M; Scholz, Holger C; Beyer, Wolfgang; Neubauer, Heinrich

    2006-01-01

    Anthrax Blood Agar (ABA) and Cereus Ident Agar (CEI) were evaluated as selective growth media for the isolation of Bacillus anthracis using 92 B. anthracis and 132 other Bacillus strains from 30 species. The positive predictive values for the identification of B. anthracis on ABA, CEI, and the combination of both were 72%, 71%, and 90%, respectively. Thus, less than 10% of all species were misidentified using both nutrient media. Species which might be misidentified as B. anthracis were B. cereus, B. mycoides, and B. thuringiensis. Particularly, 30% of B. weihenstephanensis strains were misidentified as B. anthracis.

  16. Inhalational anthrax (Ames aerosol) in naïve and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia.

    Science.gov (United States)

    Gutting, Bradford W; Nichols, Tonya L; Channel, Stephen R; Gearhart, Jeffery M; Andrews, George A; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Taft, Sarah C; Overheim, Katie A; Sherwood, Robert L

    2012-01-01

    There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (> 100 LD(50)) of Bacillus anthracis (Ames) spores immediately following exposure through 36 h. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA) or were sham-vaccinated, and were then exposed in pairs (one sham and one AVA) so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated), while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits). Between 4-5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL) fluid. After 6 and 36 h, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN) 12 h post-exposure and in the circulation at 24 h, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 h at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed small numbers of CFU in

  17. Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.

    Directory of Open Access Journals (Sweden)

    Joseph Chavarría-Smith

    Full Text Available Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1 protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR or AIM2-like receptor (ALR protein families. Certain NLRs and ALRs have been shown to function as direct receptors for specific microbial ligands, such as flagellin or DNA, but the molecular mechanism responsible for activation of most NLRs is still poorly understood. Here we determine the mechanism of activation of the NLRP1B inflammasome in mice. NLRP1B, and its ortholog in rats, is activated by the lethal factor (LF protease that is a key virulence factor secreted by Bacillus anthracis, the causative agent of anthrax. LF was recently shown to cleave mouse and rat NLRP1 directly. However, it is unclear if cleavage is sufficient for NLRP1 activation. Indeed, other LF-induced cellular events have been suggested to play a role in NLRP1B activation. Surprisingly, we show that direct cleavage of NLRP1B is sufficient to induce inflammasome activation in the absence of LF. Our results therefore rule out the need for other LF-dependent cellular effects in activation of NLRP1B. We therefore propose that NLRP1 functions primarily as a sensor of protease activity and thus could conceivably detect a broader spectrum of pathogens than just B. anthracis. By adding proteolytic cleavage to the previously established ligand-receptor mechanism of NLR activation, our results illustrate the remarkable flexibility with which the NLR architecture can be deployed for the purpose of pathogen-detection and host defense.

  18. Protective Antigen-Specific Memory B Cells Persist Years after Anthrax Vaccination and Correlate with Humoral Immunity

    Directory of Open Access Journals (Sweden)

    Lori Garman

    2014-08-01

    Full Text Available Anthrax Vaccine Adsorbed (AVA generates short-lived protective antigen (PA specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs from individuals vaccinated ≥3 times with AVA (n = 50 were collected early (3–6 months, n = 27 or late after their last vaccination (2–5 years, n = 23, pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs. PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57% and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03 and toxin neutralization (r = 0.52, p = 0.003 early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001 and late post vaccination (r = 0.71, p < 0.0001. These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.

  19. Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children.

    NARCIS (Netherlands)

    Wijngaard, C.C. van den; Asten, L. van; Koopmans, M.P.G.; Pelt, W. van; Nagelkerke, N.J.D.; Wielders, C.C.H.; Lier, A. van; Hoek, W. van der; Meijer, A.; Donker, G.A.; Dijkstra, F.; Harmsen, C.; Sande, M.A.B. van der; Kretzschmar, M.

    2012-01-01

    Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. F

  20. Mortality level, trends and differentials in Malawi.

    Science.gov (United States)

    Palamuleni, M E

    1994-01-01

    "This article examines the levels, and trends and differentials in mortality in Malawi.... The study has shown that (i) the level of mortality is very high in Malawi; (ii) mortality has declined during the period under review; (iii) there was reduction in the rate of mortality decline in the seventies; and (iv) [there are] interesting differences in mortality in terms of rural-urban localities, regions and age-sex differentials. The observed levels, trends and differentials in mortality are however consistent with the level of social and economic development in the country."

  1. Physical Inactivity and Mortality Risk

    Directory of Open Access Journals (Sweden)

    Peter Kokkinos

    2011-01-01

    Full Text Available In recent years a plethora of epidemiologic evidence accumulated supports a strong, independent and inverse, association between physical activity and the fitness status of an individual and mortality in apparently healthy individuals and diseased populations. These health benefits are realized at relatively low fitness levels and increase with higher physical activity patterns or fitness status in a dose-response fashion. The risk reduction is at least in part attributed to the favorable effect of exercise or physical activity on the cardiovascular risk factors, namely, blood pressure, diabetes mellitus and obesity. In this review, we examine evidence from epidemiologic and interventional studies in support of the association between exercise and physical activity and health. In addition, we present the exercise effects on the aforementioned risk factors. Finally, we include select dietary approaches and their impact on risk factors and overall mortality risk.

  2. Educational differences in cardiovascular mortality

    DEFF Research Database (Denmark)

    Kjøllesdal, M. K. R.; Ariansen, I.; Mortensen, L. H.;

    2016-01-01

    Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked...... with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants (n=271,310). Data were available on CVD risk factors, including...... weight, height, blood pressure, total cholesterol and smoking. Results: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98–3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors...

  3. Testosterone Therapy and Mortality Risk

    Science.gov (United States)

    Eisenberg, Michael L.; Li, Shufeng; Herder, Danielle; Lamb, Dolores J.; Lipshultz, Larry I.

    2014-01-01

    INTRODUCTION Recent data suggests and increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date there are no long term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine if TT altered a man’s risk of all cause mortality. METHODS We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine morality. RESULTS Of the 509 men who met inclusion criteria, 284 were on testosterone therapy and 225 did not use testosterone. Age (mean 54 years) and follow up time (mean 10 years) were similar for both groups. In all, 19 men died—10 (4.4%) of the men not on TT and 9 (3.2%) of the men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (HR 1.0, 95% CI 0.39 – 2.57, p=1.0). CONCLUSIONS There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy. PMID:25078049

  4. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    Science.gov (United States)

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.

  5. Mortality and reduced growth hormone secretion

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Christiansen, Jens; Laursen, Torben

    2007-01-01

    BACKGROUND: Data regarding the mortality rates of patients with growth hormone deficiency (GHD), whether or not treated with growth hormone (GH), are limited, but an increased mortality rate among hypopituitary patients compared with the general population has been documented. Cardiovascular...

  6. Mortality hazard rates and life expectancy

    NARCIS (Netherlands)

    J.S. Cramer; R. Kaas

    2013-01-01

    We consider the relation between mortality hazards and life expectancy for men and women in the Netherlands and in England. Halving the lifetime mortality hazards increases life expectancy at birth by only 9%.

  7. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

  8. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

  9. CDC WONDER: Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979. Data...

  10. Mortality versus Morbidity in the Demographic Transition

    OpenAIRE

    Aksan, Anna-Maria; Chakraborty, Shankha

    2014-01-01

    The link between the mortality and epidemiological transitions is used to identify the effect of the former on the fertility transition: a mortality transition that is not accompanied by improving morbidity causes slower demographic and economic change. In a model where children may die from infectious disease, childhood health affects human capital and noninfectious-disease-related adult mortality. When child mortality falls from lower prevalence, as it did in western Europe, labor productiv...

  11. 炭疽毒素受体结构和功能研究进展%Progress in Structure and Function of Anthrax Toxin Receptors

    Institute of Scientific and Technical Information of China (English)

    张连成; 高丽华; 郗永义; 邵勇; 贾康杰; 胡显文; 陈惠鹏

    2013-01-01

    肿瘤血管内皮标志物8(TEMS)和毛细血管形态发生蛋白2(CMG2)是已知的两个炭疽毒素受体,它们的主要功能是当炭疽杆菌侵染细胞时介导炭疽毒素进入宿主细胞.这两个受体都是涉及到细胞外基质动态平衡的I型跨膜蛋白,并且都因为它们在血管生成或血管内皮细胞中表达增强而被发现.有研究发现TEM8能够调节内皮细胞迁移和血管形成,而CMG2则在内皮细胞增殖过程中起重要作用.进一步的研究显示它们与整联蛋白同源性较高,但它们确切的生理功能和作用机制尚不明确.本文中,主要讨论这两种蛋白的结构和它们作为炭疽毒素受体介导炭疽毒素进入细胞的分子机制,然后我们简单探讨一下TEM8在靶向肿瘤血管内皮细胞的抗血管生成和抗肿瘤疗法方面的研究进展,最后我们展望了下一步炭疽毒素受体研究的热点-它们的配体及生理功能研究.%Tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2) are the two anthrax toxin receptors,which function as mediating anthrax toxin entry into host cells when Bacillus anthracis infected cells.These two receptors are the type Ⅰ transmembrane proteins related to the dynamic equilibrium of the extracellular matrix,and they were originally identified as a gene upregulated during angiogenesis.Some studies had found that TEM8 was able to regulate endothelial cell migration and angiogenesis,while CMG2 played an important role in the process of endothelial cell proliferation.Further studies had shown that they shares interesting similarities with integrins,however their exact physiological function and mechanism is unclear.In this article,we mainly discuss the structures of these two proteins and their function and molecular mechanism as anthrax toxin receptor mediating anthrax toxin into cells,and then we briefly explore the progress of TEM8 in anti-angiogenesis and anti-tumor therapy research

  12. Neonatal tetanus mortality in coastal Kenya

    DEFF Research Database (Denmark)

    Bjerregaard, P; Steinglass, R; Mutie, D M

    1993-01-01

    In a house-to-house survey in Kilifi District, Kenya, mothers of 2556 liveborn children were interviewed about neonatal mortality, especially from neonatal tetanus (NNT). The crude birth rate was 60.5 per 1000 population, the neonatal mortality rate 21.1 and the NNT mortality rate 3.1 per 1000 li...

  13. High mortality in the Thule cohort

    DEFF Research Database (Denmark)

    Juel, K

    1994-01-01

    The objective was to study mortality in the Thule cohort in order to clarify whether it is a selected population and to ascertain the possibility of misinterpretation when national mortality rates are used as reference in the analysis of occupational mortality....

  14. Mortality in adult congenital heart disease

    NARCIS (Netherlands)

    C.L. Verheugt (Carianne); C.S.P.M. Uiterwaal (Cuno); E.T. van der Velde (Enno); F.J. Meijboom (Folkert); P.G. Pieper (Petronella); A.P.J. van Dijk (Arie); H.W. Vliegen (Hubert); D.E. Grobbee (Diederick); B.J.M. Mulder (Barbara)

    2010-01-01

    textabstractAimsMortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear.Methods and resultsThe Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regressio

  15. Advance Report of Final Mortality Statistics, 1985.

    Science.gov (United States)

    Monthly Vital Statistics Report, 1987

    1987-01-01

    This document presents mortality statistics for 1985 for the entire United States. Data analysis and discussion of these factors is included: death and death rates; death rates by age, sex, and race; expectation of life at birth and at specified ages; causes of death; infant mortality; and maternal mortality. Highlights reported include: (1) the…

  16. 进口皮毛集中加工地炭疽污染情况调查%Investigation of Anthrax Contamination at Imported Raw Hides and Wool Centralized Processing Place

    Institute of Scientific and Technical Information of China (English)

    顾志军; 朱磊; 沈炜; 沈涛

    2015-01-01

    随着我国生皮、羊毛进口量的逐年增加,国外炭疽疫情随皮毛传入我国的风险也在不断加大。为掌握炭疽随进口皮毛传入的情况,采集进口皮毛集中加工地区最有可能感染炭疽的土壤、水和从业人员血清样本进行检测。结果显示,土壤样本和水样均呈阴性;从业人员血清样本阳性率为23.9%,显著高于普通人群的阳性率(1.6%),表明进口皮毛加工从业人员存在感染炭疽的可能。本文针对上述情况提出了防控炭疽的建议。%While the import volume of raw hides and wool increased year by year in China,the risk of anthrax spread-ing into China is increasing. To grasp the introduction of anthrax with imported raw hides,the samples of soil,water and personal serum of the workers on raw hides and wool processing places with high risk of anthrax contamination were collected and tested. The results showed all soil samples and water samples were negative,and the positive rate of serum samples from workers was 23.9% which was significantly higher than the general population(1.6%). It indicated that it was possible for the workers who processed imported raw hide and wool to be infected with anthrax. Based on the above situation,some prevention and control suggestions of anthrax were proposed.

  17. Endogenous fertility, mortality and growth.

    Science.gov (United States)

    Blackburn, K; Cipriani, G P

    1998-01-01

    This paper presents a model that illustrates the joint determination of population and development. "Economic and demographic outcomes are determined jointly in a choice-theoretic model of fertility, mortality and capital accumulation.... In addition to choosing savings and births, parents may reduce (infant) deaths by incurring expenditures on health-care which is also provided by the government. A generalised production technology accounts for long-run endogenous growth with short-run transitional dynamics. The analysis yields testable time series and cross-section implications which accord with the empirical evidence on the relationship between demography and development."

  18. Spatial patterns of mortality in Bangladesh.

    Science.gov (United States)

    Sharif, A H; Huq, S M; Mesbah-us-Saleheen

    1993-05-01

    This paper depicts the spatial patterns of mortality of the administrative upazilas of Bangladesh. Due to the absence of adequate data on mortality rates from across the country, the mortality rates of the upazilas are calculated from the age sex structure of the population of the respective upazilas employing the standardized mortality rates of divisional headquarters. Crude death rates are used to determine spatial patterns of mortality in Bangladesh. The patterns portray strong regional differences. Such differentiation is accounted for by traditional differences in demographic and socio-economic factors. Also, regression analysis is used to assist in explaining spatial variations.

  19. Phenomenological theory of mortality and aginge

    Science.gov (United States)

    Azbel', Mark Ya.

    There are many theories of mortality, but no consensus even on the basic problem: is it genetically determined? In a general case, the problem is mathematically unsolvable. Yet, in the case of mortality, a physical approach yields its universal law. The law predicts, e.g., that mortality and senescence may decrease with age. Experiments verify it. I suggest experiments, which are supposed to produce genetic Methuselas, who live, e.g., over 20 η ( η is the mean life span), but whose biological age is less than η/2. If the universal mortality law is convincingly proven, it may lead to a quantitative model and theory of mortality and aging.

  20. Migrant mortality from diabetes mellitus across Europe

    DEFF Research Database (Denmark)

    Vandenheede, Hadewijch; Deboosere, Patrick; Stirbu, Irina

    2012-01-01

    The first objective of this study was to determine and quantify variations in diabetes mortality by migrant status in different European countries. The second objective was to investigate the hypothesis that diabetes mortality is higher in migrant groups for whom the country of residence (COR......) is more affluent than the country of birth (COB). We obtained mortality data from 7 European countries. To assess migrant diabetes mortality, we used direct standardization and Poisson regression. First, migrant mortality was estimated for each country separately. Then, we merged the data from all...... mortality registers. Subsequently, to examine the second hypothesis, we introduced gross domestic product (GDP) per capita of COB in the models, as an indicator of socio-economic circumstances. The overall pattern shows higher diabetes mortality in migrant populations compared to local-born populations...

  1. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

    Science.gov (United States)

    Minang, Jacob T; Inglefield, Jon R; Harris, Andrea M; Lathey, Janet L; Alleva, David G; Sweeney, Diane L; Hopkins, Robert J; Lacy, Michael J; Bernton, Edward W

    2014-11-28

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity.

  2. Epidemiology of early neonatal mortality.

    Science.gov (United States)

    Tyagi, N K; Bharambe, M S; Garg, B S; Mathur, J S; Goswami, K

    1994-01-01

    During 1981-1991 at a rural teaching hospital (Kasturba Hospital) of Mahatma Gandhi Institute of Medical Sciences in Sevagram, Wardha, India, 454 of 13,939 newborns died during the early neonatal period for an early neonatal mortality rate (ENMR) of 33.7/1000 live births. The ENMR for boys was not significantly different from that for girls (36.1 vs. 28.6). Community medicine specialists analyzed data on these early neonatal deaths to examine distribution of early neonatal mortality, especially its relationship with prematurity, low birth weight, birth order, and by sex. They calculated average percent deaths (APD) per hour to examine the dynamics in early neonatal mortality. The mean age at death was lower among newborns of birth order greater than 2 than those of birth order less than 2 (23.47 vs. 26.85 hours; p 0.001). ENMR was higher for newborns of birth order greater than 2 than those of birth order less than 2 (41.74% vs. 27.35%; P 0.001). The mean age at death increased as gestation increased (10.34 for 28 weeks; 24.27 for 28-33 weeks, 31.53 for 33-37 weeks, and 34.43 for 37 weeks; p 0.001). ENMR decreased as gestation increased (850 for 28 weeks; 375 for 28-33 weeks, 147.02 for 33-37 weeks, and 8.77 for 37 weeks; p 0.001). The mean age at death increased as birth weight increased for newborns weighing less than 1500 gms through 2000-2500 gms (23.36-37.13 hours; p 0.001). It was lowest among those weighing more 3000 gms (11.55 gms). ENMR fell as birth weight increased (614.33 for 1500 gms, 116.19 for 1500-2000 gms, 19.38 for 2000-2500 gms, 10.99 for 2500-3000 gms, and 5.41 for 3000 gms; p 0.001). The APD/hour for the first hour of life was 3.74% for a relative risk of 12.9. It decreased steadily as the hours of life increased (3.08% for 1-6 hours, 1.19% for 6-24 hours, 0.67% for 24-72 hours, and 0.29% for 72-168 hours). Knowledge of time of likely death can help providers know where they need to focus their attention to prevent early neonatal deaths.

  3. QT-Interval Duration and Mortality Rate

    Science.gov (United States)

    Zhang, Yiyi; Post, Wendy S.; Dalal, Darshan; Blasco-Colmenares, Elena; Tomaselli, Gordon F.; Guallar, Eliseo

    2012-01-01

    Background Extreme prolongation or reduction of the QT interval predisposes patients to malignant ventricular arrhythmias and sudden cardiac death, but the association of variations in the QT interval within a reference range with mortality end points in the general population is unclear. Methods We included 7828 men and women from the Third National Health and Nutrition Examination Survey. Baseline QT interval was measured via standard 12-lead electrocardiographic readings. Mortality end points were assessed through December 31, 2006 (2291 deaths). Results After an average follow-up of 13.7 years, the association between QT interval and mortality end points was U-shaped. The multivariate-adjusted hazard ratios comparing participants at or above the 95th percentile of age-, sex-, race-, and R-R interval–corrected QT interval (≥439 milliseconds) with participants in the middle quintile (401 to <410 milliseconds) were 2.03 (95% confidence interval, 1.46-2.81) for total mortality, 2.55 (1.59-4.09) for mortality due to cardiovascular disease (CVD), 1.63 (0.96-2.75) for mortality due to coronary heart disease, and 1.65 (1.16-2.35) for non-CVD mortality. The corresponding hazard ratios comparing participants with a corrected QT interval below the fifth percentile (<377 milliseconds) with those in the middle quintile were 1.39 (95% confidence interval, 1.02-1.88) for total mortality, 1.35 (0.77-2.36) for CVD mortality, 1.02 (0.44-2.38) for coronary heart disease mortality, and 1.42 (0.97-2.08) for non-CVD mortality. Increased mortality also was observed with less extreme deviations of QT-interval duration. Similar, albeit weaker, associations also were observed with Bazett-corrected QT intervals. Conclusion Shortened and prolonged QT-interval durations, even within a reference range, are associated with increased mortality risk in the general population. PMID:22025428

  4. Epidemiology of 84 anthrax outbreak cases: a systematic review of its related literature%84个炭疽暴发案例流行病学调查文献系统评价

    Institute of Scientific and Technical Information of China (English)

    许汝福; 沈渝菊; 林辉; 李亚斐; 向颖; 许斌; 张耀; 黄国荣

    2011-01-01

    Objective To provide the evidence for prevention and control of anthrax by studying the epidemiological characteristics of anthrax outbreak cases and analyzing the causes of anthrax infection in China. Methods Papers on epidemiology of 84 anthrax outbreak cases retrieved from Chinese Biomedical Literature Database and Chinese Science and Technology Journals Database were systematically reviewed. Results The 84 anthrax outbreak cases occurred in rural or pastoral areas. Of the 990 anthrax patients with a male to female ratio of 4.2∶1, 970 were cured and 20 died, 87.2% aged 15-60 years, 92.4% were farmers and herdsmen, 79.5% were located in West and South China, 87. 8% occurred in May to September. The median shortest incubation time was 2 days, the median longest incubation time was 8 days, the median diagnosis time of the first patient was 4 days, and 98.3% of the patients contacted with the affected or died animals or their meat. The relative risk was significantly higher for slaughters than for those who ate the meat (RR =55.47, 95%CI = 26.03 -118.21, P <0.000 01). The median epidemic control time for the 77 cases was 10 days. Conclusion Anthrax outbreak usually occurs in rural or pastoral areas. Young adults and farmers are at a high risk to infect with anthrax. Slaughtering affected or died animals or contacting their meat is the main cause of anthrax infection.%目的 探讨国内炭疽暴发案例流行病学特征,分析感染原因,为炭疽防控提供依据.方法 检索电子数据库中符合纳入标准的84个炭疽暴发案例流行病学调查文献资料进行系统评价.结果 84个炭疽暴发案例均发生在农村或牧区,涉及患者990例,治愈970例,死亡20例,男女比为4.2:1,15 ~60岁占87.2%,农牧民占92.4%,西北、西南和华南地区占79.5%,5~9月份占87.8%;最短潜伏期中位数2d,最长潜伏期中位数8d;首发病例诊断时间中位数4d;病畜、病死畜肉接触患者占98.3

  5. Progress on the Anthrax Toxin and Its Receptor%炭疽毒素及其细胞受体的研究进展

    Institute of Scientific and Technical Information of China (English)

    李艳玲; 刘承宜

    2002-01-01

    炭疽毒素由3种蛋白组成:保护性抗原(protective antigen,PA)、致死因子(lethal factor,LF)和水肿因子(edema factor,EF).综述炭疽毒素研究的最新进展.主要介绍炭疽毒素的关键致病因子--LF的结构与功能,炭疽毒素膜转运成分PA的结构及其受体(anthrax toxin receptor,ATR)和其cDNA克隆的结构,并讨论了在炭疽的治疗、预防和毒素在肿瘤治疗中的可能应用.

  6. Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

    Science.gov (United States)

    Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

    2015-08-26

    The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy.

  7. 炭疽受体CMG2-Fc融合蛋白在CHO细胞中的表达、纯化与鉴定%Expression,Purification and Identification of Anthrax Receptor CMG2-Fc Fusion Protein in CHO Cell

    Institute of Scientific and Technical Information of China (English)

    郗永义; 胥照平; 高丽华; 邵勇; 胡显文; 陈惠鹏

    2011-01-01

    目的:构建炭疽受体CMG2和人IgG1 Fc片段融合基因载体,转染CHO细胞并通过毒素中和试验检测CMG2-Fc拮抗炭疽毒素(PA+LF)的能力.方法:将含有CMG2胞外区1-217AA片度基因和人IgG1的Fc片段基因共同连接入pcDNA3.1载体转染CHO细胞并筛选高表达CMG2-Fc的CHO细胞系,通过小鼠RAW264.7巨噬细胞保护试验检测 CMG2-Fc拮抗炭疽毒素的能力.结果:获得了表达CMG2-Fc的细胞株,毒素中和实验显示该蛋白可以有效抑制炭疽毒素引起的细胞损伤.结论:CMG2-Fc能够保护小鼠巨噬细胞免受炭疽毒素攻击,提示其可以作为抗毒素治疗炭疽感染.%Objective: To construct fusion gene vector of anthrax receptor CMG2 and human IgG1 Fc fragent, transfect CHO cell and to testify the inhibit ability of CMG2-Fc on anthrax toxin (PA and LF) by toxin neutralization assay.Methods: An expression vector including CMG2 (1-225AA) gene and Fc fragment of human immunoglobulin G (IgG) were constructed, and CHO cell line with higher CMG2-Fc expression were got.The effect of CMG2-Fc on inhibiting anthrax toxin was detected by mouse macrophage protection assay.Result: The CHO cell line expressing CMG2-Fc protein were got, and toxin neutralization assay showed that CMG2-Fc could protect mouse RAW264.7 macrophage cell against anthrax toxins.Conclusion: CMG2-Fc can protect mouse macrophage against anthrax toxin challenge, which indicated that it maybe used as drugs against anthrax in future.

  8. 252Cf放射性同位素中子源辐照杀灭炭疽杆菌的理论研究%THEORY STUDY ON GERMICIDAL EFFICACY OF ANTHRAX SPORES BY RADIOISOTOPE Cf- 252 NEUTRON SOURCE

    Institute of Scientific and Technical Information of China (English)

    刘滨; 徐佳梁; 王凯; 胡文超

    2012-01-01

    目的 研究252Cf放射性同位素中子源辐照杀菌的可能性.方法 通过MCNP模拟计算方法,推算其所使用的模型,计算出252Cf中子辐射杀灭炭疽杆菌芽孢的辐照剂量和辐照时间.结果 经MCNP理论模拟研究,建立了MCNP模拟252Cf中子源产生的中子辐射消毒的模型,推演出使用石蜡作为反射材料可取得最好的结果.计算出用252Cf中子辐射杀灭炭疽杆菌芽孢的辐照剂量为1000 Gy,辐照时间为18 min.结论 利用252Cf中子辐射杀灭炭疽杆菌芽孢具有实际应用的可能性.%Objective To study the gerraicidal possibility of anthrax spores by radioisotope Cf - 252 neutron source. Method MCNP simulation calculation method was used to build the suitable model, calculate the radiation dose and radi-ation time required to sterilize the anthrax spores by the radioisotope Cf - 252 neutron source. Results The model was build to sterilize the anthrax spores by the radioisotope Cf - 252 neutron source. Simulation results showed that using paraffin as the reflecting materials in the model was the most effective in sterilization of the anthrax spores. The radiation dose calculated by the model was 1 000 Gy required to sterilize the anthrax spore by the radioisotope Cf - 252 neutron source, and the radiation time was about 18 min. Conclusion It is an effective and economic method to sterilize the anthrax spores by the radioisotope Cf - 252 neutron source in practical applications.

  9. The injury mortality burden in Guinea

    OpenAIRE

    Mamady Keita; Yao Hongyan; Zhang Xujun; Xiang Huiyun; Tan Hongzhuan; Hu Guoqing

    2012-01-01

    Abstract Background The injury mortality burden of Guinea has been rarely addressed. The paper aimed to report patterns of injury mortality burden in Guinea. Methods We retrieved the mortality data from the Guinean Annual Health Statistics Report 2007. The information about underlying cause of deaths was collected based on Guinean hospital discharge data, Hospital Mortuary and City Council Mortuary data. The causes of death are coded in the 9th International Classification of Diseases (ICD-9)...

  10. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Science.gov (United States)

    Ascough, Stephanie; Ingram, Rebecca J; Chu, Karen K; Reynolds, Catherine J; Musson, Julie A; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J; Gallagher, Theresa B; Dyson, Hugh; Williamson, E Diane; Robinson, John H; Maillere, Bernard; Boyton, Rosemary J; Altmann, Daniel M

    2014-05-01

    Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  11. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2014-05-01

    Full Text Available Bacillus anthracis produces a binary toxin composed of protective antigen (PA and one of two subunits, lethal factor (LF or edema factor (EF. Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  12. Simultaneous immunization of cattle with foot-and-mouth disease (FMD and live anthrax vaccines do not interfere with FMD booster responses

    Directory of Open Access Journals (Sweden)

    Myrian Trotta

    2015-01-01

    Full Text Available Foot-and-mouth disease (FMD vaccination in Argentina is compulsory for most of the cattle population and conducted by certified veterinarians. This organized campaign may facilitate the controlled application of other vaccines against endemic diseases, provided immune responses against FMD are not hindered. There is no published information on the interference of immunity against FMD vaccines when applied together with a live bacterial vaccine. In this study we evaluated if the simultaneous application of a Bacillus anthracis live vaccine with a commercial tetravalent oil-based FMD vaccine (FMD-vac used in Argentina, modifies the antibody booster responses against FMD virus (FMDV in cattle. Two groups of 16 heifers with comparable liquid phase blocking ELISA (LPBE titers were immunized with the FMD-vac alone or simultaneously with a commercial attenuated bovine anthrax Sterne strain vaccine (ABV. Serum samples were obtained at 0, 25, 60 and 90 days post vaccination (dpv and specific antibodies against two FMDV vaccine strains were assessed by LPBE, avidity and IgG-isotype ELISAs. Bovines immunized with FMD-vac or FMDV-V + ABV responded with a boost in the LPBE antibody titers and avidity at 25 dpv, and remained within similar levels up to the end of the study. Animals vaccinated with FMD-vac + ABV had significantly higher LPBE titers at 25 dpv, compared to those immunized with FMD-vac alone; which was due to an increase in IgG2 titers. Overall, antibody titers elicited in both groups were similar and followed comparable kinetics over time. We conclude that the simultaneous application of a live anthrax vaccine with the current FMD tetravalent vaccine used in Argentina in cattle previously immunized against FMD, did not counteract the serological response induced by FMD vaccination.

  13. Consistent Predictions of Future Forest Mortality

    Science.gov (United States)

    McDowell, N. G.

    2014-12-01

    We examined empirical and model based estimates of current and future forest mortality of conifers in the northern hemisphere. Consistent water potential thresholds were found that resulted in mortality of our case study species, pinon pine and one-seed juniper. Extending these results with IPCC climate scenarios suggests that most existing trees in this region (SW USA) will be dead by 2050. Further, independent estimates of future mortality for the entire coniferous biome suggest widespread mortality by 2100. The validity and assumptions and implications of these results are discussed.

  14. Infection increases mortality in necrotizing pancreatitis

    DEFF Research Database (Denmark)

    Werge, Mikkel; Novovic, Srdan; Schmidt, Palle N

    2016-01-01

    OBJECTIVES: To assess the influence of infection on mortality in necrotizing pancreatitis. METHODS: Eligible prospective and retrospective studies were identified through manual and electronic searches (August 2015). The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Meta...... sterile necrosis and organ failure was associated with a mortality of 19.8%. If the patients had infected necrosis without organ failure the mortality was 1.4%. CONCLUSIONS: Patients with necrotizing pancreatitis are more than twice as likely to die if the necrosis becomes infected. Both organ failure...... and infected necrosis increase mortality in necrotizing pancreatitis....

  15. Treatment Factors That Influence Mortality in Acromegaly.

    Science.gov (United States)

    McCabe, John; Ayuk, John; Sherlock, Mark

    2016-01-01

    Acromegaly is a rare condition characterized by excessive secretion of growth hormone (GH), which is almost always due to a pituitary adenoma. Acromegaly is associated with significant morbidity such as hypertension, type 2 diabetes, cardiomyopathy, obstructive sleep apnoea, malignancy and musculoskeletal abnormalities. Acromegaly has also been associated with increased mortality in several retrospective studies. This review will focus on the epidemiological data relating to mortality rates in acromegaly, the relationship between acromegaly and malignancy, the role of GH and insulin-like growth factor-I in assessing the risk of future mortality, and the impact of radiotherapy and hypopituitarism on mortality.

  16. [Mortality as an index of social development].

    Science.gov (United States)

    Illanes, J P

    1984-01-01

    The author examines the use of measures of mortality as indicators of social development. Separate consideration is given to general mortality, infant mortality, and life expectancy. He concludes that the Chilean and Latin American mortality data cannot be analyzed separately from the available social data as a whole, and that the traditional health indicators for the measurement of social development continue to be valid. Comments by Ernesto Medina, Dagmar Raczynski, Juan P. Illanes, and Tarsicio Castaneda are included (pp. 107-14), as well as a reply to these comments by the author (pp. 114-6).

  17. RISK FACTORS OF MORTALITY IN NEONATAL ILLNESS

    Directory of Open Access Journals (Sweden)

    Jeyanthi

    2016-03-01

    Full Text Available BACKGROUND Infant Mortality Rate (IMR is high in India. Identification of risk factors of mortality in neonatal illness is essential to reduce Neonatal Mortality Rate (NMR and ultimately the IMR. AIM To identify the risk factors of mortality in neonatal illness. SETTING AND DESIGN It was a nested case control study done at the sick neonatal unit of urban tertiary referral centre. METHODS AND MATERIALS After obtaining ethical committee approval, retrospective analysis of 150 out born neonatal case records of babies admitted during the period from October 2015 to December 2015 was done. Data such as demographic features, maternal details, referral details, perinatal events, clinical features, laboratory reports and outcome were recorded. STATISTICAL ANALYSIS These risk factors were subjected to univariate and multivariate logistic regression analysis and P value calculated for the same to find out significant risk factors of mortality in neonatal illness. RESULTS Neonatal mortality rate was 22%. Male-to-female ratio was 2:1, death occurred more commonly in female neonates (23.1%. Home deliveries carried more risk of mortality. Birth order 4 and above had 25% mortality. Neonates of mother who had primary education and below had higher mortality. Perinatal asphyxia and sepsis were the most common causes of neonatal mortality. By univariate analysis, preterms had 4.9 times increased risk of mortality than term babies. Apnoeic spells, chest retractions and shock had 8 times, 3 times and 3.6 times increased risk of mortality respectively. By multivariate analysis, birth weight below 2 kilograms (kg carried 11.8 times more risk of mortality with a p value 0.00 (95% C.I 3.2, 30.4 and poor maternal intake of iron and folic acid tablets was 3.9 times more risk p value 0.003 (95% C.I 1.6, 9.6, apnoeic spells were 5.8 times more risk of mortality with p value 0.02 (95% C.I 1.3, 26.2. CONCLUSION Birth weight below 2 kg, poor maternal intake of iron and folic

  18. Mortality among Norwegian doctors 1960-2000

    Directory of Open Access Journals (Sweden)

    Hem Erlend

    2011-03-01

    Full Text Available Abstract Background To study the mortality pattern of Norwegian doctors, people in human service occupations, other graduates and the general population during the period 1960-2000 by decade, gender and age. The total number of deaths in the study population was 1 583 559. Methods Census data from 1960, 1970, 1980 and 1990 relating to education were linked to data on 14 main causes of death from Statistics Norway, followed up for two five-year periods after census, and analyzed as stratified incidence-rate data. Mortality rate ratios were computed as combined Mantel-Haenzel estimates for each sex, adjusting for both age and period when appropriate. Results The doctors had a lower mortality rate than the general population for all causes of death except suicide. The mortality rate ratios for other graduates and human service occupations were 0.7-0.8 compared with the general population. However, doctors have a higher mortality than other graduates. The lowest estimates of mortality for doctors were for endocrine, nutritional and metabolic diseases, diseases in the urogenital tract or genitalia, digestive diseases and sudden death, for which the numbers were nearly half of those for the general population. The differences in mortality between doctors and the general population increased during the periods. Conclusions Between 1960 and 2000 mortality for doctors converged towards the mortality for other university graduates and for people in human service occupations. However, there was a parallel increase in the gap between these groups and the rest of the population. The slightly higher mortality for doctors compared with mortality for other university graduates may be explained by the higher suicide rate for doctors.

  19. Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC) - Smoking Attributable Mortality (SAM)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2005-2009. SAMMEC - Smoking-Attributable Mortality, Morbidity, and Economic Costs. Smoking attributable mortality (SAM) is the number of deaths caused by cigarette...

  20. Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC) - Smoking-Attributable Mortality (SAM)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2005-2009. SAMMEC - Smoking-Attributable Mortality, Morbidity, and Economic Costs. Smoking-attributable mortality (SAM) is the number of deaths caused by cigarette...

  1. Trends in mortality decrease and economic growth

    NARCIS (Netherlands)

    Niu, G.; Melenberg, B.

    2014-01-01

    The vast literature on extrapolative stochastic mortality models focuses mainly on the extrapolation of past mortality trends and summarizes the trends by one or more latent factors. However, the interpretation of these trends is typically not very clear. On the other hand, explanation methods are t

  2. The Gestational Age Pattern of Human Mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas

    I present a lifetable by gestational age from week 23 until week 100 after the last menstrual period of the mother. The lifetable shows the pre-natal, peri-natal and post-natal mortality levels for US fetus/infants conceived in the year 2009. The observed age pattern of the force of mortality...

  3. Human mortality improvement in evolutionary context

    DEFF Research Database (Denmark)

    Burger, Oskar; Baudisch, Annette; Vaupel, James W

    2012-01-01

    about 4 of the roughly 8,000 human generations that have ever lived. Moreover, mortality improvement in humans is on par with or greater than the reductions in mortality in other species achieved by laboratory selection experiments and endocrine pathway mutations. This observed plasticity in age......-specific risk of death is at odds with conventional theories of aging....

  4. Computational Intelligence. Mortality Models for the Actuary

    NARCIS (Netherlands)

    Willemse, W.J.

    2001-01-01

    This thesis applies computational intelligence to the field of actuarial (insurance) science. In particular, this thesis deals with life insurance where mortality modelling is important. Actuaries use ancient models (mortality laws) from the nineteenth century, for example Gompertz' and Makeham's la

  5. 29 CFR 4044.53 - Mortality assumptions.

    Science.gov (United States)

    2010-07-01

    ... ASSETS IN SINGLE-EMPLOYER PLANS Valuation of Benefits and Assets Trusteed Plans 4044.53 Mortality... retirement benefit for any reason other than a change in the participant's health status. (2) Non-Social... the participant's health status. (g) Contingent annuitant mortality during deferral period. If...

  6. Mortality analysis in hip fracture patients

    DEFF Research Database (Denmark)

    Foss, N B; Kehlet, H

    2005-01-01

    Patients with hip fractures are usually frail and elderly with a 30-day mortality in excess of 10% in European series. Perioperative morbidity is often multifactorial in nature, and unimodal interventions will not necessarily decrease mortality. The purpose of this prospective study was to analys...

  7. Ventilator-associated pneumonia and mortality

    NARCIS (Netherlands)

    Melsen, W.G.

    2012-01-01

    Ventilator-associated Pneumonia (VAP) is one of the most common nosocomial infections among patients admitted to the intensive care unit. It is generally believed that VAP increases the mortality of patients, however exact determination of the attributable mortality of VAP is challenging. This thesi

  8. Predictive Factors of Mortality in Burn Patients

    OpenAIRE

    Fazeli; Karami-Matin; Kakaei; Pourghorban; Safari-Faramani

    2014-01-01

    Background: Burn injuries impose a considerable burden on healthcare systems in Iran. It is among the top ten causes of mortality and a main cause of disability. Objectives: This study aimed to examine factors influencing mortality in burn patients admitted to the main educational tertiary referral hospital in Kermanshah. Patients and Methods: All patients admitted to the Imam Khom...

  9. Rise in maternal mortality in the Netherlands

    NARCIS (Netherlands)

    J.M. Schutte; E.A.P. Steegers; N.W.E. Schuitemaker; J.G. Santema; K. de Boer; M. Pel; G. Vermeulen; W. Visser; J. van Roosmalen

    2010-01-01

    Objective To assess causes, trends and substandard care factors in maternal mortality in the Netherlands. Design Confidential enquiry into the causes of maternal mortality. Setting Nationwide in the Netherlands. Population 2,557,208 live births. Methods Data analysis of all maternal deaths in the pe

  10. Regional differences in Dutch maternal mortality.

    NARCIS (Netherlands)

    Graaf, J. de; Schutte, J.; Poeran, J.; Roosmalen, J. van; Bonsel, G.; Steegers, E.

    2012-01-01

    Please cite this paper as: de Graaf J, Schutte J, Poeran J, van Roosmalen J, Bonsel G, Steegers E. Regional differences in Dutch maternal mortality. BJOG 2012;119:582-588. Objective To study regional differences in maternal mortality in the Netherlands. Design Confidential inquiry into the causes of

  11. Maternal Mortality in the United States

    Science.gov (United States)

    Lee, Anne S.

    1977-01-01

    Figures from 1800 through 1973 are used to demonstrate that black women have had substantially higher rates of death in childbirth than white women. As mortality has declined, the relative difference between whites and blacks has actually increased. Factors affecting mortality and future prospects for reducing maternal deaths are discussed. (GC)

  12. Mortality in patients with Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, L; Stenager, E; Boldsen, J

    1995-01-01

    INTRODUCTION: After the introduction of L-dopa the mortality rate in Parkinson's disease (PD) patients has changed, but is still higher than in the background population. MATERIAL & METHODS: Mortality, age at death and cause of death in a group of PD patients compared with the background population...

  13. Modeling mortality : Empirical studies on the effect of mortality on annuity markets

    NARCIS (Netherlands)

    Hari, N.

    2007-01-01

    Chapter 3 of the dissertation models the macro-longevity risk and introduces a stochastic model for human mortality rates. Chapter 4 analyzes the importance of mortality improvement and mortality risk (macro- and micro-longevity risk and parameter uncertainty) on solvency positions of pension funds

  14. The Gestational Age Pattern of Human Mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas; Vaupel, James W.; Jacobsen, Rune;

    2016-01-01

    In order to check hypotheses about the cause for "ontogenescense" -- the phenomenon of a declining force of mortality prior to maturity -- I analyse data on human mortality by gestational age. Based on extensive microdata on births, fetal- and infant deaths in the US 2009 I calculate a joint fetal......-infant lifetable by gestational age spanning week 23 until week 100 after the last menstrual period of the mother. This joint lifetable shows a remarkable regularity in the gestational age profile of fetal- and infant mortality: Mortality rates are declining over the whole observed age range with the exception...... of a "birth hump" peaking week 38. The absolute rate of decline slows down over age. The observed gestational age pattern of the force of mortality is consistent with three hypotheses concerning the causes for ontogenescense: 1) Adaptation: as the organism growths it becomes more resilient towards death, 2...

  15. Percutaneous endoscopic gastrostomy and early mortality.

    Science.gov (United States)

    Clarkston, W K; Smith, O J; Walden, J M

    1990-12-01

    To assess morbidity, mortality, and benefit associated with percutaneous endoscopic gastronomy (PEG), we retrospectively studied 42 patients who had had PEG. Mortality was exceptionally high during the first 60 days after PEG (43%), and then stabilized. In nearly half of the cases (20/42) the PEG tube was removed during the first 60 days because of either death or improvement. Patients with malignancy had a significantly higher morbidity and 60-day mortality than the neurologically impaired. We concluded that patients should be carefully selected for PEG because early mortality is high; a 60-day trial of soft nasogastric feedings should be considered before PEG, and could reduce by nearly half the number of patients failing to receive long-term benefit; and patients with malignancy have significantly greater morbidity and mortality after PEG and may not receive the same advantage from the procedure.

  16. The healthy immigrant effect and mortality rates.

    Science.gov (United States)

    Ng, Edward

    2011-12-01

    According to the 2006 Census, almost the Canadian population were foreign-born, a percentage that is projected to reach at least 25% by 2031. Studies based on age-standardized mortality rates (ASMR) have found a healthy immigrant effect, with lower overall rates among immigrants. A duration effect has also been observed-immigrants' mortality advantage lessened as their time in Canada increased. ASMRs based on the 1991 to 2001 census mortality follow-up study indicate a healthy immigrant effect and a duration effect at the national level for all-cause mortality for both sexes. However, at the national level, the mortality rate among women from the United States and from Sub-Saharan Africa was similar to that of Canadian-born women. For the three largest Census Metropolitan Areas (Toronto, Montreal and Vancouver), a healthy immigrant effect was not observed among women or among most men from the United States or Sub-Saharan Africa.

  17. [Maternal mortality among black women in Brazil].

    Science.gov (United States)

    Martins, Alaerte Leandro

    2006-11-01

    Every minute a woman dies in the world due to labor or complications of pregnancy. Maternal mortality is a public health problem in Brazil and affects the country's various regions unequally. Researchers agree that maternal death occurs mainly in women with lower income and less schooling. The racial issue emerges in the midst of socioeconomic issues. The analysis is hampered by the difficulty in understanding Brazil's official classification of race/color, which often impedes recording this information. Various Maternal Mortality Committees are applying the color item and reviewing their data. The current article analyzes various Maternal Mortality Committee reports, showing that the risk of maternal mortality is greater among black women (which encompasses two census categories, negra, or black, and parda, or brown), thus representing a major expression of social inequality. The article concludes with a review of political and technical recommendations to decrease maternal mortality.

  18. Diagnostic interval and mortality in colorectal cancer

    DEFF Research Database (Denmark)

    Tørring, Marie Louise; Frydenberg, Morten; Hamilton, William;

    2012-01-01

    Objective To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). Study Design and Setting Three population-based studies in Denmark...... presentation, the association between the length of the diagnostic interval and 5-year mortality rate after the diagnosis of CRC was the same for all three types of data: displaying a U-shaped association with decreasing and subsequently increasing mortality with longer diagnostic intervals. Conclusion Unknown...... confounding and in particular confounding by indication is likely to explain the counterintuitive findings of higher mortality among patients with very short diagnostic intervals, but cannot explain the increasing mortality with longer diagnostic intervals. The results support the theory that longer...

  19. Vitamin D with calcium reduces mortality

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Avenell, Alison; Masud, Tahir

    2012-01-01

    Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either...... vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight......,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin...

  20. Antigua/Barbuda Cancer Mortality Study

    Directory of Open Access Journals (Sweden)

    GS Daniel

    2014-10-01

    Full Text Available Objective: To determine the cancer mortality rates in Antigua and Barbuda in an effort to enhance the profile of the country’s cancer burden. Method: Available data for 2001 to 2005 were analysed to obtain cancer mortality rates. Analysis was also made of the mortality/incidence ratios. Results: There were 354 cancer deaths – 208 males (age standardized rates (ASR 111.9 and 146 females (ASR 66.3. The main causes were prostate (ASR 53 and breast (ASR 22. The mortality rates for cancers of the lung (ASR 5.09 males, 2.49 females and brain/nervous system (ASR 0.45 males, 1.7 females were significantly lower than those in the Caribbean. Conclusion: Mortality rates were highest for sex-specific cancers, accounting for more than 50% of cancer deaths.

  1. 2001-2011年内蒙古炭疽流行病学特征分析%Epidemiological analysis of anthrax in Inner Mongolia from 2001 to 2011

    Institute of Scientific and Technical Information of China (English)

    李澄; 闫绍宏; 郭卫东; 王文瑞

    2012-01-01

    In this study, we analyzed the epidemiological features of anthrax in Inner Mongolia Autonomous Region (Inner Mongolia) from 2001 to 2011 with descriptive epidemiological methods and aimed to further strengthen the preventive control measures in this area. Results show that the cases of anthrax were repeatedly continuous in old epidemic areas, and the cases were mostly sporadic with occasional outbreaks. The incidences of anthrax in the eastern regions were higher than that in the western regions. The number of cases for male was higher than that for female. The farmer and herdsman were the majority of the incidence populations, and the largest infected age group was 30 to 59. Results of this research suggested that the livestock department and health department should lay stress on the establishment of cooperation mechanism, planning to carry out prevention measures of anthrax and minimize the hazards of that.%目的 分析2001-2011年内蒙古自治区炭疽流行病学特征.方法 应用描述流行病学方法对2001-2011年炭疽疫情资料进行分析.结果 炭疽发病呈现老疫区反复不断,散发为主,偶有暴发.东部地区发病高于西部地区.男性多于女性.农、牧民为主要发病群体.发病主要集中在30一59岁人群.结论 畜牧部门和卫生部门应建立协作机制,有计划的开展防治工作,使危害降到最低水平.

  2. Mortality in anesthesia: a systematic review

    Directory of Open Access Journals (Sweden)

    Leandro Gobbo Braz

    2009-01-01

    Full Text Available This systematic review of the Brazilian and worldwide literature aims to evaluate the incidence and causes of perioperative and anesthesia-related mortality. Studies were identified by searching the Medline and Scielo databases, followed by a manual search for relevant articles. Our review includes studies published between 1954 and 2007. Each publication was reviewed to identify author(s, study period, data source, perioperative mortality rates, and anesthesia-related mortality rates. Thirty-three trials were assessed. Brazilian and worldwide studies demonstrated a similar decline in anesthesia-related mortality rates, which amounted to fewer than 1 death per 10,000 anesthetics in the past two decades. Perioperative mortality rates also decreased during this period, with fewer than 20 deaths per 10,000 anesthetics in developed countries. Brazilian studies showed higher perioperative mortality rates, from 19 to 51 deaths per 10,000 anesthetics. The majority of perioperative deaths occurred in neonates, children under one year, elderly patients, males, patients of ASA III physical status or poorer, emergency surgeries, during general anesthesia, and cardiac surgery followed by thoracic, vascular, gastroenterologic, pediatric and orthopedic surgeries. The main causes of anesthesia-related mortality were problems with airway management and cardiocirculatory events related to anesthesia and drug administration. Our systematic review of the literature shows that perioperative mortality rates are higher in Brazil than in developed countries, while anesthesia-related mortality rates are similar in Brazil and in developed countries. Most cases of anesthesia-related mortality are associated with cardiocirculatory and airway events. These data may be useful in developing strategies to prevent anesthesia-related deaths.

  3. 炭疽恐怖事件人员危害定量评估研究状况和前瞻%Quantitative hazard assessment of persons against anthrax terrorism:research actualities and prospects

    Institute of Scientific and Technical Information of China (English)

    刘健; 祖正虎; 许晴; 张文斗; 黄培堂; 郑涛

    2011-01-01

    The assessment of bioterrorism, especially anthrax terrorism,has been developed a lot since 2001 anthrax attack in the United States. In this paper, by summarizing dispersion models calculating the concentration distribution of Bacillus anthracis spores and dose-response models determining the relationship between morbidity and spore dose, the research actualities and prospects in the current quantitative hazard assessment of persons against anthrax terrorism are reviewed.%2001年美国炭疽邮件恐怖事件发生后,相关学者对生物恐怖,特别是对炭痘恐怖事件的危害评估,展开了深入研究.本文从确定炭疽芽孢杆茵芽孢浓度分布的扩散模型和确定发病率同芽孢剂量关系的剂量响应模型两个方面,对目前炭疽恐怖事件的人员危害的定量评估研究状况和前瞻作一综述.

  4. 内蒙古兴安盟发生在2011年的一起炭疽爆发疫情分析%An epidemiological analysis of Anthrax outbreak in Hinggan League of Inner Mongolia in 2011

    Institute of Scientific and Technical Information of China (English)

    郭卫东; 海岩; 王文瑞; 金华瑞; 宋壮志; 跃华; 李忠延; 袁海涛

    2014-01-01

    Objective To analyze the epidemiological characteristics and the cause of infection of an Anthrax outbreak in 2011,in Hinggan League of Inner Mongolia,and in order to provide a scientific basis for prevention and control of Anthrax.Methods The epidemiological data was from investigation of an Anthrax outbreak and disease monitoring and reporting system of Hinggan League.Time,regional and population distribution of Anthrax cases were analyzed,and the pathogen of Anthrax cases in Hinggan League was detected in August to September 2011.Diagnosis of Anthrax was based on "Anthrax Diagnostic Criteria" (WS 283-2008).Results The Anthrax outbreak was occurred in 4 counties,11 townships (towns) and 20 villages of Hinggan League.A total of 55 Anthrax cases had been reported,of which 43 cases were suspected cutaneous Anthrax; 7 cases were clinically diagnosed; 7 cases were confirmed cases; 3 cases were died; 53 cases were cured.The cases of 72.73%(40/55) were reported in the period from 28~ August-8~ September; 47 cases were male patients,male to female ratio of 5.88:1.00; 70.91%(39/55) patients were aged 30-< 55 years and 85.45%(47/55) were farmers.All pateints had history of slaughtereing or contacing died animals and them products.Etiological examination results showed that no one Bacillus anthracis was isolated from all 55 blood samples,and there were 7 smear staining positive samples and 7 strains Bacillus anthracis were isolated from 55 skin exudate samples.Conclusions Young adults and farmers are at a high risk of Anthrax.The main cause of human Anthrax is slaughtering infected or died animals or meat contacting.Do not slaughtering,do not eat sick animals and do not sell dead livestock are the most effective measures for prevention and control of Anthracnose.%目的 分析内蒙古兴安盟2011年一起炭疽爆发案例流行病学特征及感染原因,为预防炭疽疫情的发生提出有效的防控措施.方法 疫情资料来源于兴安盟爆发疫情

  5. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

    Science.gov (United States)

    Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

    2010-01-01

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  6. Conifer Decline and Mortality in Siberia

    Science.gov (United States)

    Kharuk, V.; Im, S.; Ranson, K.

    2015-12-01

    "Dark needle conifer" (DNC: Abies sibirica, Pinus sibirica and Picea obovata) decline and mortality increase were documented in Russia during recent decades. Here we analyzed causes and scale of Siberian pine and fir mortality in Altai-Sayan and Baikal Lake Regions and West Siberian Plane based on in situdata and remote sensing (QuickBird, Landsat, GRACE). Geographically, mortality began on the margins of the DNC range (i.e., within the forest-steppe and conifer-broadleaf ecotones) and on terrain features with maximal water stress risk (narrow-shaped hilltops, convex steep south facing slopes, shallow well-drained soils). Within ridges, mortality occurred mainly along mountain passes, where stands faced drying winds. Regularly mortality was observed to decrease with elevation increase with the exception of Baikal Lake Mountains, where it was minimal near the lake shore and increased with elevation (up to about 1000 m a.s.l.). Siberian pine and fir mortality followed a drying trend with consecutive droughts since the 1980s. Dendrochronology analysis showed that mortality was correlated with vapor pressure deficit increase, drought index, soil moisture decrease and occurrence of late frosts. In Baikal region Siberian pine mortality correlated with Baikal watershed meteorological variables. An impact of previous year climate conditions on the current growth was found (r2 = 0.6). Thus, water-stressed trees became sensitive to bark beetles and fungi impact (including Polygraphus proximus and Heterobasidion annosum). At present, an increase in mortality is observed within the majority of DNC range. Results obtained also showed a primary role of water stress in that phenomenon with a secondary role of bark beetles and fungi attacks. In future climate with increased drought severity and frequency Siberian pine and fir will partly disappear from its current range, and will be substituted by drought-tolerant species (e.g., Pinus silvestris, Larix sibirica).

  7. Mortality Rates Among Arab Americans in Michigan

    OpenAIRE

    Dallo, Florence J.; Schwartz, Kendra; Ruterbusch, Julie J.; Booza, Jason; Williams, David R.

    2012-01-01

    The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, ...

  8. Association of Cardiometabolic Multimorbidity With Mortality

    DEFF Research Database (Denmark)

    Di Angelantonio, Emanuele; Kaptoge, Stephen; Wormser, David;

    2015-01-01

    IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using...... was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination...... of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity....

  9. Mortality associated with cervicofacial necrotizing fasciitis.

    Science.gov (United States)

    Roberson, J B; Harper, J L; Jauch, E C

    1996-09-01

    Cervicofacial necrotizing fasciitis is a rare infection but still occurs and carries a mortality rate up to 60%. It is a polymicrobial infection that is characterized by diffuse necrosis of fascial planes and subcutaneous tissues. Diagnosing early stages of cervicofacial necrotizing fasciitis in relationship to other soft tissue infections of odontogenic origin is difficult and leads to less aggressive treatment with resulting increased morbidity and mortality. To prevent this significant mortality and morbidity associated with cervicofacial necrotizing fasciitis early presentation, recognition and treatment by health care provider is essential.

  10. Mortality in mothers after perinatal loss

    DEFF Research Database (Denmark)

    Hvidtjørn, D; Wu, C; Schendel, D;

    2015-01-01

    OBJECTIVE: To assess whether mothers who lost a child from stillbirth or in the first week of life have an increased overall mortality and cause-specific mortality. DESIGN: A population based follow-up study. SETTING: Data from Danish national registers. POPULATION: All mothers in Denmark were...... included in the cohort at time of their first delivery from 1 January 1980 to 31 December 2008 and followed until 31 December 2009 or death, whichever came first. METHODS: The association between perinatal loss and total and cause-specific mortality in mothers was estimated with hazard ratios (HR) and 95...

  11. Social Welfare Expenditures and Infant Mortality.

    Science.gov (United States)

    Shim, Joyce

    2015-01-01

    This study examines the effects of social welfare expenditures on infant mortality (deaths younger than age 1 per 1,000 live births) across 19 Organisation for Economic Co-operation and Development (OECD) countries from 1980 to 2010. Data are obtained from various sources including the OECD, World Health Organization, and World Bank. The findings indicate that among three social welfare expenditure measures for families, the expenditures on family cash allowances are predicted to reduce infant mortality. However, the other two measures-the expenditures on parental and maternity leave and expenditures on family services-have no significant effects on infant mortality.

  12. Infant mortality: an insured population perspective.

    Science.gov (United States)

    Zimmerman, Daniel D; Roudebush, Brad

    2012-01-01

    Many insurers offer life coverage to individuals during the first year of life. The policies tend to have small face values, but frequently contain premium waiver or additional purchase options. General population mortality is significantly higher at this age relative to older children and even middle-aged adults. This article presents the mortality experience of an insured cohort in which death occurred under 1 year of age. In summary, the insured population's mortality rate was significantly lower and the leading causes of death were different than the general population.

  13. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses

    OpenAIRE

    Roberts, Nicholas J.; Zhang, Linping; Janku, Filip; Collins, Amanda; Bai, Ren-Yuan; Staedtke, Verena; Rusk, Anthony W.; Tung, David; Miller, Maria; Roix, Jeffrey; Khanna, Kristen V.; Murthy, Ravi; Benjamin, Robert S; Helgason, Thorunn; Szvalb, Ariel D.

    2014-01-01

    Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tum...

  14. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.

    Science.gov (United States)

    Roberts, Nicholas J; Zhang, Linping; Janku, Filip; Collins, Amanda; Bai, Ren-Yuan; Staedtke, Verena; Rusk, Anthony W; Tung, David; Miller, Maria; Roix, Jeffrey; Khanna, Kristen V; Murthy, Ravi; Benjamin, Robert S; Helgason, Thorunn; Szvalb, Ariel D; Bird, Justin E; Roy-Chowdhuri, Sinchita; Zhang, Halle H; Qiao, Yuan; Karim, Baktiar; McDaniel, Jennifer; Elpiner, Amanda; Sahora, Alexandra; Lachowicz, Joshua; Phillips, Brenda; Turner, Avenelle; Klein, Mary K; Post, Gerald; Diaz, Luis A; Riggins, Gregory J; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Bettegowda, Chetan; Huso, David L; Varterasian, Mary; Saha, Saurabh; Zhou, Shibin

    2014-08-13

    Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.

  15. Trends in mortality decrease and economic growth.

    Science.gov (United States)

    Niu, Geng; Melenberg, Bertrand

    2014-10-01

    The vast literature on extrapolative stochastic mortality models focuses mainly on the extrapolation of past mortality trends and summarizes the trends by one or more latent factors. However, the interpretation of these trends is typically not very clear. On the other hand, explanation methods are trying to link mortality dynamics with observable factors. This serves as an intermediate step between the two methods. We perform a comprehensive analysis on the relationship between the latent trend in mortality dynamics and the trend in economic growth represented by gross domestic product (GDP). Subsequently, the Lee-Carter framework is extended through the introduction of GDP as an additional factor next to the latent factor, which provides a better fit and better interpretable forecasts.

  16. Association between Integration Policies and Immigrants' Mortality

    DEFF Research Database (Denmark)

    Ikram, Umar Z; Malmusi, Davide; Juel, Knud;

    2015-01-01

    confounders and data comparability issues (e.g., French cross-sectional data) may affect the findings, this study suggests that different macro-level policy contexts may influence immigrants' mortality. Comparable mortality registration systems across Europe along with detailed socio-demographic information......BACKGROUND: To integrate immigrants into their societies, European countries have adopted different types of policies, which may influence health through both material and psychosocial determinants. Recent studies have suggested poorer health outcomes for immigrants living in countries with poorly...... rated integration policies. OBJECTIVE: To analyse mortality differences of immigrants from the same country of origin living in countries with distinct integration policy contexts. METHODS: From the mortality dataset collected in the Migrant Ethnic Health Observatory (MEHO) project, we chose...

  17. Increased mortality among people with anxiety disorders

    DEFF Research Database (Denmark)

    Meier, Sandra M; Mattheisen, Manuel; Mors, Ole;

    2016-01-01

    BACKGROUND: Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. AIMS......: To assess mortality risk in people with anxiety disorders. METHOD: We used nationwide Danish register data to conduct a prospective cohort study with over 30 million person-years of follow-up. RESULTS: In total, 1066 (2.1%) people with anxiety disorders died during an average follow-up of 9.7 years....... The risk of death by natural and unnatural causes was significantly higher among individuals with anxiety disorders (natural mortality rate ratio (MRR) = 1.39, 95% CI 1.28-1.51; unnatural MRR = 2.46, 95% CI 2.20-2.73) compared with the general population. Of those who died from unnatural causes, 16.5% had...

  18. Polysomnographic indicators of mortality in stroke patients

    DEFF Research Database (Denmark)

    Ponsaing, Laura B; Iversen, Helle K; Jennum, Poul

    2017-01-01

    PURPOSE: The purpose of the study was to assess polysomnographic indicators of increased mortality risk in patients with stroke or a transient ischemic attack (TIA). METHODS: We performed polysomnographies in 63 acute stroke/TIA patients. Mortality data were collected from a national database after...... a 19-37-month follow-up period. RESULTS: Of the 57 stroke and 6 TIA patients, 9 stroke patients died during follow-up. All nine had moderate or severe sleep-related breathing disorders (SRBDs). Binarily divided, the group with the highest apnea hypopnea index (AHI) had an almost 10-fold higher.......92; 95 % CI 2.00-49.23; p = 0.005), and there was a trend toward a higher mortality risk with atrial fibrillation/flutter (HR 3.63; 95 % CI 0.97-13.51; p = 0.055). CONCLUSIONS: In stroke patients, the AHI and nocturnal wake time are indicators of increased mortality risk. SRBDs in stroke patients should...

  19. Infant mortality and crisis in Mexico.

    Science.gov (United States)

    Bronfman, M

    1992-01-01

    Data derived from the Encuesta Nacional de Fecundidad y Salud (ENFES) confirm that overall levels of infant mortality in Mexico have been steadily declining. However, a more specific analysis furnishes evidence that this decline has occurred at varying rates within different social groups, reflecting an increase in social inequalities. The analytical strategy used in this article leads to three basic conclusions: (1) the impact of the economic crisis on infant mortality is reflected not in a reversal of the declining trend but an increase in social inequalities; (2) certain variables universally accepted as determinants of infant mortality, such as mother's education, seem nonsignificant for some social sectors; and (3) certain biodemographic characteristics assumed to have a uniform mortality-related behavior vary among sectors, suggesting that even these constants are determined by social factors.

  20. MATERNAL MORTALITY IN A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Harpreet

    2013-06-01

    Full Text Available ABSTRACT: Maternal Mortality in A Tertiary Care Centre. OBJECTIVE: To study maternal mortality and the complications leading to maternal death. METHODS: A retrospective study of hospital record to study maternal mortality and its causes over 3 years from January 2010 to December 2012. RESULTS: There were a total of 58 maternal deaths out of 2823 live births giving a maternal mortality ratio of 2054.55 per one lakh live births. Unbooked and late referrals account for 77.58% of maternal deaths. The majority of deaths around 75.86% were in 20-30 years age group. Haemorrhage was the commonest causes of death (24.12% followed by sepsis (18.96% and pregnancy induced hypertension 15.51% Anemia contributed to the most common indirect cause of maternal morality. CONCLUSION: Haemorrhage, sepsis and pregnancy induced hypertension including eclampsia were the direct major causes of death. Anaemia and cardiac diseases were other indirect causes of death.

  1. Excess mortality in patients diagnosed with hypothyroidism

    DEFF Research Database (Denmark)

    Thvilum, Marianne; Brandt, Frans; Pedersen, Dorthe Almind

    2013-01-01

    Background: Although hypothyroidism is associated with increased morbidity, an association with increased mortality is still debated. Our objective was to investigate, at a nationwide level, whether a diagnosis of hypothyroidism influences mortality. Methods: In an observational cohort study from...... January 1, 1978 until December 31, 2008 using record-linkage data from nationwide Danish health registers, 3587 singletons and 682 twins diagnosed with hypothyroidism were identified. Hypothyroid individuals were matched 1:4 with nonhypothyroid controls with respect to age and gender and followed over...... a mean period of 5.6 years (range 0-30 years). The hazard ratio (HR) for mortality was calculated using Cox regression analyses. Comorbidity was evaluated using the Charlson score (CS). Results: In singletons with hypothyroidism, the mortality risk was increased (HR 1.52; 95% confidence interval [CI]: 1...

  2. Excess mortality in giant cell arteritis

    DEFF Research Database (Denmark)

    Bisgård, C; Sloth, H; Keiding, Niels

    1991-01-01

    A 13-year departmental sample of 34 patients with definite (biopsy-verified) giant cell arteritis (GCA) was reviewed. The mortality of this material was compared to sex-, age- and time-specific death rates in the Danish population. The standardized mortality ratio (SMR) was 1.8 (95% confidence...... with respect to SMR, sex distribution or age. In the group of patients with department-diagnosed GCA (definite + probable = 180 patients), the 95% confidence interval for the SMR of the women included 1.0. In all other subgroups there was a significant excess mortality. Excess mortality has been found in two...... of seven previous studies on survival in GCA. The prevailing opinion that steroid-treated GCA does not affect the life expectancy of patients is probably not correct....

  3. Illness Human - MDC_InfantMortality2006

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — Polygon feature class based on Zip Code boundaries showing the rate of infant mortality per 1000 births in Miami-Dade County, 2006. Rate does not include out of...

  4. Association of Cardiometabolic Multimorbidity With Mortality

    NARCIS (Netherlands)

    Di Angelantonio, Emanuele; Kaptoge, Stephen; Wormser, David; Willeit, Peter; Butterworth, Adam S; Bansal, Narinder; O'Keeffe, Linda M; Gao, Pei; Wood, Angela M; Burgess, Stephen; Freitag, Daniel F; Pennells, Lisa; Peters, Sanne A; Hart, Carole L; Håheim, Lise Lund; Gillum, Richard F; Nordestgaard, Børge G; Psaty, Bruce M; Yeap, Bu B; Knuiman, Matthew W; Nietert, Paul J; Kauhanen, Jussi; Salonen, Jukka T; Kuller, Lewis H; Simons, Leon A; van der Schouw, Yvonne T; Barrett-Connor, Elizabeth; Selmer, Randi; Crespo, Carlos J; Rodriguez, Beatriz; Verschuren, W M Monique; Salomaa, Veikko; Svärdsudd, Kurt; van der Harst, Pim; Björkelund, Cecilia; Wilhelmsen, Lars; Wallace, Robert B; Brenner, Hermann; Amouyel, Philippe; Barr, Elizabeth L M; Iso, Hiroyasu; Onat, Altan; Trevisan, Maurizio; D'Agostino, Ralph B; Cooper, Cyrus; Kavousi, Maryam; Welin, Lennart; Roussel, Ronan; Hu, Frank B; Sato, Shinichi; Davidson, Karina W; Howard, Barbara V; Leening, Maarten J G; Leening, Maarten; Rosengren, Annika; Dörr, Marcus; Deeg, Dorly J H; Kiechl, Stefan; Stehouwer, Coen D A; Nissinen, Aulikki; Giampaoli, Simona; Donfrancesco, Chiara; Kromhout, Daan; Price, Jackie F; Peters, Annette; Meade, Tom W; Casiglia, Edoardo; Lawlor, Debbie A; Gallacher, John; Nagel, Dorothea; Franco, Oscar H; Assmann, Gerd; Dagenais, Gilles R; Jukema, J Wouter; Sundström, Johan; Woodward, Mark; Brunner, Eric J; Khaw, Kay-Tee; Wareham, Nicholas J; Whitsel, Eric A; Njølstad, Inger; Hedblad, Bo; Wassertheil-Smoller, Sylvia; Engström, Gunnar; Rosamond, Wayne D; Selvin, Elizabeth; Sattar, Naveed; Thompson, Simon G; Danesh, John

    2015-01-01

    IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using indi

  5. [Maternal mortality: levels, trends, and differentials].

    Science.gov (United States)

    Langer, A; Lozano, R; Hernandez, B

    1993-01-01

    Maternal mortality in Mexico has declined significantly over the past half century. The maternal mortality rate was 53/10,000 live births in 1940 and 5.1 in 1990. The greatest and most rapid decline occurred in the 1940s. The maternal mortality rate is still too high, and in addition the differential between Mexican rates and those of the developed countries has increased. The average age at maternal death is 29 years, a full 40 years less than potential life expectancy. The risk of death from causes related to reproduction varies substantially by educational level. Of all maternal deaths between 1986 and 1991, 26% were in illiterate women, 33% in women with incomplete primary, and 24% in those with complete primary. In 1990, the average female school attainment was complete primary. The maternal mortality rate was eight times higher among illiterate women and five times higher in those not completing primary than in those finishing preparatory. Geographically, states with low maternal mortality rates of under 3.1 are mainly located in the north and those with high maternal mortality of over 6.0 are in the south. The central zone is an intermediate area. The 1991 maternal mortality rates of Oaxaca, Puebla, Tlaxcala, Veracruz, and the state of Mexico are similar to those of Nuevo Leon 30 years ago or Aguascalientes, Sonora, and Baja California 20 years ago. 72% of maternal deaths in the 1980s occurred in rural areas. The rates were 6.5/10,000 in rural areas and 4.1/10,000 in urban areas. The maternal mortality rate also increases with marginalization. An index of marginalization constructed with census data using multivariate techniques showed that fertile aged women in very marginalized municipios had maternal mortality rates of 11.5/10,000, or a risk of death three times greater than women in municipios scoring low for marginalization. Maternal mortality continues to be a priority public health problem in Mexico. Because so many maternal deaths are preventable

  6. 应用噬菌体进行炭疽疫苗纯菌检查方法的建立%Application of phage for the detection of purity of anthrax vaccine

    Institute of Scientific and Technical Information of China (English)

    魏东; 李恪梅; 王国治

    2012-01-01

    目的 建立应用噬菌体进行炭疽活疫苗纯菌检查的方法,并与现用纯菌检查方法进行比较.方法 使用噬菌体对与炭疽芽孢杆菌分类学上接近以及常见污染细菌进行裂解观察,确定噬菌体特异性.选取具有代表性的可能污染菌定量掺入炭疽疫苗中,制备模拟污染疫苗,进行噬菌体裂解纯菌检查方法的灵敏度研究,同时与现用的直接接种纯菌检查方法进行比较.结果 炭疽噬菌体能特异地裂解炭疽芽孢杆菌,对与炭疽芽孢杆菌分类学上接近以及常见污染细菌无裂解作用.噬菌体裂解法对掺入炭疽疫苗中蜡样芽孢杆菌、枯草芽孢杆菌及大肠埃希菌的检出限均为1 CFU/人份,而现用纯菌检查方法的检出限分别为5、5及50 CFU/人份.结论 噬菌体裂解法检测炭疽活疫苗中污染菌有较好的特异性和灵敏度,该方法的应用对疫苗质量控制具有重要意义.%Objective To develop phage lysis method for the detection of purity of anthrax vaccine and to compare phage lysis method with the routine method .Methods Nine strains of non-Bacillus anthracis were lysed with anthrax phage to evaluate the specificity of phage .The quantified three strains of non-Bacillus anthracis were respectively added into anthrax vaccine to evaluate the sensitivity of phage ,which was compared with the routine method .Results The anthrax phage could lyse Bacillus anthracis and without cross-reaction with other strains of non-Bacillus anthracis .The detection limit of phage lysis method for detection of Bacillus cereus ,Bacillus subtilis and Escherichia coli ,which were added into anthrax vaccine ,were all 1 CFU /dose .The detection limit of routine method for Bacillus cereus ,Bacillus subtilis and Escherichia coli were 5 ,5 and 50 CFU /dose .Conclusion Phage lysis method might be sensitive and specific for detection of purity of anthrax vaccine . This method could be with the potential to be used as a

  7. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers.

    Science.gov (United States)

    Hopkins, Robert J; Daczkowski, Nancy F; Kaptur, Paulina E; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L; Bernton, Edward

    2013-06-26

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax(®) (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18-50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA+0.5mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA+0.25mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA+0.5mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA+0.25mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909.

  8. Socioeconomic trajectories affect mortality in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Bojesen, Anders; Krag, Kirstine Stochholm; Juul, Svend

    2011-01-01

    Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status?......Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status?...

  9. Mortality in patients with pituitary disease.

    LENUS (Irish Health Repository)

    Sherlock, Mark

    2010-06-01

    Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing\\'s disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

  10. Mortality by sickle cell disease in Brazil.

    Science.gov (United States)

    Arduini, Giovanna Abadia Oliveira; Rodrigues, Letícia Pinto; Trovó de Marqui, Alessandra Bernadete

    This work aimed to characterize mortality by sickle cell disease in Brazil. The MEDLINE electronic database was searched using the terms 'mortality' and 'sickle cell disease' and 'Brazil' for articles published in the last five years aiming to provide a current analysis of the subject in question. Eight studies on mortality by sickle cell disease were carried out in the Brazilian states of Maranhão, Bahia, Minas Gerais, Rio de Janeiro and Mato Grosso do Sul. The majority of the deaths occurred in patients with sickle cell anemia, which is the most common genotype and causes the most severe clinical manifestation of the disease. In summary, there are few published studies on mortality related to sickle cell disease in Brazil, and most are from the state of Minas Gerais. This study emphasizes the importance of developing more studies on sickle cell disease mortality, so that it may be possible to profile gene carriers and give health professionals more data to strategize the delivery of more effective assistance to these individuals. Despite the early diagnosis of sickle cell disease by the Neonatal Screening Program and the use of preventive and therapeutic measures (penicillin, immunization and hydroxyurea), mortality by sickle cell disease on the world stage is still significant.

  11. Alcohol Consumption and Pancreatitis Mortality in Russia

    Directory of Open Access Journals (Sweden)

    Yury E Razvodovsky

    2014-07-01

    Full Text Available Context Pancreatitis is a major public health problem with high associated economic costs. The incidence of pancreatitis has increased in many European countries in recent decade. Accumulated research and empirical evidence suggests that excessive alcohol consumption is a major risk factor for both acute and chronic pancreatitis. Objective The aim of this study was to examine the aggregate-level relation between the alcohol consumption and pancreatitis mortality rates in Russia. Method Age-standardized sex-specific male and female pancreatitis mortality data for the period 1970-2005 and data on overall alcohol consumption were analyzed by means ARIMA (autoregressive integrated moving average time series analysis. Alcohol consumption was significantly associated with both male and female pancreatitis mortality rates: a 1 liter increase in overall alcohol consumption would result in a 7.0% increase in the male pancreatitis mortality rate and in 2.3% increase in the female mortality rate. The results of the analysis suggest that 63.1% of all male pancreatitis deaths and 26.8% female deaths in Russia could be attributed to alcohol. Conclusions The outcomes of this study provide indirect support for the hypothesisthat unfavorable mixture of higher overall level of alcohol consumption and binge drinking pattern is an important contributor to the pancreatitis mortality rate in Russian Federation.

  12. Doctors' strikes and mortality: a review.

    Science.gov (United States)

    Cunningham, Solveig Argeseanu; Mitchell, Kristina; Narayan, K M; Yusuf, Salim

    2008-12-01

    A paradoxical pattern has been suggested in the literature on doctors' strikes: when health workers go on strike, mortality stays level or decreases. We performed a review of the literature during the past forty years to assess this paradox. We used PubMed, EconLit and Jstor to locate all peer-reviewed English-language articles presenting data analysis on mortality associated with doctors' strikes. We identified 156 articles, seven of which met our search criteria. The articles analyzed five strikes around the world, all between 1976 and 2003. The strikes lasted between nine days and seventeen weeks. All reported that mortality either stayed the same or decreased during, and in some cases, after the strike. None found that mortality increased during the weeks of the strikes compared to other time periods. The paradoxical finding that physician strikes are associated with reduced mortality may be explained by several factors. Most importantly, elective surgeries are curtailed during strikes. Further, hospitals often re-assign scarce staff and emergency care was available during all of the strikes. Finally, none of the strikes may have lasted long enough to assess the effects of long-term reduced access to a physician. Nonetheless, the literature suggests that reductions in mortality may result from these strikes.

  13. Mortality rates among Arab Americans in Michigan.

    Science.gov (United States)

    Dallo, Florence J; Schwartz, Kendra; Ruterbusch, Julie J; Booza, Jason; Williams, David R

    2012-04-01

    The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, all-cause and cause-specific mortality rates for Arab Americans were in the range of whites and blacks. However, Arab American men had lower mortality rates from cancer and chronic lower respiratory disease compared to both whites and blacks. Among women, Arab Americans had lower mortality rates from heart disease, cancer, stroke, and diabetes than whites and blacks. Arab Americans are growing in number. Future study should focus on designing rigorous separate analyses for this population.

  14. A biologically motivated partitioning of mortality.

    Energy Technology Data Exchange (ETDEWEB)

    Carnes, B. A.; Olshansky, S. J.; Center for Mechanistic Biology and Biotechnology; Univ. of Chicago

    1997-01-01

    For over a century, actuaries and biologists working independently of each other have presented arguments for why total mortality needs to be partitioned into biologically meaningful subcomponents. These mortality partitions tended to overlook genetic diseases that are inherited because the partitions were motivated by a paradigm focused on aging. In this article, we combine and extend the concepts from these disciplines to develop a conceptual partitioning of total mortality into extrinsic and intrinsic causes of death. An extrinsic death is either caused or initiated by something that originates outside the body of an individual, while an intrinsic death is either caused or initiated by processes that originate within the body. It is argued that extrinsic mortality has been a driving force in determining why we die when we do from intrinsic causes of death. This biologically motivated partitioning of mortality provides a useful perspective for researchers interested in comparative mortality analyses, the consequences of population aging, limits to human life expectancy, the progress made by the biomedical sciences against lethal diseases, and demographic models that predict the life expectancy of future populations.

  15. Religious Affiliation, Religious Service Attendance, and Mortality.

    Science.gov (United States)

    Kim, Jibum; Smith, Tom W; Kang, Jeong-han

    2015-12-01

    Very few studies have examined the effects of both religious affiliation and religiosity on mortality at the same time, and studies employing multiple dimensions of religiosity other than religious attendance are rare. Using the newly created General Social Survey-National Death Index data, our report contributes to the religion and mortality literature by examining religious affiliation and religiosity at the same time. Compared to Mainline Protestants, Catholics, Jews, and other religious groups have lower risk of death, but Black Protestants, Evangelical Protestants, and even those with no religious affiliation are not different from Mainline Protestants. While our study is consistent with previous findings that religious attendance leads to a reduction in mortality, we did not find other religious measures, such as strength of religious affiliation, frequency of praying, belief in an afterlife, and belief in God to be associated with mortality. We also find interaction effects between religious affiliation and attendance. The lowest mortality of Jews and other religious groups is more apparent for those with lower religious attendance. Thus, our result may emphasize the need for other research to focus on the effects of religious group and religious attendance on mortality at the same time.

  16. PREVALENT DISEASES AND OVERALL MORTALITY IN BROILERS

    Directory of Open Access Journals (Sweden)

    M. Farooq, Zahir-ud-Din, F .R. Durrani, M.A. Mian, N. Chand and J. Ahmed1

    2002-03-01

    Full Text Available Records from 62-broiler farms located in Swat, North West Frontier Province (NWFP, Pakistan were, collected during the year 1998 to investigate prevalent diseases and overall mortality in broilers. Losses due Hydro-pericardium syndrome (HPS were the highest (17.05 ± 2.08% and the lowest due to coccidiosis 9.39 ± 3.82%. Non-significant differences existed in mortality caused by Newcastle, IBD and yolk sac infection. Differences in losses caused by infectious coryza, enteritis and coccidiosis were also non- significant. Average overall mortality was 13.05 ± 1.16%, representing 7.59 ± 0.46% losses from day-1 to day 14 and 18.52 ± 0.95% from day-15 till marketing of broilers (42-50 days. Lower (p<0.05 overall mortality was observed in broilers reared on well-finished concrete floors (12.43 ± 1.45 % than in those on brick+mud made floors (14.36 ± 1.55. Higher (p<0.05 overall mortality was found in overcrowded houses 5.60 ± 5.62% than in optimally utilized houses (10.69 ± 1.51%. Overall mortality was higher (p<0.05 in flocks under substandard vaccination schedule (15.92 ± 1.55% than in those maintained under standard lancination schedule (10.20 ± 1.21%. Overall mortality was higher (21.11 ± 3.39% when the interval between two batches was ≤ 7 days than 16-20 days (5.72 ± 3.01%. Lower (p<0.05 overall mortality was und in broilers maintained under good hygienic ( 11.59 ±1.93% and sanitary conditions ( 10.82 ± 1.16% compared to those under poor hygienic and sanitary conditions (14.12 ± 2.81% and 15.15 ± 1.68 %respectively. Maintenance of broilers under good hygienic conditions on well finished concrete floor, providing the required space/broiler, following recommended vaccination schedule without HPS vaccine and keeping 8.20 days interval between two batches were suggested as key factors in reducing mortality among broilers in Swat

  17. Labor migration and child mortality in Mozambique

    Science.gov (United States)

    Yabiku, Scott T.; Agadjanian, Victor; Cau, Boaventura

    2013-01-01

    Male labor migration is widespread in many parts of the world, yet its consequences for child outcomes and especially childhood mortality remain unclear. Male labor migration could bring benefits, in the form of remittances, to the families that remain behind and thus help child survival. Alternatively, the absence of a male adult could imperil the household's well-being and its ability to care for its members, increasing child mortality risks. In this analysis, we use longitudinal survey data from Mozambique collected in 2006 and 2009 to examine the association between male labor migration and under-five mortality in families that remain behind. Using a simple migrant/non-migrant dichotomy, we find no difference in mortality rates across migrant and non-migrant men's children. When we separated successful from unsuccessful migration based on the wife's perception, however, stark contrasts emerge: children of successful migrants have the lowest mortality, followed by children of non-migrant men, followed by the children of unsuccessful migrants. Our results illustrate the need to account for the diversity of men's labor migration experience in examining the effects of migration on left-behind households. PMID:23121856

  18. Early retirement and mortality in Germany.

    Science.gov (United States)

    Kühntopf, Stephan; Tivig, Thusnelda

    2012-02-01

    Differences in mortality by retirement age have an important impact on the financing of pension insurance, yet no clear-cut results for Germany exist so far. We calculate mortality rates by retirement age from microdata on all German old-age pensioners and 1.84 million deceases. The life expectancies and survival probabilities at age 65 are estimated for population subgroups according to creditable periods because of disease and pension income. Early-retired men who reach the age of 65 years live significantly longer the later early retirement occurs; the life expectancy at age 65 ranges from 13 to 17.8 years. For each retirement age, mortality of men is higher the more periods of disease are credited in the pension insurance system. For a given length of credited periods of disease, mortality of early retirees decreases with the retirement age. 'Healthy worker selection effects' operating in the labour market may contribute to these results. The 'work longer, live longer'-result is found for each pension income quintile, which resolves the J-curve pattern found in the literature. The mortality of female old-age pensioners varies little with retirement age.

  19. Drought-mortality relationships for tropical forests.

    Science.gov (United States)

    Phillips, Oliver L; van der Heijden, Geertje; Lewis, Simon L; López-González, Gabriela; Aragão, Luiz E O C; Lloyd, Jon; Malhi, Yadvinder; Monteagudo, Abel; Almeida, Samuel; Dávila, Esteban Alvarez; Amaral, Iêda; Andelman, Sandy; Andrade, Ana; Arroyo, Luzmila; Aymard, Gerardo; Baker, Tim R; Blanc, Lilian; Bonal, Damien; de Oliveira, Atila Cristina Alves; Chao, Kuo-Jung; Cardozo, Nallaret Dávila; da Costa, Lola; Feldpausch, Ted R; Fisher, Joshua B; Fyllas, Nikolaos M; Freitas, Maria Aparecida; Galbraith, David; Gloor, Emanuel; Higuchi, Niro; Honorio, Eurídice; Jiménez, Eliana; Keeling, Helen; Killeen, Tim J; Lovett, Jon C; Meir, Patrick; Mendoza, Casimiro; Morel, Alexandra; Vargas, Percy Núñez; Patiño, Sandra; Peh, Kelvin S-H; Cruz, Antonio Peña; Prieto, Adriana; Quesada, Carlos A; Ramírez, Fredy; Ramírez, Hirma; Rudas, Agustín; Salamão, Rafael; Schwarz, Michael; Silva, Javier; Silveira, Marcos; Slik, J W Ferry; Sonké, Bonaventure; Thomas, Anne Sota; Stropp, Juliana; Taplin, James R D; Vásquez, Rodolfo; Vilanova, Emilio

    2010-08-01

    *The rich ecology of tropical forests is intimately tied to their moisture status. Multi-site syntheses can provide a macro-scale view of these linkages and their susceptibility to changing climates. Here, we report pan-tropical and regional-scale analyses of tree vulnerability to drought. *We assembled available data on tropical forest tree stem mortality before, during, and after recent drought events, from 119 monitoring plots in 10 countries concentrated in Amazonia and Borneo. *In most sites, larger trees are disproportionately at risk. At least within Amazonia, low wood density trees are also at greater risk of drought-associated mortality, independent of size. For comparable drought intensities, trees in Borneo are more vulnerable than trees in the Amazon. There is some evidence for lagged impacts of drought, with mortality rates remaining elevated 2 yr after the meteorological event is over. *These findings indicate that repeated droughts would shift the functional composition of tropical forests toward smaller, denser-wooded trees. At very high drought intensities, the linear relationship between tree mortality and moisture stress apparently breaks down, suggesting the existence of moisture stress thresholds beyond which some tropical forests would suffer catastrophic tree mortality.

  20. [Methods for diminishing mortality from infectious diseases].

    Science.gov (United States)

    Boev, B V; Ershov, F I

    2009-01-01

    The paper reports analysis of the "Russian Cross" demographic phenomenon characteristic of the present-day Russia, that is a marked excess of mortality over the birth rate leading to the reduction of the country's population at a rate of 750-800 thou people per year. The main causes and factors of excess mortality are considered with reference to deaths from infectious (viral and microbial) diseases. Experts of the Russian Academy of Medical Sciences proposed the working concept of the research program "Avoidable population mortality from infectious diseases in 2010-2020". Its implementation envisages the use of up-to-date information and computer technologies including mathematical and computer simulation of morbidity and mortality processes in outbreaks and epidemics of infectious diseases. The use of computer-assisted technologies is illustrated by the example of smallpox epidemics. They permit to promptly analyse and prognosticate excess mortality from infectious diseases by applying new diagnostic tools and medicinal products. This approach is proposed for the evaluation of the effectiveness of different projects in the framework of the above program. Its realization requires the development of three special information (computer-aided) systems designated Projects, Infections, and Prognoses.

  1. Electrohydrodynamic mortality of insects: a plausible mechanism

    Science.gov (United States)

    Shayesteh, N.; Barthakur, N. N.

    An electrohydrodynamic (EHD) system with a point-to-plane electrode, which produced air ions within a strong electric field, was used to study mortalities of pupae, larvae, and adults of Tribolium confusum (TC) and larvae of Plodia interpunctella (PI). The treatments included a neutral air stream, negative ions, positive ions, and the air stream superimposed with ions of either polarity. The negative ions caused the maximum mortality in TC pupae and PI larvae whereas the TC adults were least affected, but the negative ion flux was higher than the positive one at the constant high voltage of the power supply used in the present experiments. The differences in the mean mortalities of the treatment groups were highly significant (P<0.0001). Mortality was primarily attributed to the body fluid losses caused by the electric wind of the EHD system. Mortality and weight loss relationships were linear with negative slopes (r2=0.52, and r2=0.98 for TC and PI, respectively). The superimposition of the air stream with either positive or negative ion fluxes increased the survival fractions compared with those of the ion fluxes alone.

  2. Perinatal mortality and socio-spatial inequalities

    Directory of Open Access Journals (Sweden)

    Eunice Francisca Martins

    2013-09-01

    Full Text Available OBJECTIVE: to analyze the social inequalities in the distribution of perinatal mortality in Belo Horizonte. MATERIAL AND METHODS: the perinatal deaths of residents in Belo Horizonte in the period 2003 to 2007 were studied on the basis of the Information Systems on Mortality and Newborns. The space analysis and the Health Vulnerability Index were used to identify existing inequalities in the sanitary districts regarding coverage and risk, determined by the Odds Ratio and a value p<0.05. The multivariate analysis was used to describe a model for perinatal mortality. RESULTS: there was a proved variation in the numbers of perinatal mortality per one thousand total births in the sanitary districts (12.5 to 19.4, coverage areas (5.3 to 49.4 and areas of risk (13.2 to 20.7. The mortality rate diminished as the maternal schooling increased. The death rates deriving from asphyxia/hypoxia and non-specified fetal death grew with the increase of risk in the area. CONCLUSION: it was verified that the perinatal deaths are distributed in a differentiated form in relation to the space and the social vulnerabilities. The confrontation of this complex problem requires the establishment of intersecting partnerships.

  3. Enhanced surveillance of maternal mortality in Texas.

    Science.gov (United States)

    Estes, Larissa J; Lloyd, Linda E; Selwyn, Beatrice J

    2012-12-01

    Maternal mortality is often used to measure health and well-being for women. Improved surveillance efforts can improve maternal mortality estimates and inform the development of strategies to address the needs of maternal and child health populations. The purpose of this study was to provide better estimates of maternal mortality in Texas by using enhanced surveillance methods. Results from our analyses of fetal death and live birth records in Texas from 2000 through 2006 were then linked to pregnancy-related death records and death records of women of childbearing age (15-44 years) in Texas from 2001 through 2006. Enhanced surveillance identified almost 3.5 times as many deaths that might be associated with pregnancy than do current methods and confirmed a persistent race/ethnicity trend in maternal mortality. The leading cause of these 2001-2006 pregnancy-associated deaths was accidents. Enhanced surveillance allows the identification of additional deaths possibly associated with pregnancy and provides a stable foundation to investigate trends further and to review maternal mortality cases systematically.

  4. Trends of lung cancer mortality in Mexico.

    Science.gov (United States)

    Lazcano Ponce, E C; Tovar Guzman, V; Meneses Gonzalez, F; Rascon Pacheco, R A; Hernandez Avila, M

    1997-01-01

    Lung cancer (LC) is one of the most important public health problems in the world; 1,035,000 annual deaths are estimated each year and more than 80% of these are attributed to tobacco. The trend of lung cancer mortality in Mexico City from 1979 - 1993 was determined, as was the rate ratio of lung cancer mortality in 31 states in Mexico, taking Mexico City as a reference by means of a Poisson model. A strong linear regression model was used to evaluate the rate, where the dependent variable was LC mortality rate and the independent variable the year observed. In 15 years, 73,807 deaths from LC were reported, with an increase in mortality from 5.01 - 7.25 per 100,000 inhabitants. Mortality increases significantly after 60 years of age (B not equal to 0), ptax on cigarettes should be increased, smoking restricted in squares and public spaces, and the risks should be announced on cigarette packages, among other measures. With respect to other emergent risk factors, the sources of industrial pollution and toxic emissions should be regulated.

  5. Mortality in Levodopa-Treated Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    John C. Morgan

    2014-01-01

    Full Text Available Parkinson’s disease (PD is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960’s, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers. We undertook this retrospective study of 211 deceased PD patients to determine the factors associated with mortality in levodopa-treated PD. Our findings confirm that PD is associated with increased mortality in both men and women. Unlike the majority of other mortality studies, we found that women have a greater reduction in lifespan compared to men. We also found that patients with early onset PD (onset at the age of 50 or before have reduced survival relative to PD patients with later ages of onset. A final important finding is that survival is equal in PD patients treated with levodopa early (within 2 years or less of PD onset versus later.

  6. Mortality among rubber workers: V. processing workers.

    Science.gov (United States)

    Delzell, E; Monson, R R

    1982-07-01

    Cause-specific mortality was evaluated among 2,666 men employed in the processing division of a rubber manufacturing plant. The division was divided into two sections: front processing (compounding, mixing and milling operations) and back processing (extrusion, calendering, cement mixing and rubberized fabrics operations). Mortality rates for all processing workers combined and for men in each section were compared with rates for U.S. White males or for workers employed in other divisions of the same plant. Compared with either referent group, men in the processing division had increased mortality from leukemia, emphysema, and cancers of the stomach, large intestine, and biliary passages and liver. An excess number of deaths from stomach and larger intestine cancer was found predominantly among men in the front processing section (33 observed vs. 17.7 expected deaths, based on rates in nonprocessing workers). Increased mortality from leukemia (14 observed vs. 7.3 expected) and from emphysema (22 observed vs. 11.0 expected) was present among men employed in the back processing section. Examination of mortality from these causes according to age and the year starting work, duration of employment, and years since starting work in the relevant sections of the processing division suggested that observed excesses of stomach cancer, large intestine cancer, leukemia, and emphysema among processing workers are related to occupational exposures. These results are consistent with the findings of studies of other groups of rubber workers.

  7. The Effect of Mortality Shocks on the Age-Pattern of Adult Mortality

    DEFF Research Database (Denmark)

    Zarulli, Virginia

    2013-01-01

    This article aims to investigate the effect of sudden changes in external conditions on human mortality levels and age-patterns. Although several studies have analysed shocking events such as famines or deportations, a systematic assessment of the effect of the shock on the rate of mortality...

  8. Social Capital and Human Mortality: Explaining the Rural Paradox with County-Level Mortality Data

    Science.gov (United States)

    Yang, Tse-Chuan; Jensen, Leif; Haran, Murali

    2011-01-01

    The "rural paradox" refers to standardized mortality rates in rural areas that are unexpectedly low in view of well-known economic and infrastructural disadvantages there. We explore this paradox by incorporating social capital, a promising explanatory factor that has seldom been incorporated into residential mortality research. We do so while…

  9. Stochastic portfolio specific mortality and the quantification of mortality basis risk

    NARCIS (Netherlands)

    R. Plat

    2009-01-01

    In the last decade a vast literature on stochastic mortality models has been developed. However, these models are often not directly applicable to insurance portfolios because: (a) For insurers and pension funds it is more relevant to model mortality rates measured in insured amounts instead of meas

  10. Nutrient enrichment increases mortality of mangroves.

    Directory of Open Access Journals (Sweden)

    Catherine E Lovelock

    Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

  11. Education and Cause-specific Mortality

    DEFF Research Database (Denmark)

    Nordahl, Helene; Lange, Theis; Osler, Merete;

    2014-01-01

    BACKGROUND: Differential exposures to behavioral risk factors have been shown to play an important mediating role on the education-mortality relation. However, little is known about the extent to which educational attainment interacts with health behavior, possibly through differential...... vulnerability. METHODS: In a cohort study of 76,294 participants 30 to 70 years of age, we estimated educational differences in cause-specific mortality from 1980 through 2009 and the mediating role of behavioral risk factors (smoking, alcohol intake, physical activity, and body mass index). With the use...... of marginal structural models and three-way effect decomposition, we simultaneously regarded the behavioral risk factors as intermediates and clarified the role of their interaction with educational exposure. RESULTS: Rate differences in mortality comparing participants with low to high education were 1...

  12. Leisure Time Physical Activity and Mortality

    DEFF Research Database (Denmark)

    Johnsen, Nina Føns; Ekblond, Annette; Thomsen, Birthe Lykke

    2013-01-01

    BACKGROUND: Some studies indicate that a large part of the beneficial effect of physical activity on mortality is confined to a threshold effect of participation. METHODS: Self-reported physical activity was investigated in relation to all-cause mortality in the Danish Diet, Cancer and Health...... cohort, including 29,129 women and 26,576 men aged 50-64 years at baseline 1993-1997. Using Cox proportional hazards models we investigated the associations between mortality rate and leisure time physical activity by exploring 1) participation (yes/no) in each type of activity; 2) a simple dose...... in specific leisure time physical activities, but not with more time spent on those activities. This could suggest that avoiding a sedative lifestyle is more important than a high volume of activity. Nonparticipation in these types of physical activity may be considered as risk factors....

  13. Maternal Mortality in Women with Epilepsy

    LENUS (Irish Health Repository)

    Holohan, M

    2016-10-01

    It is estimated that, in Ireland, there are 10,000 women with epilepsy of childbearing potential1. In this paper the maternal mortality rate for women with epilepsy attending the Rotunda Hospital Epilepsy Clinic 2004 - 2013 was determined. There were 3 maternal deaths in women with epilepsy during this time, which represents a mortality rate of 0.8%. In those women who died, there were concerns in relation to risks to the foetus by taking Anti-Epileptic Drugs (AED) and also issues with access to neurology services before pregnancy, acceptance of specialist support and lack of consistency in advice from health care professionals outside of Ireland. Implementing the nationally agreed care plan for women with epilepsy will improve the quality of care given and potentially we will see a reduction in maternal mortality in these women.

  14. Nutrient Enrichment Increases Mortality of Mangroves

    Science.gov (United States)

    Lovelock, Catherine E.; Ball, Marilyn C.; Martin, Katherine C.; C. Feller, Ilka

    2009-01-01

    Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients. PMID:19440554

  15. The association between depression and mortality

    DEFF Research Database (Denmark)

    Christensen, Gunhild Tidemann; Maartensson, Solvej; Osler, Merete

    2017-01-01

    on depression, use of antidepressants and the Major Depression Inventory (MDI) from a survey in 2004, in which 58.8% (n=6292) of the men participated. Information on mortality and cause of death was retrieved from registers for the period between 2004 and 2011. RESULTS: Depression diagnosis from hospital...... registers as well as self-reported depression, use of antidepressants and having a high MDI-score were significantly associated with mortality from all, natural and unnatural causes. The associations were of a similar magnitude for the register-based measure of depression and for the survey-based measures......BACKGROUND: A number of studies have associated depression with a high mortality risk. However, in surveys, depression is often measured by self-reports in selected sub-samples, while register studies have been based on hospital diagnosis or purchase of antidepressants. We examined how different...

  16. Maternal Mortality Among Migrants in Western Europe

    DEFF Research Database (Denmark)

    Pedersen, Grete Skøtt; Grøntved, Anders; Mortensen, Laust Hvas;

    2013-01-01

    To examine whether an excess risk of maternal mortality exists among migrant women in Western Europe. We searched electronic databases for studies published 1970 through 2013 for all observational studies comparing maternal mortality between the host country and a defined migrant population....... Compared with indigenous born women, the pooled risk estimate (RR) was 2.00 with 95 % confidence interval (CI) of 1.72, 2.33. Migrant women had a non-significantly higher risk of dying from direct than indirect death causes; pooled RRs of 2.65 CI 1.88, 3.74 and 1.83 CI 1.37, 2.45. This meta......-analysis provides evidence that migrant women in Western European countries have an excess risk of maternal mortality....

  17. Estimating mortality due to cigarette smoking

    DEFF Research Database (Denmark)

    Brønnum-Hansen, H; Juel, K

    2000-01-01

    We estimated the mortality from various diseases caused by cigarette smoking using two methods and compared the results. In one method, the "Prevent" model is used to simulate the effect on mortality of the prevalence of cigarette smoking derived retrospectively. The other method, suggested by R....... Peto et al (Lancet 1992;339:1268-1278), requires data on mortality from lung cancer among people who have never smoked and among smokers, but it does not require data on the prevalence of smoking. In the Prevent model, 33% of deaths among men and 23% of those among women in 1993 from lung cancer......, chronic bronchitis, emphysema, ischemic heart disease, and stroke were caused by cigarette smoking. In the method proposed by Peto et al, 35% of deaths among men and 25% of deaths among women from these causes were estimated to be attributable to cigarette smoking. The differences between the two methods...

  18. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    on the relationship between liver cirrhosis mortality and alcohol consumption is included. The conclusion is that the total level of alcohol consumption as well as the specific beverages - beer, wine and spirits - contributes to liver cirrhosis mortality, but the present study also reveals that directly addressing......Empirical evidence gives strong support to a close association between liver cirrhosis mortality and the intake of alcohol and most often a log-linear relationship is assumed in the econometric modeling. The present analysis investigates for unit roots in a panel data set for sixteen European...... countries - covering the period 1970-2006 - where both alcohol consumption and liver cirrhosis seem best described as trend-stationary variables. Therefore a fixed effects model including individual trends is applied in the analysis but also a more flexible non-linear functional form with fewer restrictions...

  19. Mortality in Schizophrenia: Clinical and Serological Predictors

    Science.gov (United States)

    Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Schroeder, Jennifer; Khushalani, Sunil; Yolken, Robert

    2014-01-01

    Persons with schizophrenia have a reduced life expectancy largely due to death from natural causes. Factors that have been previously associated with excess mortality include cigarette smoking and antipsychotic medication. The role of other environmental factors such as exposure to infectious agents has been the subject of only limited investigation. We prospectively assessed a cohort of persons with schizophrenia with a clinical evaluation and a blood sample from which antibodies to human herpes viruses and Toxoplasma gondii were measured. Mortality was determined with data from the National Death Index following a period of up to 11 years. We examined the role of demographic, serological, and clinical factors on mortality. A total of 25 (5%) of 517 persons died of natural causes. The standardized mortality ratio was 2.80 (95% CI 0.89, 6.38). After adjusting for age and gender, mortality from natural causes was predicted in separate models by cigarette smoking (relative risk [RR] = 4.66, P = .0029); lower cognitive score (RR = 0.96, P = .013); level of antibodies to Epstein–Barr virus (RR = 1.22, P = .0041) and to Herpes Simplex virus type 1 (RR = 1.19, P = .030); immunologic disease (RR = 3.14, P = .044); and genitourinary disease (RR = 2.70; P = .035). Because cigarette smoking confers an almost 5-fold risk of mortality, smoking cessation is an urgent priority. Having an elevated level of antibodies to Epstein–Barr virus and to Herpes Simplex virus type 1 are also significant predictors of death from natural causes. PMID:23943410

  20. Estimating spatial inequalities of urban child mortality

    Directory of Open Access Journals (Sweden)

    John R. Weeks

    2013-01-01

    Full Text Available BACKGROUND Recent studies indicate that the traditional rural-urban dichotomy pointing to cities as places of better health in the developing world can be complicated by poverty differentials. Knowledge of spatial patterns is essential to understanding the processes that link individual demographic outcomes to characteristics of a place. A significant limitation, however, is the lack of spatial data and methods that offer flexibility in data inputs. OBJECTIVE This paper tackles some of the issues in calculating intra-urban child mortality by combining multiple data sets in Accra, Ghana and applying a new method developed by Rajaratnam et al. (2010 that efficiently uses summary birth histories for creating local-level measures of under-five child mortality (5q0. Intra-urban 5q0 rates are then compared with characteristics of the environment that may be linked to child mortality. METHODS Rates of child mortality are calculated for 16 urban zones within Accra for birth cohorts from 1987 to 2006. Estimates are compared to calculated 5q0 rates from full birth histories. 5q0 estimates are then related to zone measures of slum characteristics, housing quality, health facilities, and vegetation using a simple trendline R2 analysis. RESULTS Results suggest the potential value of the Rajaratnam et al. method at the micro-spatial scale. Estimated rates indicate that there is variability in child mortality between zones, with a spread of up to 50 deaths per 1,000 births. Furthermore, there is evidence that child mortality is connected to environmental factors such as housing quality, slum-like conditions, and neighborhood levels of vegetation.

  1. Estimating mortality due to cigarette smoking

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Juel, K

    2000-01-01

    We estimated the mortality from various diseases caused by cigarette smoking using two methods and compared the results. In one method, the "Prevent" model is used to simulate the effect on mortality of the prevalence of cigarette smoking derived retrospectively. The other method, suggested by R......, chronic bronchitis, emphysema, ischemic heart disease, and stroke were caused by cigarette smoking. In the method proposed by Peto et al, 35% of deaths among men and 25% of deaths among women from these causes were estimated to be attributable to cigarette smoking. The differences between the two methods...

  2. Adult mortality and children's transition into marriage

    Directory of Open Access Journals (Sweden)

    Sofya Krutikova

    2008-09-01

    Full Text Available Adult mortality due to HIV/AIDS and other diseases is posited to affect children through a number of pathways. On top of health and education outcomes, adult mortality can have significant effects on children by influencing demographic outcomes including the timing of marriage. This paper examines marriage outcomes for a sample of children interviewed in Tanzania in the early 1990s and re-interviewed in 2004. We find that while girls who became paternal orphans married at significantly younger ages, orphanhood had little effect on boys. On the other hand, non-parental deaths in the household affect the timing of marriage for boys.

  3. Sex differences in mortality by ethnic background

    DEFF Research Database (Denmark)

    Oksuzyan, Anna; Drefahl, Sven; Jacobsen, Rune

    2016-01-01

    migrant effect and predominantly male migration from non-Western countries to Denmark and Sweden in 1960-70s, as well as high fertility in their female spouses, we expect to find even smaller sex differential mortality among migrants than in the ethnic Danish and Swedish populations. We use high....... In this study we address whether the substantial differences in the gender gap that are observed between countries can also be observed for different immigrant groups. Previous research has indicated that migrants enjoy better health and lower mortality compared with the host population. Considering the healthy...

  4. Pattern of mortality among Danish thorotrast patients

    DEFF Research Database (Denmark)

    Andersson, Michael; Juel, K; Storm, Hans Henrik

    1993-01-01

    The mortality pattern among 999 Danish patients who had been subjected to angiography of the carotid artery with the alpha-ray emitting X-ray contrast media Thorotrast during the period 1935-47 was assessed by record linkage with the National Death Registry through 1989. Standardized mortality...... neurological conditions and by diseases known to be induced by Thorotrast (cirrhosis and cancer of the liver, leukaemia and other haematological diseases), and it is suggested that unspecific effects induced by the alpha-radiation of Thorotrast may have contributed....

  5. Cognitive impairment and mortality among nonagenarians

    DEFF Research Database (Denmark)

    Andersen, Kjeld; Nybo, Hanne; Gaist, David;

    2002-01-01

    the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox...... regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence...

  6. Changing mortality and average cohort life expectancy

    DEFF Research Database (Denmark)

    Schoen, Robert; Canudas-Romo, Vladimir

    2005-01-01

    of survivorship. An alternative aggregate measure of period mortality which has been seen as less sensitive to period changes, the cross-sectional average length of life (CAL) has been proposed as an alternative, but has received only limited empirical or analytical examination. Here, we introduce a new measure......, the average cohort life expectancy (ACLE), to provide a precise measure of the average length of life of cohorts alive at a given time. To compare the performance of ACLE with CAL and with period and cohort life expectancy, we first use population models with changing mortality. Then the four aggregate...

  7. Source tracing and epidemiological characteristics of a cutaneous anthrax outbreak%一起皮肤炭疽暴发疫情的病源追溯和流行特征分析

    Institute of Scientific and Technical Information of China (English)

    秦怡; 崔荣敏; 郭军巧; 赵卓; 刘大江; 张永刚; 张玉; 董德重; 张立田; 游弋; 刘茹

    2012-01-01

    This study aimed at investigating the epidemiologies! and transmission characteristics of a cutaneous anthrax outbreak among human beings in Liaoning Province in 2011 , and providing scientific basis for prevention and control of cutaneous anthrax . A cross-sectional study was conducted after the outbreak to draw the chain of transmission , and risk factors of the cutaneous anthrax were analyzed . The results showed that the epidemic period of this outbreak was 23 days ; 39 610 persons were investigated , and 158 persons were under medical observation . Thirty-three cases confirmed ho mo logically were distributed in 12 villages and 2 administrative areas of 3 counties ; the male to female ratio was 5 .6 : 1 . Ages of the cases ranged from 16 to 67 . Those aged between 30 and 49 accounted for 78 .4% of the cases . It was suggested that farmers were the mainly af -fected group , accounting for 84 .8% of the total cases . There was a clear transmission chain during the infection process . Results indicated that the cases of this outbreak of cutaneous anthrax were interrelated and caused by exposure at different loca -tions . The infected animals were main sources of infection , and main cause of human anthrax infection was slaughtering infected or died animals or meat contacting , indicating that farmers were at high risk of anthrax infection in Liaoning Province .%目的 通过对2011年发生在辽宁省的一起人间皮肤炭疽暴发疫情的流行病学调查,探讨炭疽疫情的流行特征和传播特点,为防控措施提供依据.方法 采用现况调查方法,绘制传播链,分析致病因素.结果 暴发疫情的流行期为23 d,排查39 610人,医学观察158人,同源确诊病例33例,病例分布于12个自然村和2个管理区,男女发病比为5.6∶1,病例最小16岁,最大67岁,年龄分布集中在30~49岁之间,占78.7%,职业以农民为主,占84.8%,病例感染过程中可见清晰的传播链.结论 本次暴发是一起有关联的

  8. Mortality in people with type 2 diabetes in the UK

    NARCIS (Netherlands)

    Mulnier, H.E.; Seaman, H.E.; Raleigh, V.S.; Soedamah-Muthu, S.S.; Colhoun, H.M.; Lawrenson, R.A.

    2006-01-01

    Aims Under-reporting of diabetes on death certificates contributes to the unreliable estimates of mortality as a result of diabetes. The influence of obesity on mortality in Type 2 diabetes is not well documented. We aimed to study mortality from diabetes and the influence of obesity on mortality in

  9. Aging in the Context of Cohort Evolution and Mortality Selection

    OpenAIRE

    2014-01-01

    This study examines historical patterns of aging through the perspectives of cohort evolution and mortality selection, where the former emphasizes the correlation across cohorts in the age dependence of mortality rates, and the latter emphasizes cohort change in the acceleration of mortality over the life course. In the analysis of historical cohort mortality data, I find support for both perspectives. The rate of demographic aging, or the rate at which mortality accelerates past age 70, is n...

  10. Isolation and identification of bacillus species from soil samples in anthrax epidemic area%炭疽高发地区土壤样本中常见芽胞杆菌的分离及鉴定

    Institute of Scientific and Technical Information of China (English)

    张慧娟; 魏建春; 张恩民; 张建华

    2012-01-01

    Objective To isolate and identify bacillus species in soil samples in anthrax epidemic area and evaluate the disinfection effect and understand the distributions of common bacillus species in the area. Methods Sixty soil samples were collected from the anthrax epidemic area to isolate and identify related bacillus species with PCR assay. Results No Bacillus anthracis was identified, but 13 strains of Bacillus licheniformis, 8 strains of Bacillus subtilis, 11 strains of Bacillus pumilus and 1 strain of Bacillus cereus were identified in 33 gene fragments from 48 clones by sequencing and blast alignment. The specificities of the primers for Bacillus megatherium and Bacillus circulans were not high. Conclusion The disinfection effect in the anthrax epidemic area was good. The related bacillus species exist widely in the soil, suggesting that their identifications are needed in anthrax surveillance by specific genes amplification%目的 通过分离鉴定炭疽可疑污染土壤样本的芽胞杆菌,评价消毒效果和了解监测地区土壤中的芽胞杆菌分布情况.方法 采集炭疽监测点土壤样本60份,对炭疽芽胞杆菌和其他芽胞杆菌进行分离培养和聚合酶链反应扩增鉴定.结果 在可疑污染土壤样本中未分离到炭疽芽胞杆菌;从分离到的48个单克隆菌落中扩增到33个目的片段,经测序和blast比对,确定得到地衣芽胞杆菌13株,枯草芽胞杆菌8株,短小芽胞杆菌扩增11株,蜡样芽胞杆菌扩增到1株,巨大芽胞杆菌引物和环状芽胞杆菌引物特异性不好.结论 本研究提示该监测点炭疽疫情消毒效果可信,但需要进一步研究验证;几种芽胞杆菌在土壤中广泛存在,在炭疽监测工作中进行病原体分离时需要加以鉴别,可通过特异基因扩增来辅助检验.

  11. Infant Mortality: Priority for Social Work.

    Science.gov (United States)

    Combs-Orme, Terri

    1987-01-01

    Bemoans the failure of the social work profession to claim infant mortality as a professional priority in spite of evidence of the appropriateness of social work interventions. Stresses social work's role in the reduction of preventable infant deaths. (Author/KS)

  12. Sedentary behavior and residual-specific mortality

    Science.gov (United States)

    Loprinzi, Paul D.; Edwards, Meghan K.; Sng, Eveleen; Addoh, Ovuokerie

    2016-01-01

    Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0.05). There was evidence of an interaction effect between sedentary behavior and total physical activity on residual-specific mortality (Hazard ratiointeraction [HR] = 0.9989; 95% CI: 0.9982-0.9997; P = 0.008). Conclusion: Sedentary behavior was independently associated with residual-specific mortality. However, there was evidence to suggest that residual-specific mortality risk was a function of sedentary behavior and total physical activity. These findings highlight the need for future work to not only examine the association between sedentary behavior and health independent of total physical activity, but evaluate whether there is a joint effect of these two parameters on health.

  13. Gangrenous cholecystitis: mortality and risk factors.

    Science.gov (United States)

    Önder, Akın; Kapan, Murat; Ülger, Burak Veli; Oğuz, Abdullah; Türkoğlu, Ahmet; Uslukaya, Ömer

    2015-02-01

    As a serious complication of cholelithiasis, gangrenous cholecystitis presents greater mortality than noncomplicated cholecystitis. The aim of this study was to specify the risk factors on mortality. 107 consecutive patients who underwent surgery due to gangrenous cholecystitis between January 1997 and October 2011 were investigated retrospectively. The study included 60 (56.1%) females and 47 (43.9%) males, with a mean age of 60.7 ± 16.4 (21-88) years. Cardiovascular diseases were the most frequently accompanying medical issues (24.3%). Thirty-six complications (33.6%) developed in 29 patients, and surgical site infection was proven as the most common. Longer delay time prior to hospital admission, low white blood cell count, presence of diabetes mellitus, higher blood levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin, pericholecystic fluid in abdominal ultrasonography, and conversion from laparoscopic surgery to open surgery were identified as risk factors affecting mortality (P < 0.001, P = 0.001, P = 0.044, P = 0.005, P = 0.049, P = 0.009, P = 0.022, P = 0.011, and P = 0.004, respectively). Longer delay time prior to hospital admission and low white blood cell count were determined as independent risk factors affecting mortality.

  14. A Genetic Analysis of Mortality in Pigs

    DEFF Research Database (Denmark)

    Varona, Luis; Sorensen, Daniel

    2010-01-01

    An analysis of mortality is undertaken in two breeds of pigs: Danish Landrace and Yorkshire. Zero-inflated and standard versions of hierarchical Poisson, binomial, and negative binomial Bayesian models were fitted using Markov chain Monte Carlo (MCMC). The objectives of the study were to investig...

  15. Calprotectin - A Marker of Mortality in COPD?

    DEFF Research Database (Denmark)

    Holmgaard, Dennis B; Mygind, Lone; Titlestad, Ingrid

    2013-01-01

    Abstract Calprotectin comprises more than 45% of the cytosolic content of neutrophil granulocytes. Because pathogenesis, disease activity and disease progression in COPD are believed to be partly dependent of neutrophil driven inflammation we decided to investigate whether plasma level of calprot......Abstract Calprotectin comprises more than 45% of the cytosolic content of neutrophil granulocytes. Because pathogenesis, disease activity and disease progression in COPD are believed to be partly dependent of neutrophil driven inflammation we decided to investigate whether plasma level...... of calprotectin (p-calprotectin) was associated with all-cause mortality in patients with COPD. We measured p-calprotectin in blood samples from 460 patients with moderate to very severe COPD in stable phase. Patients were stratified into three groups according to p-calprotectin level. Outcome measure was all......-cause mortality. Analyses were adjusted for factors known to influence mortality using a Cox regression analysis. We found a time dependent correlation between p-calprotectin levels and mortality during the first 5 years of follow-up. Increasing levels of p-calprotectin were associated with concomitant increases...

  16. Mortality among hourly motor vehicle manufacturing workers.

    Science.gov (United States)

    Delzell, Elizabeth; Brown, David A; Matthews, Robert

    2003-08-01

    We evaluated mortality among 198,245 motor vehicle industry workers during the period of 1973 to 1995. Workers' mortality rates were lower than expected overall (40,131 observed/43,859 expected deaths, standardized mortality ratio [SMR] = 92, CI = 91-92) and for all major cause of death categories except cancer (SMR = 100, CI = 98-102). Mortality rates were higher than expected for lung cancer overall (SMR = 110, CI = 107-113) and among employees in transmission/gear manufacturing (SMR = 121, CI = 112-130), casting operations (SMR = 122, CI = 110-135), engine manufacturing (SMR = 111, CI = 101-123), and vehicle assembly (SMR = 111, CI = 105-117); for stomach cancer in engine manufacturing (SMR = 147, CI = 110-192); and for prostate cancer in casting operations (SMR = 128, CI = 102-158). Excesses of lung cancer in transmission, vehicle assembly, and casting operations and of stomach cancer in engine manufacturing have been observed in other investigations. Further information on employees' occupational exposures and personal attributes is required to clarify the interpretation of these results.

  17. Topical beta-Blockers and Mortality

    NARCIS (Netherlands)

    Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

  18. Incidence, etiology and mortality of cirrhosis

    DEFF Research Database (Denmark)

    Dam Fialla, Annette; Schaffalitzky de Muckadell, Ove B; Touborg Lassen, Annmarie

    2012-01-01

    Knowledge on the prognosis among patients with cirrhosis is mainly based on clinical trials with selected patient groups as well as population-based register studies with suboptimal diagnostic reliability. The aim of the study was to describe incidence, etiology, and mortality of well......-validated cirrhotic cases in a population-based cohort at Funen (population 470,000) between 1996 and 2006....

  19. Premature mortality in Japan due to ozone

    Science.gov (United States)

    Nawahda, Amin; Yamashita, Ken; Ohara, Toshimasa; Kurokawa, Junichi; Ohizumi, Tsuyoshi; Chen, Fang; Akimoto, Hajime

    2013-12-01

    In Japan, all 47 prefectures conduct routine air quality monitoring at 1145 stations throughout the country to assess environmental effects. This study aims to provide a better understanding of possible estimations of premature mortality in Japan caused by exposure to monitored and modeled concentrations of tropospheric ozone during the period from January to December, 2005. The spatial distribution and temporal variation of ozone concentrations were modeled using the Models-3 Community Multiscale Air Quality modeling system coupled with the Regional Emission Inventory in Asia (CMAQ/REAS). Premature mortality caused by exposure to ozone was calculated assuming a relative risk (RR) value of 1.003 [95% Confidence Interval (CI): 1.001-1.004] for concentrations above 35 ppb according to the SOMO35 index (annual Sum of daily maximum 8-h Ozone Means Over 35 ppb) recommended by WHO (2008). Based on CMAQ/REAS simulations, the estimated all-cause premature mortality in 2005 is about 13,000 (95% CI: 4320-17,300) cases. This value is 2.5 times greater than the estimated premature mortality based on monitored ozone concentrations, which is 5220 (95% CI: 1740-6960) cases.

  20. Embryonic mortality in buffalo naturally mated

    Directory of Open Access Journals (Sweden)

    G. Campanile

    2010-02-01

    Full Text Available The aim of this work was to evaluate the incidence of embryonic mortality in three different period of year in buffaloes naturally mated. The trial was carried out in a buffalo farm located in Caserta province between 2000-2006. In this period were registered natural insemination on 200 buffaloes. Pregnancy diagnosis was carried out on Day 30, confirmed on Day 45 and every 15th days until 90 days after natural mating. Buffaloes that were pregnant on Day 30 but not on Day 45 or Day 90 were considered to have undergone embryonic (EM or fetal mortality (FM respectively. EM and FM were 8.8% and 13.4% respectively throughout the experimental period. A high incidence (P<0.01 of FM was found in the transitional period (December-March than in other months of the year. The incidence of embryonic mortality was significantly (P<0.01 higher between 28-60 days of gestation and lower after 71 day of gestation. The higher fetal mortality found in this study could be due the lower serum levels of progesterone normally found in transitional period in buffalo cows.