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.

Anthrax of the eyelids.

Science.gov (United States)

Amraoui, A.; Tabbara, K. F.; Zaghloul, K.

1992-01-01

Anthrax is a disease caused by Bacillus anthracis. The disease affects primarily herbivores including sheep, cattle, horses, and other domestic animals. Humans may rarely be affected. We examined one male and two female patients with a localised itchy erythematous papule of the eyelid. A necrotising ulcer formed in each of the three cases resulting in a black lesion. Scraping in each case showed Gram positive rods and culture grew Bacillus anthracis. All three patients responded to the intravenous administration of penicillin G, and the lesion resolved leaving scars in two cases. Anthrax is a rare disease but should be considered in the differential diagnosis of ulcers or pustules of the eyelids. Images PMID:1486081

Tumor Targeting and Drug Delivery by Anthrax Toxin

Directory of Open Access Journals (Sweden)

Christopher Bachran

2016-07-01

Full Text Available Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

Tumor Targeting and Drug Delivery by Anthrax Toxin.

Science.gov (United States)

Bachran, Christopher; Leppla, Stephen H

2016-07-01

Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.

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.

Human and animal anthrax in Ethiopia: A retrospective record ...

African Journals Online (AJOL)

26,737 animal anthrax cases (human to animal ratio 1:5) were reported from 2009 to 2013 ... respectively) This data analysis revealed that less number of human anthrax cases ..... quality to reach to strong conclusions and recommendations.

2014 Anthrax epidemic in Koubia prefecture, Guinea-Conakry.

Science.gov (United States)

Sow, M S; Boushab, M B; Balde, H; Camara, A; Sako, F B; Traoré, F A; Diallo, M O S; Diallo, M D; Keita, M; Sylla, A O; Tounkara, T M; Cissé, M

2016-11-01

Anthrax disease is an anthropozoonosis caused by a Gram-positive bacterium, Bacillus anthracis. Our objective was to describe the epidemiological, clinical and therapeutic features of the 2014 epidemic in Koubia prefecture. This retrospective study examined all of the anthrax cases reported in Fafaya, Koubia Prefecture. In March and April 2014, there were 39 cases of human anthrax reported, for an incidence of 1.135%. The mean age was 20.9 (± 18.3) with a sex ratio of 2.54 (28/11) in favor of men. Seventy-six percent (23/39) were single. More than one half were students (53.8%). The main clinical signs were fever in 71, 8% (n = 28 /), papules 59% (n = 23), vesicles of 59% (n = 23) Digestive and cutaneous signs represented 35.9 % and 64.1% respectively; 35% had ingested contaminated meat and 17.95% were in direct contact with a sick animal. We didn't find any correlation between the mode of infection and onset of signs. The fatality rate was 28.21%. The 2014 epidemic of anthrax disease in the Koubia prefecture was marked by a high incidence and lethality. Clinical manifestations were cutaneaous and digestive. These results may serve further interventions to fight against anthrax disease. They should mainly focus on an awareness of peasants, surveillance and vaccination of cattle. Other studies seem to be necessary.

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.

Effective antiprotease-antibiotic treatment of experimental anthrax

OpenAIRE

Popov, Serguei G; Popova, Taissia G; Hopkins, Svetlana; Weinstein, Raymond S; MacAfee, Rebecca; Fryxell, Karl J; Chandhoke, Vikas; Bailey, Charles; Alibek, Ken

2005-01-01

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 un...

[Anthrax meningoencephalitis: a case report and review of Turkish literature].

Science.gov (United States)

Metan, Gökhan; Uysal, Burcu; Coşkun, Ramazan; Perçin, Duygu; Doğanay, Mehmet

2009-10-01

The incidence of anthrax is decreasing in Turkey, however, it is still endemic in some regions of the country. Although central nervous system involvement is rare in cases with anthrax, high mortality rates are significant. Here, we report a 46-years old woman who was anthrax meningoencephalitis. The patient was from Yozgat located in Central Anatolia, Turkey. Her history revealed that following peeling the skin of sheeps and consuming their meat a week ago, a lesion developed in her left forearm and she had been treated with penicilin G with the diagnosis of cutaneous anthrax in a local health center. The patient was admitted to the emergency room of our hospital due to increased headache and loss of conciousness and diagnosed as anthrax meningitis. Crytallized penicilin G (24 MU/day IV) and vancomycin (2 g/day IV) were initiated. The macroscopy of cerebrospinal fluid (CSF) sample was haemorrhagic, white blood cell count was 40/mm3 (80% of neutrophil) and Gram staining of CSF yielded abundant gram-positive bacilli. The diagnosis was confirmed by the isolation of Bacillus anthracis from CSF culture. Although the isolate was susceptible to penicillin and dexamethasone was added to the treatment, the patient died. Review of the Turkish literature revealed seven cases of anthrax with central nervous system involvement between 1980-2008. One of the patients was an 11-years old boy and the others were adults aged between 19 and 64 years. The source of the infection was skin in four patients and inhalation in one patient. The most common findings in all of the patients were inhabitance in rural area, haemorrhagic CSF and loss of all patients despite appropriate antibiotic therapy. In conclusion, anthrax meningitis and meningoencephalitis should be considered in the differential diagnosis of haemorrhagic meningitis in areas where anthrax is endemic and high rate of mortality despite appropriate therapy should always be kept in mind.

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...

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.

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.

Modeling the Ecological Niche of Bacillus anthracis to Map Anthrax Risk in Kyrgyzstan.

Science.gov (United States)

Blackburn, Jason K; Matakarimov, Saitbek; Kozhokeeva, Sabira; Tagaeva, Zhyldyz; Bell, Lindsay K; Kracalik, Ian T; Zhunushov, Asankadyr

2017-03-01

AbstractAnthrax, caused by the environmental bacterium Bacillus anthracis , is an important zoonosis nearly worldwide. In Central Asia, anthrax represents a major veterinary and public health concern. In the Republic of Kyrgyzstan, ongoing anthrax outbreaks have been reported in humans associated with handling infected livestock and contaminated animal by-products such as meat or hides. The current anthrax situation has prompted calls for improved insights into the epidemiology, ecology, and spatial distribution of the disease in Kyrgyzstan to better inform control and surveillance. Disease control for both humans and livestock relies on annual livestock vaccination ahead of outbreaks. Toward this, we used a historic database of livestock anthrax reported from 1932 to 2006 mapped at high resolution to develop an ecological niche model-based prediction of B. anthracis across Kyrgyzstan and identified spatial clusters of livestock anthrax using a cluster morphology statistic. We also defined the seasonality of outbreaks in livestock. Cattle were the most frequently reported across the time period, with the greatest number of cases in late summer months. Our niche models defined four areas as suitable to support pathogen persistence, the plateaus near Talas and Bishkek, the valleys of western Kyrgyzstan along the Fergana Valley, and the low-lying areas along the shore of Lake Isyk-Kul. These areas should be considered "at risk" for livestock anthrax and subsequent human cases. Areas defined by the niche models can be used to prioritize anthrax surveillance and inform efforts to target livestock vaccination campaigns.

Potent antitumor activity of a urokinase-activated engineered anthrax toxin

Science.gov (United States)

Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

2003-01-01

The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

DUST-BATHING BEHAVIORS OF AFRICAN HERBIVORES AND THE POTENTIAL RISK OF INHALATIONAL ANTHRAX.

Science.gov (United States)

Barandongo, Zoe R; Mfune, John K E; Turner, Wendy C

2018-01-01

:  Anthrax in herbivorous wildlife and livestock is generally assumed to be transmitted via ingestion or inhalation of Bacillus anthracis spores. Although recent studies have highlighted the importance of the ingestion route for anthrax transmission, little is known about the inhalational route in natural systems. Dust bathing could aerosolize soilborne pathogens such as B. anthracis, exposing dust-bathing individuals to inhalational infections. We investigated the potential role of dust bathing in the transmission of inhalational anthrax to herbivorous wildlife in Etosha National Park, Namibia, an area with endemic seasonal anthrax outbreaks. We 1) cultured soils from dust-bathing sites for the presence and concentration of B. anthracis spores, 2) monitored anthrax carcass sites, the locations with the highest B. anthracis concentrations, for evidence of dust bathing, including a site where a zebra died of anthrax on a large dust bath, and 3) characterized the ecology and seasonality of dust bathing in plains zebra ( Equus quagga), blue wildebeest ( Connochaetes taurinus), and African savanna elephant ( Loxodonta africana) using a combination of motion-sensing camera traps and direct observations. Only two out of 83 dust-bath soils were positive for B. anthracis, both with low spore concentrations (≤20 colony-forming units per gram). We also detected no evidence of dust baths occurring at anthrax carcass sites, perhaps due to carcass-induced changes in soil composition that may deter dust bathing. Finally, despite observing some seasonal variation in dust bathing, preliminary evidence suggests that the seasonality of dust bathing and anthrax mortalities are not correlated. Thus, although dust bathing creates a dramatic cloud of aerosolized soil around an individual, our microbiologic, ecologic, and behavioral results in concert demonstrate that dust bathing is highly unlikely to transmit inhalational anthrax infections.

Military Hospitalizations among Deployed US Service Members Following Anthrax Vaccination, 1998-2001

National Research Council Canada - National Science Library

Wells, Timothy S; Sato, Paul A; Smith, Tyler C; Wang, Linda Z; Reed, Robert J; Kappel Ryan, Margaret A

2006-01-01

.... 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...

Anthrax, People and Dead Hippos

Centers for Disease Control (CDC) Podcasts

2017-11-07

Epidemiologist, Dr. Melissa Marx, discuses anthrax deaths in people who ate dead hippos.  Created: 11/7/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/7/2017.

Soil geochemical parameters influencing the spatial distribution of anthrax in Northwest Minnesota, USA

International Nuclear Information System (INIS)

Nath, Samuel; Dere, Ashlee

2016-01-01

Bacillus anthracis is the pathogenic bacterium that causes anthrax, which dwells in soils as highly resilient endospores. B. anthracis spore viability in soil is dependent upon environmental conditions, but the soil properties necessary for spore survival are unclear. In this study we used a range of soil geochemical and physical parameters to predict the spatial distribution of B. anthracis in northwest Minnesota, where 64 cases of anthrax in livestock were reported from 2000 to 2013. Two modeling approaches at different spatial scales were used to identify the soil conditions most correlated to known anthrax cases using both statewide and locally collected soil data. Ecological niche models were constructed using the Maximum Entropy (Maxent) approach and included 11 soil parameters as environmental inputs and recorded anthrax cases as known presences. One ecological niche model used soil data and anthrax presences for the entire state while a second model used locally sampled soil data (n = 125) and a subset of anthrax presences, providing a test of spatial scale. In addition, simple logistic regression models using the localized soil data served as an independent measure of variable importance. Maxent model results indicate that at a statewide level, soil calcium and magnesium concentrations, soil pH, and sand content are the most important properties for predicting soil suitability for B. anthracis while at the local level, clay and sand content along with phosphorous and strontium concentrations are most important. These results also show that the spatial scale of analysis is important when considering soil parameters most important for B. anthracis spores. For example, at a broad scale, B. anthracis spores may require Ca-rich soils and an alkaline pH, but may also concentrate in microenvironments with high Sr concentrations. The study is also one of the first ecological niche models that demonstrates the major importance of soil texture for defining

Orbito-Maxillofacial Cutaneous Anthrax

African Journals Online (AJOL)

and development of a black eschar were reviewed. Occupational history, falls and/or contact with animal meat was ... and oral ciprofloxacin (500mg BD for 21 days). The culture results isolated Bacillus anthracis highly ... The clinical evolution of cutaneous anthrax is typical with the initial development of minute red macules.

Tumor Targeting and Drug Delivery by Anthrax Toxin

OpenAIRE

Bachran, Christopher; Leppla, Stephen H.

2016-01-01

Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associ...

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).

Monte Carlo N-particle simulation of neutron-based sterilisation of anthrax contamination.

Science.gov (United States)

Liu, B; Xu, J; Liu, T; Ouyang, X

2012-10-01

To simulate the neutron-based sterilisation of anthrax contamination by Monte Carlo N-particle (MCNP) 4C code. Neutrons are elementary particles that have no charge. They are 20 times more effective than electrons or γ-rays in killing anthrax spores on surfaces and inside closed containers. Neutrons emitted from a (252)Cf neutron source are in the 100 keV to 2 MeV energy range. A 2.5 MeV D-D neutron generator can create neutrons at up to 10(13) n s(-1) with current technology. All these enable an effective and low-cost method of killing anthrax spores. There is no effect on neutron energy deposition on the anthrax sample when using a reflector that is thicker than its saturation thickness. Among all three reflecting materials tested in the MCNP simulation, paraffin is the best because it has the thinnest saturation thickness and is easy to machine. The MCNP radiation dose and fluence simulation calculation also showed that the MCNP-simulated neutron fluence that is needed to kill the anthrax spores agrees with previous analytical estimations very well. The MCNP simulation indicates that a 10 min neutron irradiation from a 0.5 g (252)Cf neutron source or a 1 min neutron irradiation from a 2.5 MeV D-D neutron generator may kill all anthrax spores in a sample. This is a promising result because a 2.5 MeV D-D neutron generator output >10(13) n s(-1) should be attainable in the near future. This indicates that we could use a D-D neutron generator to sterilise anthrax contamination within several seconds.

A 2011 Risk/Benefit Analysis of the Anthrax Vaccine Immunization Program

Science.gov (United States)

2011-06-10

filled with botulinum toxin, 10 with anthrax, and 2 with aflatoxin.‖18 In 1992, Ken Alibek, a senior Russian bioweapons program manager defected...William K. Honner, Rosha A. Loach , Cynthia A. Moore, and J. David Erickson. ―Birth Defects Among Infants Born to Women Who Received Anthrax Vaccine In

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest.

Science.gov (United States)

Hoffmann, Constanze; Zimmermann, Fee; Biek, Roman; Kuehl, Hjalmar; Nowak, Kathrin; Mundry, Roger; Agbor, Anthony; Angedakin, Samuel; Arandjelovic, Mimi; Blankenburg, Anja; Brazolla, Gregory; Corogenes, Katherine; Couacy-Hymann, Emmanuel; Deschner, Tobias; Dieguez, Paula; Dierks, Karsten; Düx, Ariane; Dupke, Susann; Eshuis, Henk; Formenty, Pierre; Yuh, Yisa Ginath; Goedmakers, Annemarie; Gogarten, Jan F; Granjon, Anne-Céline; McGraw, Scott; Grunow, Roland; Hart, John; Jones, Sorrel; Junker, Jessica; Kiang, John; Langergraber, Kevin; Lapuente, Juan; Lee, Kevin; Leendertz, Siv Aina; Léguillon, Floraine; Leinert, Vera; Löhrich, Therese; Marrocoli, Sergio; Mätz-Rensing, Kerstin; Meier, Amelia; Merkel, Kevin; Metzger, Sonja; Murai, Mizuki; Niedorf, Svenja; De Nys, Hélène; Sachse, Andreas; van Schijndel, Joost; Thiesen, Ulla; Ton, Els; Wu, Doris; Wieler, Lothar H; Boesch, Christophe; Klee, Silke R; Wittig, Roman M; Calvignac-Spencer, Sébastien; Leendertz, Fabian H

2017-08-02

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

Science.gov (United States)

Hoffmann, Constanze; Zimmermann, Fee; Biek, Roman; Kuehl, Hjalmar; Nowak, Kathrin; Mundry, Roger; Agbor, Anthony; Angedakin, Samuel; Arandjelovic, Mimi; Blankenburg, Anja; Brazolla, Gregory; Corogenes, Katherine; Couacy-Hymann, Emmanuel; Deschner, Tobias; Dieguez, Paula; Dierks, Karsten; Düx, Ariane; Dupke, Susann; Eshuis, Henk; Formenty, Pierre; Yuh, Yisa Ginath; Goedmakers, Annemarie; Gogarten, Jan F.; Granjon, Anne-Céline; McGraw, Scott; Grunow, Roland; Hart, John; Jones, Sorrel; Junker, Jessica; Kiang, John; Langergraber, Kevin; Lapuente, Juan; Lee, Kevin; Leendertz, Siv Aina; Léguillon, Floraine; Leinert, Vera; Löhrich, Therese; Marrocoli, Sergio; Mätz-Rensing, Kerstin; Meier, Amelia; Merkel, Kevin; Metzger, Sonja; Murai, Mizuki; Niedorf, Svenja; de Nys, Hélène; Sachse, Andreas; van Schijndel, Joost; Thiesen, Ulla; Ton, Els; Wu, Doris; Wieler, Lothar H.; Boesch, Christophe; Klee, Silke R.; Wittig, Roman M.; Calvignac-Spencer, Sébastien; Leendertz, Fabian H.

2017-08-01

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation.

Progress and novel strategies in vaccine development and treatment of anthrax.

Science.gov (United States)

Chitlaru, Theodor; Altboum, Zeev; Reuveny, Shaul; Shafferman, Avigdor

2011-01-01

The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis. © 2010 John Wiley & Sons A/S.

Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

Science.gov (United States)

Scobie, Heather M; Wigelsworth, Darran J; Marlett, John M; Thomas, Diane; Rainey, G. Jonah A; Lacy, D. Borden; Manchester, Marianne; Collier, R. John; Young, John A. T

2006-01-01

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. PMID:17054395

Micromotors to capture and destroy anthrax simulant spores.

Science.gov (United States)

Orozco, Jahir; Pan, Guoqing; Sattayasamitsathit, Sirilak; Galarnyk, Michael; Wang, Joseph

2015-03-07

Towards addressing the need for detecting and eliminating biothreats, we describe a micromotor-based approach for screening, capturing, isolating and destroying anthrax simulant spores in a simple and rapid manner with minimal sample processing. The B. globilli antibody-functionalized micromotors can recognize, capture and transport B. globigii spores in environmental matrices, while showing non-interactions with excess of non-target bacteria. Efficient destruction of the anthrax simulant spores is demonstrated via the micromotor-induced mixing of a mild oxidizing solution. The new micromotor-based approach paves a way to dynamic multifunctional systems that rapidly recognize, isolate, capture and destroy biological threats.

Defining Moments in MMWR History: CDC's Response to Intentional Release of Anthrax - 2001

Centers for Disease Control (CDC) Podcasts

On October 4, 2001, shortly after the September 11 attacks in New York City and Washington, DC, the Palm Beach County Health Department, the Florida State Department of Health, and CDC reported a case of anthrax in a 63-year-old man from Florida. This case was first reported in MMWR and marked the beginning of a series of anthrax cases that resulted from intentional delivery of Bacillus anthracis spores sent through the mail. In this podcast, Dr. Sherif Zaki recalls CDC's investigation and response to the anthrax attacks.

Detailed Safety Review of Anthrax Vaccine Adsorbed

National Research Council Canada - National Science Library

2001-01-01

To date, 18 human studies have assessed the safety of anthrax vaccination. These studies, some stretching back almost 50 years, reported adverse events after vaccination in varying degrees of detail...

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

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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.

Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.

Science.gov (United States)

Kracalik, Ian T; Kenu, Ernest; Ayamdooh, Evans Nsoh; Allegye-Cudjoe, Emmanuel; Polkuu, Paul Nokuma; Frimpong, Joseph Asamoah; Nyarko, Kofi Mensah; Bower, William A; Traxler, Rita; Blackburn, Jason K

2017-10-01

Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF) models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805 (95% CI: 519, 890) thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.

Directory of Open Access Journals (Sweden)

Ian T Kracalik

2017-10-01

Full Text Available Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5 million livestock and 805 (95% CI: 519, 890 thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

Effective antiprotease-antibiotic treatment of experimental anthrax

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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

Cutaneous anthrax in the northeast of Iran: A case report and review of the literature

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Mohsen Karbalaei Zadeh Babaki

2018-02-01

Full Text Available Bacillus anthracis is an aerobic, gram-positive, and spore-forming Bacillus species. The most common form of anthrax infection is the cutaneous form. The infection usually develops several days after exposure to products of infected animals and manifest as black sore with severe swelling on the skin.A 52-year-old female with a black and swollen lesion on her index finger presented to Ghaem Hospital, Mashhad, Iran, in October 2015. Biopsy and swab culture were performed immediately. Cutaneous anthrax was characterized by microscopic examination of B. anthracis spore using Gram staining. The patient was then treated with antibiotics after diagnosis.According to the reports of Provincial Health Center of Khorasan Razavi, northeast of Iran, no cases of anthrax have been reported in humans since 2013. There were neither occupational risk factors, nor any routine predisposing factors for acquiring anthrax in this woman. Although this patient is the first case reported with cutaneous anthrax since the past three years, two cases of sheep anthrax have been reported in Khorasan Razavi Province during 2013-2015. This patient had a history of contact with the skull of a slaughtered sheep. The patient was treated after making correct and rapid diagnosis and sufficient antibiotic therapy.

Historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon.

Science.gov (United States)

D'Amelio, Enrico; Gentile, Bernardina; Lista, Florigio; D'Amelio, Raffaele

2015-12-01

Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. anthracis has been considered the most serious bioterrorism agent for a long time. During the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. Several factors may mitigate the consequences of an anthrax attack, including 1. the capability to promptly recognize and manage the illness and its public health consequences; 2. the limitation of secondary contamination risk through an appropriate decontamination; and 3. the evolution of genotyping methods (for microbes characterization at high resolution level) that can influence the course and/or focus of investigations, impacting the response of the government to an attack. A PubMed search has been done using the key words “bioterrorism anthrax”. Over one thousand papers have been screened and the most significant examined to present a comprehensive literature review in order to discuss the current knowledge and strategies in preparedness for a possible deliberate release of B. anthracis spores and to indicate the most current and complete documents in which to deepen. The comprehensive analysis of the two most relevant unnatural anthrax release events, Sverdlovsk in the former Soviet Union (1979) and the contaminated letters in the USA (2001), shows that inhalational anthrax may easily and cheaply be spread resulting in serious consequences. The damage caused by an anthrax attack can be limited if public health organization, first responders, researchers and investigators will be able to promptly manage anthrax cases and use new technologies for decontamination methods and in forensic microbiology.

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

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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.

Evaluation of cutaneous anthrax cases during an outbreak in the east region of Turkey.

Science.gov (United States)

Kural Ünüvar, Esra; Akgün Karapınar, Deniz Bahar; Dizen Namdar, Nazlı

2016-11-17

Anthrax is a zoonotic infection caused by Bacillus anthracis. We aimed to retrospectively evaluate cutaneous anthrax cases that occurred during an outbreak in eastern Turkey (Hakkari-Yüksekova), where people mostly earn their living from animal husbandry. Forty-six cutaneous anthrax patients that were admitted to the hospital during a very short duration of 3 months (June-August 2011) were evaluated. Out of 46 patients, 27 (52%) were women and 19 (48%) were men. The mean age was 37 ± 13 years. The distribution of occupations was 1 butcher, 1 cook, 5 farmers, 27 housewives, 11 shepherds, and 1 teacher. Multiple lesions were seen in 7 patients (15%) and the rest of the patients had only 1 lesion. We observed significant clinical differences among the cases and noted which particular symptoms were associated with the various skin lesions. We treated our patients with intramuscular procaine penicillin or oral ciprofloxacin/doxycycline. Anthrax is an important health problem that can cause lethal outbreaks. Therefore, one should think about anthrax when faced with a patient with history of animal contact that has a painless ulcer with edema and/or vesicles, especially in endemic countries like Turkey.

Awareness and attitudes towards anthrax and meat consumption practices among affected communities in Zambia: A mixed methods approach.

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Doreen Chilolo Sitali

2017-05-01

Full Text Available In Zambia, human anthrax cases often occur following cases of animal anthrax. Human behaviour has been implicated in this transmission. The objective of the study was to explore human behavioural patterns that may contribute to outbreaks of anthrax among affected communities.A mixed methods study was conducted in four districts of Zambia from November 2015 to February 2016. A cross sectional survey involving 1,127 respondents, six focus group discussions and seven key informant interviews with professional staff were conducted. Descriptive statistics on socio-demographic characteristics, awareness of anthrax, attitudes towards cattle vaccination and risk factors for anthrax and vaccination practices were run using STATA 12 for analysis.Overall, 88% of respondents heard about anthrax, 85.1% were aware that anthrax is transmitted by eating infected meat and 64.2% knew that animals and humans can be infected with anthrax. However, qualitative data suggested that awareness of anthrax varied across communities. Qualitative findings also indicated that, in Western and Muchinga provinces, human anthrax was transmitted by eating infected beef and hippo (Hippopotamus amphibious meat, respectively. Although survey data indicated that 62.2% of respondents vaccinated their animals, qualitative interviews and annual vaccination reports indicated low vaccination rates, which were attributed to inadequate veterinary service provision and logistical challenges. While 82% of respondents indicated that they reported animal deaths to veterinary officers, only 13.5% of respondents buried infected carcasses. Majority (78.1% of respondents either ate, sold or shared meat from dead animals with other community members. Poverty, lack of access to meat protein and economic reasons were cited as drivers for consuming infected meat.Health education campaigns must be intensified to reduce the risk of human exposure. Veterinary extension services should be strengthened and

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

International Nuclear Information System (INIS)

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

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

Anthrax does not forgive mistakes: the information assessment following the yamal peninsula outbreak in the summer of 2016

Directory of Open Access Journals (Sweden)

I. V. Shestakova

2017-01-01

Full Text Available For the first time in a long time period the sources of actual information about anthrax in Russia and in the world are systematized. The essence of the problem, features of epidemiology and clinical manifestations of the current forms of anthrax disease are analyzed. The upgraded classification of anthrax is presented, the clinical manifestations of oro-oropharyngeal varieties of intestinal form and injectable form of anthrax are described, according to extensive literature data and international guidelines and recommendations. The recommendations for clinical management of patients and diagnosis of disease are given. The need for strict compliance to the vaccination requirements of anthrax among animals and persons from risk groups is proven.

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.

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

The Disulfide Bond Cys255-Cys279 in the Immunoglobulin-Like Domain of Anthrax Toxin Receptor 2 Is Required for Membrane Insertion of Anthrax Protective Antigen Pore.

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Pedro Jacquez

Full Text Available Anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, pH-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. We previously reported that reduction of the disulfide bonds in the immunoglobulin-like (Ig domain of the anthrax toxin receptor 2 (ANTXR2 inhibited the function of the protective antigen (PA pore. In the present study, the disulfide linkage in the Ig domain was identified as Cys255-Cys279 and Cys230-Cys315. Specific disulfide bond deletion mutants were achieved by replacing Cys residues with Ala residues. Deletion of the disulfide bond C255-C279, but not C230-C315, inhibited the PA pore-induced release of the fluorescence dyes from the liposomes, suggesting that C255-C279 is essential for PA pore function. Furthermore, we found that deletion of C255-C279 did not affect PA prepore-to-pore conversion, but inhibited PA pore membrane insertion by trapping the PA membrane-inserting loops in proteinaceous hydrophobic pockets. Fluorescence spectra of Trp59, a residue adjacent to the PA-binding motif in von Willebrand factor A (VWA domain of ANTXR2, showed that deletion of C255-C279 resulted in a significant conformational change on the receptor ectodomain. The disulfide deletion-induced conformational change on the VWA domain was further confirmed by single-particle 3D reconstruction of the negatively stained PA-receptor heptameric complexes. Together, the biochemical and structural data obtained in this study provides a mechanistic insight into the role of the receptor disulfide bond C255-C279 in anthrax toxin action. Manipulation of the redox states of the receptor, specifically targeting to C255-C279, may become a novel strategy to treat anthrax.

Anthrax and the Geochemistry of Soils in the Contiguous United States

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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.

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.

Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism.

Science.gov (United States)

Kahan, Ernesto; Fogelman, Yacov; Kitai, Eliezer; Vinker, Shlomo

2003-08-01

The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.

Small molecule inhibitors of anthrax edema factor.

Science.gov (United States)

Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; O'Malley, Sean; Leppla, Stephen H; Johnson, Alan T

2018-01-15

Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

OpenAIRE

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

2012-01-01

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

The anthrax vaccine: is it safe? does it work?

National Research Council Canada - National Science Library

Committee to Assess the Safety and Efficacy of the Anthrax Vaccine, Medical Follow-Up Agency

2002-01-01

...), was licensed in 1970. It was initially used to protect people who might be exposed to anthrax where they worked, such as veterinarians and textile plant workers who process animal hair. When the U...

Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine.

Science.gov (United States)

Keitel, Wendy A

2006-08-01

Recent terrorist attacks involving the use of Bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. Studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. The most promising vaccine candidates contain purified recombinant protective antigen. Clinical trials of one of these, recombinant protective antigen (rPA)102, are underway. Initial results suggest that rPA102 is well tolerated and immunogenic. Additional trials are necessary to identify optimal formulations and immunization regimens for pre- and postexposure prophylaxis. Future licensure of these and other candidate vaccines will depend on their safety and immunogenicity profiles in humans, and their ability to confer protection in animal models of inhalational anthrax.

Defining Moments in MMWR History: CDC’s Response to Intentional Release of Anthrax - 2001

Centers for Disease Control (CDC) Podcasts

2017-10-12

On October 4, 2001, shortly after the September 11 attacks in New York City and Washington, DC, the Palm Beach County Health Department, the Florida State Department of Health, and CDC reported a case of anthrax in a 63-year-old man from Florida. This case was first reported in MMWR and marked the beginning of a series of anthrax cases that resulted from intentional delivery of Bacillus anthracis spores sent through the mail. In this podcast, Dr. Sherif Zaki recalls CDC’s investigation and response to the anthrax attacks.  Created: 10/12/2017 by MMWR.   Date Released: 10/12/2017.

Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

National Research Council Canada - National Science Library

Brittingham, Katherine C; Ruthel, Gordon; Panchal, Rekha G; Fuller, Claudette L; Ribot, Wilson J

2005-01-01

Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhaled anthrax because they initiate germination and dissemination of spores...

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): anthrax

DEFF Research Database (Denmark)

EFSA Panel on Animal Health and Welfare; More, Simon J.; Bøtner, Anette

2017-01-01

Anthrax has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of anthrax to be listed, Article 9 for the categorisation of anthrax according to disease prevention and control rul...... species to be listed for anthrax according to Article 8(3) are several species of mammals, birds and reptiles, and susceptible herbivores and pigs as reservoir....

[Properties of live antibiotics-resistant anthrax vaccine STI-PR after long-term storage].

Science.gov (United States)

Aksenova, L Iu; Buravtseva, N P; Kogotkova, O I; Eremenko, E I; Tsygankova, O I

2007-01-01

Study showed that cultural, morphologic, genetic, immunologic characteristics, and resistance to antibiotics of STI-PR anthrax vaccine did not change after storage during 20 years in lyophilized condition. It has been shown that medium for lyophilization plays important role in preservation of vitality of anthrax spores. Optimal preservative properties have been observed for thioureal and sucrose-gelatinous media for lyophilization. Obtained results give reasons for prolongation of shelf live of STI-PR vaccine from 2 - 3 to 5 - 8 years.

A Viral Nanoparticle with Dual Function as an Anthrax Antitoxin and Vaccine

Science.gov (United States)

Manayani, Darly J; Thomas, Diane; Dryden, Kelly A; Reddy, Vijay; Siladi, Marc E; Marlett, John M; Rainey, G. Jonah A; Pique, Michael E; Scobie, Heather M; Yeager, Mark; Young, John A. T; Manchester, Marianne; Schneemann, Anette

2007-01-01

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. PMID:17922572

Crystallization and preliminary X-ray analysis of the vWA domain of human anthrax toxin receptor 1

International Nuclear Information System (INIS)

Cai, Chenguang; Zhao, Ying; Tong, Xiaohang; Fu, Sheng; Li, Yuanyuan; Wu, Yang; Li, Xumei; Lou, Zhiyong

2010-01-01

The vWA domain of human anthrax toxin receptor 1 was overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 1.8 Å resolution. The Gram-positive spore-forming bacterium Bacillus anthracis causes anthrax by secreting anthrax toxin, which consists of protective antigen (PA), lethal factor and oedema factor. Binding of PA to receptors triggers the multi-step process of anthrax toxin entry into target cells. Two distinct cellular receptors, ANTXR1 (also known as tumour endothelial marker 8; TEM8) and ANTXR2 (also known as capillary morphogenesis protein 2; CMG2), for anthrax toxin have been identified. Although the crystal structure of the extracellular von Willebrand factor A (vWA) domain of CMG2 has been reported, the difference between the vWA domains of TEM8 and CMG2 remains unclear because there are no structural data for the TEM8 vWA domain. In this report, the TEM8 vWA domain was expressed, purified and crystallized. X-ray diffraction data were collected to 1.8 Å resolution from a single crystal, which belonged to space group P1 with unit-cell parameters a = 65.9, b = 66.1, c = 74.4 Å, α = 63.7, β = 88.2, γ = 59.9°

Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

Science.gov (United States)

Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

2012-01-01

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. PMID:22511955

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.

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.

False alarms, real challenges--one university's communication response to the 2001 anthrax crisis.

Science.gov (United States)

Clarke, Christopher E; Chess, Caron

2006-01-01

Considerable research exists on how government agencies at the federal, state, and local levels communicated during the fall 2001 anthrax attacks. However, there is little research on how other institutions handled this crisis, in terms of their response to potential anthrax contamination (aka "white powder scares") and their approach to disseminating important health and safety information. In this article, we investigate a major university's communication response to the anthrax crisis. First, we describe its communication experiences relating to a large white powder scare that occurred in October 2001. Second, we describe the university's broader communication efforts in terms of several important elements of risk communication research, including influence of source attributes, key messages, preferred channels, responses to information requests, and organizational influences. This study underlines that an institution does not have to be directly affected by a crisis to find itself on the communication "front lines." Moreover, other institutions may find it useful to learn from the experiences of this university, so that they may communicate more effectively during future crises.

The anthrax vaccine and research: reactions from postal workers and public health professionals.

Science.gov (United States)

Quinn, Sandra Crouse; Thomas, Tammy; Kumar, Supriya

2008-12-01

During the 2001 anthrax attacks, public health agencies faced operational and communication decisions about the use of antibiotic prophylaxis and the anthrax vaccine with affected groups, including postal workers. This communication occurred within an evolving situation with incomplete and uncertain data. Guidelines for prophylactic antibiotics changed several times, contributing to confusion and mistrust. At the end of 60 days of taking antibiotics, people were offered an additional 40 days' supply of antibiotics, with or without the anthrax vaccine, the former constituting an investigational new drug protocol. Using data from interviews and focus groups with 65 postal workers in 3 sites and structured interviews with 16 public health professionals, this article examines the challenges for public health professionals who were responsible for communication with postal workers about the vaccine. Multiple factors affected the response, including a lack of trust, risk perception, disagreement about the recommendation, and the controversy over the military's use of the vaccine. Some postal workers reacted with suspicion to the vaccine offer, believing that they were the subjects of research, and some African American workers specifically drew an analogy to the Tuskegee syphilis study. The consent forms required for the protocol heightened mistrust. Postal workers also had complex and ambivalent responses to additional research on their health. The anthrax attacks present us with an opportunity to understand the challenges of communication in the context of uncertain science and suggest key strategies that may improve communications about vaccines and other drugs authorized for experimental use in future public health emergencies.

[Anthrax in the canton of Zurich between 1878 and 2005].

Science.gov (United States)

Brandes Ammann, A; Brandl, H

2007-07-01

Historical records reporting cases of animal anthrax in the canton of Zurich between 1878 and 2005 were analysed on the level of political communities regarding occurrence and number of cases, animals affected, and number of communities affected. Data were correlated with industrial activities (tanning, wool and horse hair processing) in a community and to the prevailing meteorological conditions. A total of 830 cases of animal anthrax has been recorded in 140 of 171 communities. Occurrence correlated with industrial activities in a community such as companies handling potentially contaminated materials (hides, fur, wool, hair, meat, or bone meal). The influence of wool processing companies (P = 0. 004) and tanneries (P = 0. 032) was significant whereas horse hair processing had no effect. However, a statistical relationship between the number of cases reported and meteorological data (rainfall, mean temperature) was not found.

Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax

Directory of Open Access Journals (Sweden)

Anshu Malik

2018-03-01

Full Text Available Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP. Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF of Bacillus anthracis, the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable. In this context, we have evaluated the potential of various vaccine formulations comprising of protective antigen (PA encapsulated trimethyl-chitosan nanoparticles (TMC-PA in conjunction with either CpG-C ODN 2395 (CpG or Poly I:C. Each formulation was administered via three different routes, viz., subcutaneous (SC, intramuscular (IM, and intraperitoneal in female BALB/c mice. Irrespective of the route of immunization, CpG or Poly I:C adjuvanted TMC-PA nanoparticles induced a significantly higher humoral response (total serum IgG and its isotypes viz., IgG1, IgG2a, and IgG2b, compared to their CpG or Poly I:C PA counterparts. This clearly demonstrates the synergistic behavior of CpG and Poly I:C with TMC nanoparticles. The adjuvant potential of TMC nanoparticles could be observed in all the three routes as the TMC-PA nanoparticles by themselves induced IgG titers (1–1.5 × 105 significantly higher than both CpG PA and Poly I:C PA groups (2–8 × 104. The effect of formulations on T-helper (Th cell development was assessed by quantifying the Th1-dependant (TNF-α, IFN-γ, and IL-2, Th2-dependant (IL-4, IL-6, and IL-10, and Th17-type (IL-17A cytokines. Adjuvanation with CpG and Poly I:C, the TMC-PA nanoparticles triggered a Th1 skewed immune response, as suggested by an increase in the levels of total IgG2a along with IFN-γ cytokine production. Interestingly, the TMC-PA group showed a Th2-biased

Gastrointestinal helminths may affect host susceptibility to anthrax through seasonal immune trade-offs.

Science.gov (United States)

Cizauskas, Carrie A; Turner, Wendy C; Wagner, Bettina; Küsters, Martina; Vance, Russell E; Getz, Wayne M

2014-11-12

Most vertebrates experience coinfections, and many pathogen-pathogen interactions occur indirectly through the host immune system. These interactions are particularly strong in mixed micro-macroparasite infections because of immunomodulatory effects of helminth parasites. While these trade-offs have been examined extensively in laboratory animals, few studies have examined them in natural systems. Additionally, many wildlife pathogens fluctuate seasonally, at least partly due to seasonal host immune changes. We therefore examined seasonality of immune resource allocation, pathogen abundance and exposure, and interactions between infections and immunity in plains zebra (Equus quagga) in Etosha National Park (ENP), Namibia, a system with strongly seasonal patterns of gastrointestinal (GI) helminth infection intensity and concurrent anthrax outbreaks. Both pathogens are environmentally transmitted, and helminth seasonality is driven by environmental pressures on free living life stages. The reasons behind anthrax seasonality are currently not understood, though anthrax is less likely directly driven by environmental factors. We measured a complex, interacting set of variables and found evidence that GI helminth infection intensities, eosinophil counts, IgE and IgGb antibody titers, and possibly IL-4 cytokine signaling were increased in wetter seasons, and that ectoparasite infestations and possibly IFN-γ cytokine signaling were increased in drier seasons. Monocyte counts and anti-anthrax antibody titers were negatively associated with wet season eosinophilia, and monocytes were negatively correlated with IgGb and IgE titers. Taken together, this supports the hypothesis that ENP wet seasons are characterized by immune resource allocation toward Th-2 type responses, while Th1-type immunity may prevail in drier seasons, and that hosts may experience Th1-Th2 trade-offs. We found evidence that this Th2-type resource allocation is likely driven by GI parasite infections

Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant

OpenAIRE

Kelly, Cassandra D; O'Loughlin, Chris; Gelder, Frank B; Peterson, Johnny W; Sower, Laurie E; Cirino, Nick M

2007-01-01

Background There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxin...

Rabies virus glycoprotein as a carrier for anthrax protective antigen

International Nuclear Information System (INIS)

Smith, Mary Ellen; Koser, Martin; Xiao Sa; Siler, Catherine; McGettigan, James P.; Calkins, Catherine; Pomerantz, Roger J.; Dietzschold, Bernhard; Schnell, Matthias J.

2006-01-01

Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems

Evaluation of clinical and serological findings for diagnosis of cutaneous anthrax infection after an outbreak.

Science.gov (United States)

Gulseren, Duygu; Süzük-Yıldız, Serap; Çelebi, Bekir; Kılıç, Selçuk

2017-09-01

Anthrax, caused by the bacterium Bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. We aimed to evaluate clinical findings and risk factors of patients with cutaneous anthrax infection and report anti-lethal factor (LF) IgG and anti-protective antigen (PA) IgG titers in the serologic diagnosis of disease. In this study, serum samples of 18 cutaneous anthrax patients were collected and anti-LF IgG and anti-PA IgG titers were measured by enzyme-linked immunosorbent assay (ELISA). Twelve (67%) males and 6 (33%) females, with a mean age of 36.06 ± 16.58 years were included in the study. Risk factors identified in the patient population studied were slaughtering (28%), flaying (56%), chopping meat (67%), burying diseased animal corpses (17%) and milking (6%) livestock. Black eschar formation (94%), pruritus (78%) and painful lymphadenopathy (61%) were first three common clinical signs and symptoms, respectively. Fourteen (78%) patients produced a positive IgG response against PA, 11 (61%) patients produced against LF. Three (17%) patients had no response to either antigen. A detailed history of contact with sick animals or animal products along with clinical findings should be taken at the first step for the diagnosis of cutaneous anthrax infection. Serologic detection of anti-LF IgG and anti-PA IgG with ELISA may be useful auxillary method for establishing the diagnosis.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

Science.gov (United States)

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Food Insecurity in Outbreak of Anthrax Infections among Humans and Hippopotamuses Living in a Game Reserve Area, Rural Zambia.

Science.gov (United States)

Lehman, Mark W; Craig, Allen S; Malama, Constantine; Kapina-Kany'anga, Muzala; Malenga, Philip; Munsaka, Fanny; Muwowo, Sergio; Shadomy, Sean; Marx, Melissa A

2017-09-01

In September 2011, a total of 511 human cases of anthrax (Bacillus anthracis) infection and 5 deaths were reported in a game management area in the district of Chama, Zambia, near where 85 hippopotamuses (Hippopotamus amphibious) had recently died of suspected anthrax. The human infections generally responded to antibiotics. To clarify transmission, we conducted a cross-sectional, interviewer-administered household survey in villages where human anthrax cases and hippopotamuses deaths were reported. Among 284 respondents, 84% ate hippopotamus meat before the outbreak. Eating, carrying, and preparing meat were associated with anthrax infection. Despite the risk, 23% of respondents reported they would eat meat from hippopotamuses found dead again because of food shortage (73%), lack of meat (12%), hunger (7%), and protein shortage (5%). Chronic food insecurity can lead to consumption of unsafe foods, leaving communities susceptible to zoonotic infection. Interagency cooperation is necessary to prevent outbreaks by addressing the root cause of exposure, such as food insecurity.

Recent outbreak of cutaneous anthrax in Bangladesh: clinico-demographic profile and treatment outcome of cases attended at Rajshahi Medical College Hospital

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Siddiqui Muhammad

2012-08-01

Full Text Available Abstract Background Human cutaneous anthrax results from skin exposure to B. anthracis, primarily due to occupational exposure. Bangladesh has experienced a number of outbreaks of cutaneous anthrax in recent years. The last episode occurred from April to August, 2011 and created mass havoc due to its dreadful clinical outcome and socio-cultural consequences. We report here the clinico-demographic profile and treatment outcome of 15 cutaneous anthrax cases attended at the Dermatology Outpatient Department of Rajshahi Medical College Hospital, Bangladesh between April and August, 2011 with an aim to create awareness for early case detection and management. Findings Anthrax was suspected primarily based on cutaneous manifestations of typical non-tender ulcer with black eschar, with or without oedema, and a history of butchering, or dressing/washing of cattle/goat or their meat. Diagnosis was established by demonstration of large gram-positive rods, typically resembling B. anthracis under light microscope where possible and also by ascertaining therapeutic success. The mean age of cases was 21.4 years (ranging from 3 to 46 years, 7 (46.7% being males and 8 (53.3% females. The majority of cases were from lower middle socioeconomic status. Types of exposures included butchering (20%, contact with raw meat (46.7%, and live animals (33.3%. Malignant pustule was present in upper extremity, both extremities, face, and trunk at frequencies of 11 (73.3%, 2 (13.3%, 1 (6.7% and 1 (6.7% respectively. Eight (53.3% patients presented with fever, 7 (46.7% had localized oedema and 5 (33.3% had regional lymphadenopathy. Anthrax was confirmed in 13 (86.7% cases by demonstration of gram-positive rods. All cases were cured with 2 months oral ciprofloxacin combined with flucoxacillin for 2 weeks. Conclusions We present the findings from this series of cases to reinforce the criteria for clinical diagnosis and to urge prompt therapeutic measures to treat

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

National Research Council Canada - National Science Library

Heine, H. S; Bassett, J; Miller, L; Bassett, A; Ivins, B. E; Lehous, D; Arhin, F. F; Parr, Jr., T. R; Moeck, G

2008-01-01

The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days...

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.

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

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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.

[PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].

Science.gov (United States)

Popova, P Yu; Mikshis, N I

2016-01-01

Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering prearations, created based on members of geni of Salmonella, Lactobacillus and adenoviruses.

Estimating the location and spatial extent of a covert anthrax release.

Directory of Open Access Journals (Sweden)

Judith Legrand

2009-01-01

Full Text Available Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. A back-calculation method is developed allowing the characterization of the release based on the data on the first few observed cases of the subsequent outbreak, meteorological data, population densities, and data on population travel patterns. We evaluate this method on small simulated anthrax outbreaks (about 25-35 cases and show that it could date and localize a release after a few cases have been observed, although misspecifications of the spore dispersion model, or the within-host dynamics model, on which the method relies can bias the estimates. Our method could also provide an estimate of the outbreak's geographical extent and, as a consequence, could help to identify populations at risk and, therefore, requiring prophylactic treatment. Our analysis demonstrates that while estimates based on the first ten or 15 observed cases were more accurate and less sensitive to model misspecifications than those based on five cases, overall mortality is minimized by targeting prophylactic treatment early on the basis of estimates made using data on the first five cases. The method we propose could provide early estimates of the time, strength, and location of an aerosolized anthrax release and the geographical extent of the subsequent outbreak. In addition, estimates of release features could be used to parameterize more detailed models allowing the simulation of control strategies and intervention logistics.

[Anthrax meningoencephalitis: a case following a cutaneous lesion in Morocco].

Science.gov (United States)

Ziadi, A; Hachimi, A; Soraa, N; Tassi, N; Nejmi, H; Elkhayari, M; Samkaoui, M A

2014-05-01

Anthrax meningoencephalitis is very rare especially following skin location. We report a case of meningoencephalitis secondary to skin lesion. The diagnosis is based on clinical presentation and confirmed by microbiological tests. Its evolution remains fatal despite aggressive resuscitation. Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

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

Science.gov (United States)

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

2012-11-07

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

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

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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".

A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein.

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Michael S Rogers

Full Text Available Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA, a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2 protein and tumor endothelial marker 8 (TEM8. Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein-protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication.

America’s Food: Does Anthrax Pose A Threat?

Science.gov (United States)

2002-04-01

a 1996 JAMA article, “Unexplained Severe Illness Possibly Associated with Consumption of Kombucha Tea - Iowa 1995.”13 For clarification, the... Kombucha “mush- room” is a “ symbiotic colony of several species of yeast and bacteria that are bound to- gether by a surrounding membrane.”14 Dr. Sadjadi...described an outbreak in Iran of cuta- 9 neous anthrax related to the Kombucha mushroom. In 1996 in a village on the outskirts of Tehran, 20 people

Anthrax in America: A Chronology and Analysis of the Fall 2001 Attacks

Science.gov (United States)

2002-11-01

Glenville, CT, 55 miles west of Oxford. • Officials confirm that the anthrax spores in a letter received by Santiago, Chile pediatrician Antonio Barfi were...process of opening the Leahy letter after two weeks of planning and rehearsals. In charge is John Ezzell , a man described by the Weekend Australian as

The Importance of Health Risk Communication in the Creation of the Anthrax Vaccine Immunization Program

National Research Council Canada - National Science Library

Freeman, Bradley

2001-01-01

... press. This paper suggests that a more proactive educational program with a greater utilization of health risk communication techniques would have reduced much of the negative reaction to the anthrax vaccine...

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.

Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function.

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Jianjun Sun

Full Text Available BACKGROUND: Cell-surface receptors play essential roles in anthrax toxin action by providing the toxin with a high-affinity anchor and self-assembly site on the plasma membrane, mediating the toxin entry into cells through endocytosis, and shifting the pH threshold for prepore-to-pore conversion of anthrax toxin protective antigen (PA to a more acidic pH, thereby inhibiting premature pore formation. Each of the two known anthrax toxin receptors, ANTXR1 and ANTXR2, has an ectodomain comprised of an N-terminal von Willebrand factor A domain (VWA, which binds PA, and an uncharacterized immunoglobulin-like domain (Ig that connects VWA to the membrane-spanning domain. Potential roles of the receptor Ig domain in anthrax toxin action have not been investigated heretofore. METHODOLOGY/PRINCIPAL FINDINGS: We expressed and purified the ANTXR2 ectodomain (R2-VWA-Ig in E. coli and showed that it contains three disulfide bonds: one in R2-VWA and two in R2-Ig. Reduction of the ectodomain inhibited functioning of the pore, as measured by K(+ release from liposomes or Chinese hamster ovary cells or by PA-mediated translocation of a model substrate across the plasma membrane. However, reduction did not affect binding of the ectodomain to PA or the transition of ectodomain-bound PA prepore to the pore conformation. The inhibitory effect depended specifically on reduction of the disulfides within R2-Ig. CONCLUSIONS/SIGNIFICANCE: We conclude that disulfide integrity within R2-Ig is essential for proper functioning of receptor-bound PA pore. This finding provides a novel venue to investigate the mechanism of anthrax toxin action and suggests new strategies for inhibiting toxin action.

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

OpenAIRE

FUE-SANG LIEN; HUA JI; EUGENE YEE; BILL KOURNIKAKIS

2010-01-01

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 ...

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

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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.

Enhancement of an Analytical Method for the Determination of Squalene in Anthrax Vaccine Absorbed Formulations

National Research Council Canada - National Science Library

Spanggord, Ronald J; Sun, Meg; Lim, Peter; Ellis, William Y

2006-01-01

Specific lots of anthrax vaccine adsorbed administered to members of the U.S. Armed Forces have been alleged to contain squalene, a chemical purported to be associated with illnesses of Gulf War veterans...

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

NARCIS (Netherlands)

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

2005-01-01

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

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

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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.

Antibodies to Anthrax Toxin in Humans and Guinea Pigs and Their Relevance to Protective Immunity

National Research Council Canada - National Science Library

Turnbull, P

1988-01-01

... stimulation of more than just production of antibody to PA. Titers to the three components in sera of individuals with histories of clinically diagnosed anthrax as well as from human vaccinees are included in the report.

Prevention, detection, and response to anthrax outbreak in Northern Tanzania using one health approach: A case study of Selela ward in Monduli district

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Elibariki R. Mwakapeje

2017-11-01

Full Text Available Background: Anthrax is an infectious fatal zoonotic disease caused by Bacillus anthracis. Anthrax outbreak was confirmed in samples of wild animals following rumors of the outbreak in wild animals, livestock, and humans in Selela ward, Monduli district of Northern Tanzania. Therefore, a multi-sectorial team was deployed for outbreak response in the affected areas. Objectives: The aim of the response was to manage the outbreak in a One Health approach and specifically: (i To determine the magnitude of anthrax outbreak in humans, livestock, and wild animals in Selela ward, (ii to assess the outbreak local response capacity, (iii to establish mechanisms for safe disposal of animal carcasses in the affected areas, and (iv to mount effective control and preventive strategies using One Health approach in the affected areas. Materials and Methods: This was a cross-sectional field survey using: (i Active searching of suspected human cases at health facilities and community level, (ii physical counting and disposal of wild animal carcasses in the affected area, (iii collection of specimens from suspected human cases and animal carcasses for laboratory analysis, and (iv meetings with local animal and human health staff, political, and traditional leaders at local levels. We analyzed data by STATA software, and a map was created using Quantum GIS software. Results: A total of 21 humans were suspected, and most of them (62% being from Selela ward. The outbreak caused deaths of 10 cattle, 26 goats, and three sheep, and 131 wild animal carcasses were discarded the majority of them being wildebeest (83%. Based on laboratory results, three blood smears tested positive for anthrax using Giemsa staining while two wildebeest samples tested positive and five human blood samples tested negative for anthrax using quantitative polymerase chain reaction techniques. Clinical forms of anthrax were also observed in humans and livestock which suggest that wild animals may

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

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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.

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.

Anthrax outbreak in a Swedish beef cattle herd - 1st case in 27 years: Case report

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Granberg Malin

2010-02-01

Full Text Available Abstract After 27 years with no detected cases, an outbreak of anthrax occurred in a beef cattle herd in the south of Sweden. The outbreak was unusual as it occurred in winter, in animals not exposed to meat-and-bone meal, in a non-endemic country. The affected herd consisted of 90 animals, including calves and young stock. The animals were kept in a barn on deep straw bedding and fed only roughage. Seven animals died during 10 days, with no typical previous clinical signs except fever. The carcasses were reportedly normal in appearance, particularly as regards rigor mortis, bleeding and coagulation of the blood. Subsequently, three more animals died and anthrax was suspected at necropsy and confirmed by culture and PCR on blood samples. The isolated strain was susceptible to tetracycline, ciprofloxacin and ampicillin. Subtyping by MLVA showed the strain to cluster with isolates in the A lineage of Bacillus anthracis. Environmental samples from the holding were all negative except for two soil samples taken from a spot where infected carcasses had been kept until they were picked up for transport. The most likely source of the infection was concluded to be contaminated roughage, although this could not be substantiated by laboratory analysis. The suspected feed was mixed with soil and dust and originated from fields where flooding occurred the previous year, followed by a dry summer with a very low water level in the river allowing for the harvesting on soil usually not exposed. In the early 1900s, animal carcasses are said to have been dumped in this river during anthrax outbreaks and it is most likely that some anthrax spores could remain in the area. The case indicates that untypical cases in non-endemic areas may be missed to a larger extent than previously thought. Field tests allowing a preliminary risk assessment of animal carcasses would be helpful for increased sensitivity of detection and prevention of further exposure to the causative

The use of anthrax and orthopox therapeutic antibodies from human origin in biodefense

International Nuclear Information System (INIS)

Stienstra, S.

2009-01-01

It is impossible to protect whole nations from the effects of bioterrorism by preventive vaccination; there are too many possible agents, costs would be exorbitantly high, and the health risks associated with complex mass vaccination programs would be unacceptable. Adequate protection, however, could be provided via a combination of rapid detection and diagnosis and the treatment of those exposed with drugs which would be beneficial in all stages of disease. Monoclonal antibodies, preferably from human origin to prevent severe complications, which neutralize or block the pathological effects of biological agents, are the optimal candidates to be deployed in case of biological warfare or a bioterrorist event. The human body is one of the better and most suitably equipped places for the generation of monoclonal antibodies which are to be used effectively in humans for treatment. Such antibodies will be of optimal physiological specificity, affinity, and pharmacological properties. In addition, the chances on severe adverse effects and cross-reactivity with human tissues will be slim. Therefore the human immune response is used by the Dutch company IQ Therapeutics, a spin-off of the Groningen University, as a basis for selecting the antibodies. People, immunised against or infected with the agent in question, donate blood cells voluntarily, which are used to generate fully human monoclonal antibodies. In this way effective therapeutics against the protective antigen (PA) and lethal factor (LF) toxin components of Bacillus anthracis are developed and currently antibodies against orthopox viruses are generated as well from donors, which have been immunized with vaccinia. Other projects are the development of therapeutic antibodies for MRSA (antibiotics resistant Staphylococcus aureus) and Enterococcus spp. Both human antibodies against the anthrax toxin components are efficacious in vitro and in pre- and post-exposure settings in mice and rabbits. The anti-LF antibody

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

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Jie Wang

2009-07-01

Full Text Available 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.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.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.

One-pot synthesis of strongly fluorescent DNA-CuInS2 quantum dots for label-free and ultrasensitive detection of anthrax lethal factor DNA

International Nuclear Information System (INIS)

Liu, Ziping; Su, Xingguang

2016-01-01

Herein, high quality DNA-CuInS 2 QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS 2 QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS 2 QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition. The as-prepared DNA-CuInS 2 QDs have high stability, good water-solubility and low toxicity. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I 0 (I 0 is the original fluorescence intensity of DNA-CuInS 2 QDs, and I is the fluorescence intensity of DNA-CuInS 2 QDs/GO with the addition of various concentrations of anthrax lethal factor DNA) and the concentration of anthrax lethal factor DNA in the range of 0.029–0.733 nmol L −1 with a detection limit of 0.013 nmol L −1 . The proposed method has been successfully applied to the determination of anthrax lethal factor DNA sequence in human serum samples with satisfactory results. Because of low toxicity and fine biocompatibility, DNA-CuInS 2 QDs also hold potential applications in bioimaging. - Highlights: • Strongly fluorescent DNA-QDs were successfully prepared by a one-pot hydrothermal method with quantum yield up to 23.4%. • A biosensor for label-free detection of anthrax lethal factor DNA was established based on the as-prepared DNA-QDs. • The DNA sensor took advantage of the feature that ssDNA binds to GO with significantly higher affinity than dsDNA. • Good sensitivity and selectivity were obtained. • This method was utilized to detect

Indirect Detection Of Bacillus Anthracis (Anthrax) Using Amplified Gamma Phage-Based Assays

Science.gov (United States)

2007-11-01

enter 26 Figure 3.0 Model of anthrax toxin entry into eukaryotic cells 27 the lungs and into the mucus membrane...extract from porcine and mixture meat and milk peptones, 2.0 g D(+) glucose, 5.0 g NaCl and 2.5 g disodium phosphate) and TSB (g/L: 17.0 pancreatic...are present in blood serum, lymph fluid, gastric secretions, milk , and saliva. Serum antibody concentrations are commonly determined using the

Role of the Antigen Capture Pathway in the Induction of a Neutralizing Antibody Response to Anthrax Protective Antigen

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Anita Verma

2018-02-01

Full Text Available Toxin neutralizing antibodies represent the major mode of protective immunity against a number of toxin-mediated bacterial diseases, including anthrax; however, the cellular mechanisms that lead to optimal neutralizing antibody responses remain ill defined. Here we show that the cellular binding pathway of anthrax protective antigen (PA, the binding component of anthrax toxin, determines the toxin neutralizing antibody response to this antigen. PA, which binds cellular receptors and efficiently enters antigen-presenting cells by receptor-mediated endocytosis, was found to elicit robust anti-PA IgG and toxin neutralizing antibody responses. In contrast, a receptor binding-deficient mutant of PA, which does not bind receptors and only inefficiently enters antigen-presenting cells by macropinocytosis, elicited very poor antibody responses. A chimeric protein consisting of the receptor binding-deficient PA mutant tethered to the binding subunit of cholera toxin, which efficiently enters cells using the cholera toxin receptor rather than the PA receptor, elicited an anti-PA IgG antibody response similar to that elicited by wild-type PA; however, the chimeric protein elicited a poor toxin neutralizing antibody response. Taken together, our results demonstrate that the antigen capture pathway can dictate the magnitudes of the total IgG and toxin neutralizing antibody responses to PA as well as the ratio of the two responses.

Forecasting of interaction between bee propolis and protective antigenic domain in anthrax using the software and bioinformatics web servers

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Elmira Mohammadi

2017-01-01

Full Text Available Background: Protective antigen of anthrax toxin, after touching the cell receptors, plays an important role in the pathogenesis of toxin. The purpose of this study was to investigate the interaction of anthrax toxin protective antigen and four great combination propolis included caffeic acid, benzyl caffeate, cinnamic acid and kaempferol using the softwares and bioinformatics web servers. Methods: Three-dimensional structure of protective antigen (receptor obtains from Protein Data Bank (PDB. Four of the main components from propolis were selected          as ligand and their 3D-structures were obtained from ChemSpider and ZINC     compound database. The interaction of each ligand and receptor was assessed                   by SwissDock server (http://www.swissdock.ch/ and BSP-SLIM server (http://zhanglab.ccmb.med.umich.edu/BSP-SLIM. Docking results appears with Fullfitness numbers (in kcal/mol. Identification of amino acids involved in ligand and receptor interaction, was performed using the Chimera software; UCSF Chimera program (http://www.cgl.ucsf.edu/. Results: The results of interaction between propolis components and protective antigen by BSP-SLIM server showed that the most interaction was related with benzyl caffeate, caffeic acid, kaempferol and cinnamic acid, respectively. Results for the desired ligand Interaction with protective antigen genes using SwissDock server showed that the caffeic acid had ΔG equals -9.10 kcal/mol and FullFitness equal to -993.16 kcal/mol respectively. The analysis of interaction between ligands with amino-acids of protective antigen indicated that the interaction of Caffeic acid whit Glutamic acid 117 had energy -15.5429 kcal/mol. Conclusion: Finding strong and safe inhibitors for anthrax toxin is very useful method for inhibiting its toxicity to cell. In this study the binding ability of four flavonoids to protective antigen was studied. Glutamic acid 117 is very effective

Immunoassay for Capsular Antigen of Bacillus anthracis Enables Rapid Diagnosis in a Rabbit Model of Inhalational Anthrax.

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Marcellene A Gates-Hollingsworth

Full Text Available Inhalational anthrax is a serious biothreat. Effective antibiotic treatment of inhalational anthrax requires early diagnosis; the further the disease has progressed, the less the likelihood for cure. Current means for diagnosis such as blood culture require several days to a result and require advanced laboratory infrastructure. An alternative approach to diagnosis is detection of a Bacillus anthracis antigen that is shed into blood and can be detected by rapid immunoassay. The goal of the study was to evaluate detection of poly-γ-D-glutamic acid (PGA, the capsular antigen of B. anthracis, as a biomarker surrogate for blood culture in a rabbit model of inhalational anthrax. The mean time to a positive blood culture was 26 ± 5.7 h (mean ± standard deviation, whereas the mean time to a positive ELISA was 22 ± 4.2 h; P = 0.005 in comparison with blood culture. A lateral flow immunoassay was constructed for detection of PGA in plasma at concentrations of less than 1 ng PGA/ml. Use of the lateral flow immunoassay for detection of PGA in the rabbit model found that antigen was detected somewhat earlier than the earliest time point at which the blood culture became positive. The low cost, ease of use, and rapid time to result of the lateral flow immunoassay format make an immunoassay for PGA a viable surrogate for blood culture for detection of infection in individuals who have a likelihood of exposure to B. anthracis.

One-pot synthesis of strongly fluorescent DNA-CuInS{sub 2} quantum dots for label-free and ultrasensitive detection of anthrax lethal factor DNA

Energy Technology Data Exchange (ETDEWEB)

Liu, Ziping; Su, Xingguang, E-mail: suxg@jlu.edu.cn

2016-10-26

Herein, high quality DNA-CuInS{sub 2} QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS{sub 2} QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS{sub 2} QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition. The as-prepared DNA-CuInS{sub 2} QDs have high stability, good water-solubility and low toxicity. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I{sub 0} (I{sub 0} is the original fluorescence intensity of DNA-CuInS{sub 2} QDs, and I is the fluorescence intensity of DNA-CuInS{sub 2} QDs/GO with the addition of various concentrations of anthrax lethal factor DNA) and the concentration of anthrax lethal factor DNA in the range of 0.029–0.733 nmol L{sup −1} with a detection limit of 0.013 nmol L{sup −1}. The proposed method has been successfully applied to the determination of anthrax lethal factor DNA sequence in human serum samples with satisfactory results. Because of low toxicity and fine biocompatibility, DNA-CuInS{sub 2} QDs also hold potential applications in bioimaging. - Highlights: • Strongly fluorescent DNA-QDs were successfully prepared by a one-pot hydrothermal method with quantum yield up to 23.4%. • A biosensor for label-free detection of anthrax lethal factor DNA was established based on the as-prepared DNA-QDs. • The DNA sensor took advantage of the feature that ssDNA binds to GO with significantly higher affinity than dsDNA. • Good sensitivity and selectivity were

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

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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.

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

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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

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

National Research Council Canada - National Science Library

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

2008-01-01

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

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

Science.gov (United States)

2010-01-01

... have handled anthrax material is thorough cleansing of the hands and arms with liquid soap and running... Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND... request to the Scientific Services, Meat and Poultry Inspection, Food Safety and Inspection Service, U.S...

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?

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

Science.gov (United States)

2010-01-01

...; cleaning and disinfection of infected livestock pens and driveways. 309.7 Section 309.7 Animals and Animal... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and... followed immediately by a thorough disinfection of the exposed premises by soaking the ground, fences...

Anthrax Cases Associated with Animal-Hair Shaving Brushes.

Science.gov (United States)

Szablewski, Christine M; Hendricks, Kate; Bower, William A; Shadomy, Sean V; Hupert, Nathaniel

2017-05-01

During the First World War, anthrax cases in the United States and England increased greatly and seemed to be associated with use of new shaving brushes. Further investigation revealed that the source material and origin of shaving brushes had changed during the war. Cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. Unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data, and case reports indicated that these cases originated from the use of ineffectively disinfected animal-hair shaving brushes. This historical information is relevant to current public health practice because renewed interest in vintage and animal-hair shaving brushes has been seen in popular culture. This information should help healthcare providers and public health officials answer questions on this topic.

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

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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.

Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.

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Chen Sun

Full Text Available A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs. Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.

Temporal dynamics in microbial soil communities at anthrax carcass sites.

Science.gov (United States)

Valseth, Karoline; Nesbø, Camilla L; Easterday, W Ryan; Turner, Wendy C; Olsen, Jaran S; Stenseth, Nils Chr; Haverkamp, Thomas H A

2017-09-26

Anthrax is a globally distributed disease affecting primarily herbivorous mammals. It is caused by the soil-dwelling and spore-forming bacterium Bacillus anthracis. The dormant B. anthracis spores become vegetative after ingestion by grazing mammals. After killing the host, B. anthracis cells return to the soil where they sporulate, completing the lifecycle of the bacterium. Here we present the first study describing temporal microbial soil community changes in Etosha National Park, Namibia, after decomposition of two plains zebra (Equus quagga) anthrax carcasses. To circumvent state-associated-challenges (i.e. vegetative cells/spores) we monitored B. anthracis throughout the period using cultivation, qPCR and shotgun metagenomic sequencing. The combined results suggest that abundance estimation of spore-forming bacteria in their natural habitat by DNA-based approaches alone is insufficient due to poor recovery of DNA from spores. However, our combined approached allowed us to follow B. anthracis population dynamics (vegetative cells and spores) in the soil, along with closely related organisms from the B. cereus group, despite their high sequence similarity. Vegetative B. anthracis abundance peaked early in the time-series and then dropped when cells either sporulated or died. The time-series revealed that after carcass deposition, the typical semi-arid soil community (e.g. Frankiales and Rhizobiales species) becomes temporarily dominated by the orders Bacillales and Pseudomonadales, known to contain plant growth-promoting species. Our work indicates that complementing DNA based approaches with cultivation may give a more complete picture of the ecology of spore forming pathogens. Furthermore, the results suggests that the increased vegetation biomass production found at carcass sites is due to both added nutrients and the proliferation of microbial taxa that can be beneficial for plant growth. Thus, future B. anthracis transmission events at carcass sites may be

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

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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.

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

Science.gov (United States)

Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

2013-02-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

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

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T. Scott Devera

2015-06-01

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

Anthrax toxin: the long and winding road that leads to the kill.

Science.gov (United States)

Abrami, Laurence; Reig, Nuria; van der Goot, F Gisou

2005-02-01

The past five years have led to a tremendous increase in our molecular understanding of the mode of action of the anthrax toxin, one of the two main virulence factors produced by Bacillus anthracis. The structures of each of the three components of the toxin--lethal factor (LF), edema factor (EF) and protective antigen (PA)--have been solved not only in their monomeric forms but, depending on the subunit, in a heptameric form, bound to their substrate, co-factor or receptor. The endocytic route followed by the toxin has also been unraveled and the enzymatic mechanisms of EF and LF elucidated.

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

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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.

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

Science.gov (United States)

Kutyrev, V V; Smirnova, N I

2003-01-01

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

Transient Co-Expression of Post-Transcriptional Gene Silencing Suppressors for Increased in Planta Expression of a Recombinant Anthrax Receptor Fusion Protein

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Kittipong Rattanaporn

2011-08-01

Full Text Available Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin, CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA domain of human capillary morphogenesis 2 (CMG2, an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG. We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS: p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI, with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

Transient co-expression of post-transcriptional gene silencing suppressors for increased in planta expression of a recombinant anthrax receptor fusion protein.

Science.gov (United States)

Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M; McDonald, Karen A

2011-01-01

Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI.

Inhalation Anthrax (Ames aerosol) in Naive and Vaccinated New Zealand Rabbits: Characterizing the Spread of Bacteria from Lung Deposition to Bacteremia

Science.gov (United States)

2012-06-28

Lond.) 51, 372–385. Henderson, D. W., Peacock , S., and Belton, F. C. (1956). Observations on the prophylaxis of experimental pulmonary anthrax in...terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums

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

Science.gov (United States)

Brown, Bruce K; Cox, Josephine; Gillis, Anita; VanCott, Thomas C; Marovich, Mary; Milazzo, Mark; Antonille, Tanya Santelli; Wieczorek, Lindsay; McKee, Kelly T; Metcalfe, Karen; Mallory, Raburn M; Birx, Deborah; Polonis, Victoria R; Robb, Merlin L

2010-11-05

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). 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. The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. ClinicalTrials.gov NCT00057525.

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

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Kym S Antonation

2016-09-01

Full Text Available 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.

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.

A Retrospective Study on the Epidemiology of Anthrax, Foot and Mouth Disease, Haemorrhagic Septicaemia, Peste des Petits Ruminants and Rabies in Bangladesh, 2010-2012

Science.gov (United States)

Mondal, Shankar P.; Yamage, Mat

2014-01-01

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 (pBangladesh. PMID:25101836

Dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor.

Science.gov (United States)

Wang, Qi-Xian; Xue, Shi-Fan; Chen, Zi-Han; Ma, Shi-Hui; Zhang, Shengqiang; Shi, Guoyue; Zhang, Min

2017-08-15

In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO 2 -Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO 2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO 2 -Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The Effects of Anthrax Lethal Toxin on Host Barrier Function

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David M. Frucht

2011-06-01

Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

Perturbing Tandem Energy Transfer in Luminescent Heterobinuclear Lanthanide Coordination Polymer Nanoparticles Enables Real-Time Monitoring of Release of the Anthrax Biomarker from Bacterial Spores.

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Gao, Nan; Zhang, Yunfang; Huang, Pengcheng; Xiang, Zhehao; Wu, Fang-Ying; Mao, Lanqun

2018-06-05

Lanthanide-based luminescent sensors have been widely used for the detection of the anthrax biomarker dipicolinic acid (DPA). However, mainly based on DPA sensitization to the lanthanide core, most of them failed to realize robust detection of DPA in bacterial spores. We proposed a new strategy for reliable detection of DPA by perturbing a tandem energy transfer in heterobinuclear lanthanide coordination polymer nanoparticles simply constructed by two kinds of lanthanide ions, Tb 3+ and Eu 3+ , and guanosine 5'-monophosphate. This smart luminescent probe was demonstrated to exhibit highly sensitive and selective visual luminescence color change upon exposure to DPA, enabling accurate detection of DPA in complex biosystems such as bacterial spores. DPA release from bacterial spores on physiological germination was also successfully monitored in real time by confocal imaging. This probe is thus expected to be a powerful tool for efficient detection of bacterial spores in responding to anthrax threats.

Monitoring the kinetics of the pH-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.

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Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; McGinn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E P; Pentelute, B L; Collier, R John; Fisher, Mark T

2013-09-17

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å β barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor, from the endosome to the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance and biolayer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from 7.5 to 5.0, mirroring acidification of the endosome. Once it had undergone the transition, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto electron microscopy grids, where PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early (pH 5.5) or late (pH 5.0) endosomal pH conditions. Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and the soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions.

Monitoring the kinetics of the pH driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance

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Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; Mcginn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E. P.; Pentelute, B. L.; Collier, R. John; Fisher, Mark T.

2013-01-01

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å beta barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor (EF), from the endosome into the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance (SPR) and bio-layer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from pH 7.5 to pH 5.0, mirroring acidification of the endosome. Once transitioned, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto EM grids, where the PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early or late endosomal pH conditions (5.5 to 5.0 respectively). Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions. PMID:23964683

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

OpenAIRE

Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

2012-01-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6,...

Rapid assessment of agents of biological terrorism: defining the differential diagnosis of inhalational anthrax using electronic communication in a practice-based research network.

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Temte, Jonathan L; Anderson, Anna Lisa

2004-01-01

Early detection of bioterrorism requires assessment of diagnoses assigned to cases of rare diseases with which clinicians have little experience. In this study, we evaluated the process of defining the differential diagnosis for inhalational anthrax using electronic communication within a practice-based research network (PBRN) and compared the results with those obtained from a nationwide random sample of family physicians with a mailed instrument. We distributed survey instruments by e-mail to 55 physician members of the Wisconsin Research Network (WReN), a regional PBRN. The instruments consisted of 3 case vignettes randomly drawn from a set describing 11 patients with inhalational anthrax, 2 with influenza A, and 1 with Legionella pneumonia. Physicians provided their most likely nonanthrax diagnosis, along with their responses to 4 yes-or-no management questions for each case. Physicians who had not responded at 1 week received a second e-mail with the survey instrument. The comparison group consisted of the nationwide sample of physicians who completed mailed survey instruments. Primary outcome measures were response rate, median response time, and frequencies of diagnostic categories assigned to cases of inhalational anthrax. The PBRN response rate compared favorably with that of the national sample (47.3% vs 37.0%; P = not significant). The median response time for the PBRN was significantly shorter than that for the national sample (2 vs 28 days; P < .001). No significant differences were found between the PBRN and the Midwest subset of the national sample in the frequencies of major diagnostic categories or in case management. Electronic means of creating differential diagnoses for rare infectious diseases of national significance is feasible within PBRNs. Information is much more rapidly acquired and is consistent with that obtained by conventional methods.

Sverdlovsk Anthrax Outbreak: An Educational Case Study

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Steele, S. J.; van der Vink, G.

2002-05-01

In April and May of 1979 an Anthrax epidemic broke out in the city of Sverdlovsk (now Ekaterinburg) in the former Soviet Union. Sixty-four people were reported to have died from the outbreak, although there is still debate concerning the actual number of victims. While Soviet officials initially attributed this outbreak to contaminated meat, the US Government maintained that the outbreak was due to a leakage from a biological weapons facility. We have created and implemented an undergraduate educational exercise based on the forensic analysis of this event. Students were provided case data of the victims, area satellite images and meteorological data. One goal of the exercise was for students to reconstruct the most probable scenario of events through valid inference based on the limited information and uncertainties associated with the data set. Another goal was to make students sensitive to issues of biological weapons and bioterrorism. The exercise was highly rated by students even before the events of September 11. There is a clear need to educate students, particularly in the sciences, to be aware of the signatures of terrorist activities. Evidence of terrorist activities is more likely to appear from unintended discoveries than from active intelligence gathering. We believe our national security can be enhanced by sensitizing those that monitor the natural environment to the signatures of terrorist activities through the types of educational exercises that we have developed.

Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2-Fluorohistidine Labeled Analogue

OpenAIRE

Hu, Lei; Joshi, Sangeeta B.; Andra, Kiran K.; Thakkar, Santosh V.; Volkin, David B.; Bann, James G.; Middaugh, C. Russell

2012-01-01

Protective antigen (PA) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. An analogue of recombinant PA (2-FHis rPA) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. This rPA analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-FHis)....

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

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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.

Uso de la vacuna contra el carbunco en los Estados Unidos de América Use of anthrax vaccine in the United States of America: recommendations of the Advisory Committee on Immunization Practices

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2001-07-01

Full Text Available This piece presents the recommendations of the Advisory Committee on Immunization Practices of the United States of America concerning the use of aluminum hydroxide adsorbed cell-free anthrax vaccine (Anthrax Vaccine Adsorbed, or AVA and the use of chemoprophylaxis against Bacillus anthracis in the United States. The recommended vaccination schedule consists of three subcutaneous injections, at 0, 2, and 4 weeks, and three booster vaccinations, at 6, 12, and 18 months. To maintain immunity, an annual booster injection is recommended. Approximately 95% of vaccinees seroconvert, with a fourfold rise in anti-PA (protective antigen IgG titers after three doses. Analysis of data from the United States' Vaccine Adverse Event Reporting System has documented no pattern of serious adverse events clearly associated with the vaccine, except injection-site reactions. Vaccination is contraindicated in the case of a previous history of anthrax infection or anaphylactic reaction following a previous dose of AVA or any of the vaccine components. In addition, vaccination should be postponed in the case of moderate or severe acute illness. Pregnant women should be vaccinated against anthrax only if the potential benefits of vaccination outweigh the potential risks to the fetus. Vaccination during breast-feeding is not medically contraindicated. Routine preexposure vaccination with AVA is indicated for persons engaged in: a work involving production quantities or concentrations of B. anthracis cultures or b activities with a high potential for aerosol production. For the military and other select populations or for groups for which a calculable risk can be assessed, preexposure vaccination may be indicated. Following confirmed or suspected exposure to B. anthracis, postexposure antibiotic prophylaxis should be administered with ciprofloxacin, ofloxacin, doxycycline, penicillin VK, or amoxicillin. If the vaccine is available, prophylaxis should continue for 4 weeks

Impact of Dendrimer Terminal Group Chemistry on Blockage of the Anthrax Toxin Channel: A Single Molecule Study.

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Yamini, Goli; Kalu, Nnanya; Nestorovich, Ekaterina M

2016-11-15

Nearly all the cationic molecules tested so far have been shown to reversibly block K⁺ current through the cation-selective PA 63 channels of anthrax toxin in a wide nM-mM range of effective concentrations. A significant increase in channel-blocking activity of the cationic compounds was achieved when multiple copies of positively charged ligands were covalently linked to multivalent scaffolds, such as cyclodextrins and dendrimers. Even though multivalent binding can be strong when the individual bonds are relatively weak, for drug discovery purposes we often strive to design multivalent compounds with high individual functional group affinity toward the respective binding site on a multivalent target. Keeping this requirement in mind, here we perform a single-channel/single-molecule study to investigate kinetic parameters of anthrax toxin PA 63 channel blockage by second-generation (G2) poly(amido amine) (PAMAM) dendrimers functionalized with different surface ligands, including G2-NH₂, G2-OH, G2-succinamate, and G2-COONa. We found that the previously reported difference in IC 50 values of the G2-OH/PA 63 and G2-NH₂/PA 63 binding was determined by both on- and off-rates of the reversible dendrimer/channel binding reaction. In 1 M KCl, we observed a decrease of about three folds in k o n and a decrease of only about ten times in t r e s with G2-OH compared to G2-NH₂. At the same time for both blockers, k o n and t r e s increased dramatically with transmembrane voltage increase. PAMAM dendrimers functionalized with negatively charged succinamate, but not carboxyl surface groups, still had some residual activity in inhibiting the anthrax toxin channels. At 100 mV, the on-rate of the G2-succinamate binding was comparable with that of G2-OH but showed weaker voltage dependence when compared to G2-OH and G2-NH₂. The residence time of G2-succinamate in the channel exhibited opposite voltage dependence compared to G2-OH and G2-NH₂, increasing with the cis

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

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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

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

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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

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

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Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

2016-01-01

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

Design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.

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Patke, Sanket; Boggara, Mohan; Maheshwari, Ronak; Srivastava, Sunit K; Arha, Manish; Douaisi, Marc; Martin, Jacob T; Harvey, Ian B; Brier, Matthew; Rosen, Tania; Mogridge, Jeremy; Kane, Ravi S

2014-07-28

The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers. By tuning the valency and linker length, we designed polyvalent inhibitors that were over four orders of magnitude more potent than the corresponding monovalent ligands. This strategy for the rational design of monodisperse polyvalent molecules may not only be broadly applicable for the inhibition of toxins and pathogens, but also for controlling the nanoscale organization of cellular receptors to regulate signaling and the fate of stem cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The medicinal chemistry of botulinum, ricin and anthrax toxins.

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Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

2005-01-01

The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

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

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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. © 2014 Society for Risk Analysis.

Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity

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Lu, Yichen; Friedman, Rachel; Kushner, Nicholas; Doling, Amy; Thomas, Lawrence; Touzjian, Neal; Starnbach, Michael; Lieberman, Judy

2000-07-01

Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, recombinant constructs encoding several HIV antigens up to 500 amino acids were produced. These candidate HIV vaccines are safe in animals and induce CD8 T cells in mice. Constructs encoding gag p24 and nef stimulate gag-specific CD4 proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected donor peripheral blood mononuclear cells in vitro. These results lay the foundation for future clinical vaccine studies.

[Efficacy of enterocin S760 in treatment of mice with anthrax infection due to Bacillus anthracis M-71].

Science.gov (United States)

Svetoch, E A; Borzilov, A I; Eruslanov, B V; Korobova, O V; Kombarova, T I; Levchuk, V P; Teĭmurazov, M G; Stepanshin, Iu G; Marinin, L I; Diatlov, I A

2011-01-01

The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.

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.

Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

Science.gov (United States)

Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

2011-06-01

Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

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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.

Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

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Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.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. PMID:26895308

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

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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.

Pharmacophore selection and redesign of non-nucleotide inhibitors of anthrax edema factor.

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Schein, Catherine H; Chen, Deliang; Ma, Lili; Kanalas, John J; Gao, Jian; Jimenez, Maria Estrella; Sower, Laurie E; Walter, Mary A; Gilbertson, Scott R; Peterson, Johnny W

2012-11-08

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.

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

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Raymond Schuch

2009-08-01

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.

Fatal attraction: vegetation responses to nutrient inputs attract herbivores to infectious anthrax carcass sites.

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Turner, Wendy C; Kausrud, Kyrre L; Krishnappa, Yathin S; Cromsigt, Joris P G M; Ganz, Holly H; Mapaure, Isaac; Cloete, Claudine C; Havarua, Zepee; Küsters, Martina; Getz, Wayne M; Stenseth, Nils Chr

2014-11-22

Parasites can shape the foraging behaviour of their hosts through cues indicating risk of infection. When cues for risk co-occur with desired traits such as forage quality, individuals face a trade-off between nutrient acquisition and parasite exposure. We evaluated how this trade-off may influence disease transmission in a 3-year experimental study of anthrax in a guild of mammalian herbivores in Etosha National Park, Namibia. At plains zebra (Equus quagga) carcass sites we assessed (i) carcass nutrient effects on soils and grasses, (ii) concentrations of Bacillus anthracis (BA) on grasses and in soils, and (iii) herbivore grazing behaviour, compared with control sites, using motion-sensing camera traps. We found that carcass-mediated nutrient pulses improved soil and vegetation, and that BA is found on grasses up to 2 years after death. Host foraging responses to carcass sites shifted from avoidance to attraction, and ultimately to no preference, with the strength and duration of these behavioural responses varying among herbivore species. Our results demonstrate that animal carcasses alter the environment and attract grazing hosts to parasite aggregations. This attraction may enhance transmission rates, suggesting that hosts are limited in their ability to trade off nutrient intake with parasite avoidance when relying on indirect cues. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

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

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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.

Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase.

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Colby, Jennifer M; Krantz, Bryan A

2015-11-06

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.

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Besschetnova, Tatiana Y; Ichimura, Takaharu; Katebi, Negin; St Croix, Brad; Bonventre, Joseph V; Olsen, Bjorn R

2015-03-01

It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

PERILAKU MASYARAKAT DAN FAKTOR LINGKUNGAN YANG BERHUBUNGAN DENGAN KEJADIAN ANTRAKS DI KECAMATAN KODI KABUPATEN SUMBA BARAT DAYA

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Ruben Wadu Willa

2012-09-01

Full Text Available Anthrax is a disease Zoonotic diseases caused by Baccilus anthrakcis. In 2007, there Extraordinary incident (KLB anthrax in District Kodi West Sumba, with 18 people the number of cases and 5 fatalities. This study sursey research in areas that have experienced anthrax incident. Population and sample are heads of households and the environment in the region anthrax incident. The data collected is the data environment consisting of soil pH, organic matter content, and air temperature as well as knowledge, attitude and practice of community. Presentation of data was descriptive. The results showed that the environment consisting of soil pH, organic matter content and air temperature has the potential for survival of baccillus antrakcis, respondents' knowledge about anthrax, anthrax prevention and control is still low. Respondents generally have a pretty good attitude in the response to anthrax, but still there is the behavior of respondents who are at risk for contracting anthrax, such as custom cutting   and   eating   meat   of  dead   animals   and   dispose   of  dead livestockForestry.   Key words: Behavioral and local environment anthrax

Making Communication Strategy Choices in a Fast Evolving Crisis Situation—Results from a Table-Top Discussion on an Anthrax Scenario

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Aino Ruggiero

2016-05-01

Full Text Available This paper aims at clarifying a timely topic of how communication strategy choices are made in evolving, complex crises, such as those caused by terrorism involving chemical, biological, radiological, or nuclear (CBRN agents. This is done by examining data gathered from a table-top discussion among crisis communication experts, focusing on a scenario of an anthrax attack and analysed qualitatively. The communication experts followed the evolving crisis situation by gathering inputs from various actors in the crisis management network, thereby creating situational understanding, and interpreted these inputs for decision-making on communication strategies. The underlying process of coping with complexity in evolving CBRN terrorism crises can be described as a continuous, dynamic process that can best be explained with a combination of traditional and more modern crisis communication approaches. Strategy-making in crisis situations by communication experts is still largely a black box. In this study, a novel approach of decomposing strategy-making by observing a table-top discussion is chosen to clarify the process. By identifying the core elements involved, a more detailed picture of communication strategy-making is created, thus promoting preparedness and professional resilience in the field.

A comparison of the immune response between early exposed and 1 year post exposure to Bacillus anthracis in Indonesia

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Redhono, D.; Kusumawardani, A.; Dirgahayu, P.

2018-03-01

Anthrax is one of the zoonotic diseases that usually affects animals and can be transmitted to humans. Immune response of the body during an infection is the presence of antibodies as an effort to defend the body and it will survive for some time in the blood. The aim study is to find out how the initial response to the formation of antibodies and how these antibodies survive after one year. This study is cohort to people exposed to anthrax and found 130 people exposed to anthrax. The most risk factor was direct contact and consumed infected animal meat, which was 34.6%. Clinical manifestations of the skin were 12.3% and all respondents showed positive IgG. While 87.7% did not show any anthrax symptoms. IgG serum examination after 1 year of exposure to anthrax obtained 3.8% still detected antibodies in the body. The relationship between IgG titers with clinical manifestations of anthrax at one year post-outbreak is highly significant p 0.028. In conclusion a significant association between the clinical manifestation with antibody serum anthrax and it still detected after one-year post outbreaks of anthrax.

Afican Health Sciences Vol 10 No 2.pmd

African Journals Online (AJOL)

Administrator

2007-01-23

Jan 23, 2007 ... Key Words: Zimbabwe, Gokwe, Outbreak, Anthrax, Bacillus anthracis. African Health Sciences 2010; 10(2): 159 - 164. Introduction. Anthrax is ... and establish factors associated with contracting anthrax in the affected area.

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

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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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

International Nuclear Information System (INIS)

Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

2008-01-01

Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429)

DEFF Research Database (Denmark)

EFSA Panel on Animal Health and Welfare; More, Simon J.; Bøtner, Anette

2017-01-01

Anthrax has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of anthrax to be listed, Article 9 for the categorisation of anthrax according to disease prevention and control rul...... species to be listed for anthrax according to Article 8(3) are several species of mammals, birds and reptiles, and susceptible herbivores and pigs as reservoir....

Evaluation of personal inhalable aerosol samplers with different filters for use during anthrax responses.

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Grinshpun, Sergey A; Weber, Angela M; Yermakov, Michael; Indugula, Reshmi; Elmashae, Yousef; Reponen, Tiina; Rose, Laura

2017-08-01

Risk of inhalation exposure to viable Bacillus anthracis (B. anthracis) spores has primarily been assessed using short-term, stationary sampling methods which may not accurately characterize the concentration of inhalable-sized spores reaching a person's breathing zone. While a variety of aerosol sampling methods have been utilized during previous anthrax responses, no consensus has yet been established for personal air sampling. The goal of this study was to determine the best sampler-filter combination(s) for the collection and extraction of B. anthracis spores. The study was designed to (1) evaluate the performance of four filter types (one mixed cellulose ester, MCE (pore size = 3 µm), two polytetrafluoroethylene, PTFE (1 and 3 µm), and one polycarbonate, PC (3 µm)); and (2) evaluate the best performing filters in two commercially available inhalable aerosol samplers (IOM and Button). Bacillus thuringiensis kurstaki [Bt(k)], a simulant for B. anthracis, served as the aerosol challenge. The filters were assessed based on criteria such as ability to maintain low pressure drop over an extended sampling period, filter integrity under various environmental conditions, spore collection and extraction efficiencies, ease of loading and unloading the filters into the samplers, cost, and availability. Three of the four tested collection filters-except MCE-were found suitable for efficient collection and recovery of Bt(k) spores sampled from dry and humid as well as dusty and clean air environments for up to 8 hr. The PC (3 µm) filter was identified as the best performing filter in this study. The PTFE (3 µm) demonstrated a comparable performance, but it is more expensive. Slightly higher concentrations were measured with the IOM inhalable sampler which is the preferred sampler's performance criterion when detecting a highly pathogenic agent with no established "safe" inhalation exposure level. Additional studies are needed to address the effects of

Anthrax lethal toxin inhibits translation of hypoxia-inducible factor 1α and causes decreased tolerance to hypoxic stress.

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Ouyang, Weiming; Torigoe, Chikako; Fang, Hui; Xie, Tao; Frucht, David M

2014-02-14

Hypoxia is considered to be a contributor to the pathology associated with administration of anthrax lethal toxin (LT). However, we report here that serum lactate levels in LT-treated mice are reduced, a finding inconsistent with the anaerobic metabolism expected to occur during hypoxia. Reduced lactate levels are also observed in the culture supernatants of LT-treated cells. LT inhibits the accumulation of hypoxia-inducible factor (HIF)-1α, a subunit of HIF-1, the master regulator directing cellular responses to hypoxia. The toxin has no effect on the transcription or protein turnover of HIF-1α, but instead it acts to inhibit HIF-1α translation. LT treatment diminishes phosphorylation of eIF4B, eIF4E, and rpS6, critical components of the intracellular machinery required for HIF-1α translation. Moreover, blockade of MKK1/2-ERK1/2, but not p38 or JNK signaling, lowers HIF-1α protein levels in both normoxic and hypoxic conditions, consistent with a role for MKK1 and MKK2 as the major targets of LT responsible for the inhibition of HIF-1α translation. The physiological importance of the LT-induced translation blockade is demonstrated by the finding that LT treatment decreases the survival of hepatocyte cell lines grown in hypoxic conditions, an effect that is overcome by preinduction of HIF-1α. Taken together, these data support a role for LT in dysregulating HIF-1α and thereby disrupting homeostatic responses to hypoxia, an environmental characteristic of certain tissues at baseline and/or during disseminated infection with Bacillus anthracis.

Bacillus anthracis infections – new possibilities of treatment

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Dorota Żakowska

2015-05-01

Full Text Available [b]Introduction and objective[/b]. [i]Bacillus anthracis[/i] is one of biological agents which may be used in bioterrorism attacks. The aim of this study a review of the new treatment possibilities of anthrax, with particular emphasis on the treatment of pulmonary anthrax. [b]Abbreviated description of the state of knowledge[/b]. Pulmonary anthrax, as the most dangerous clinical form of the disease, is also extremely difficult to treat. Recently, considerable progress in finding new drugs and suitable therapy for anthrax has been achieved, for example, new antibiotics worth to mentioning, levofloxacin, daptomycin, gatifloxacin and dalbavancin. However, alternative therapeutic options should also be considered, among them the antimicrobial peptides, characterized by lack of inducible mechanisms of pathogen resistance. Very promising research considers bacteriophages lytic enzymes against selected bacteria species, including antibiotic-resistant strains. [b]Results[/b]. Interesting results were obtained using monoclonal antibodies: raxibacumab, cAb29 or cocktails of antibodies. The application of CpG oligodeoxynucleotides to boost the immune response elicited by Anthrax Vaccine Adsorbed and CMG2 protein complexes, also produced satisfying therapy results. Furthermore, the IFN-α and IFN-β, PA-dominant negative mutant, human inter-alpha inhibitor proteins and LF inhibitors in combination with ciprofloxacin, also showed very promising results. [b]Conclusions[/b]. Recently, progress has been achieved in inhalation anthrax treatment. The most promising new possibilities include: new antibiotics, peptides and bacteriophages enzymes, monoclonal antibodies, antigen PA mutants, and inter alpha inhibitors applications. In the case of the possibility of bioterrorist attacks, the examination of inhalation anthrax treatment should be intensively continued.

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

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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.

Molecular epidemiology of anthrax cases associated with recreational use of animal hides and yarn in the United States.

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Chung K Marston

Full Text Available To determine potential links between the clinical isolate to animal products and their geographic origin, we genotyped (MLVA-8, MVLA-15, and canSNP analysis 80 environmental and 12 clinical isolates and 2 clinical specimens from five cases of anthrax (California in 1976 [n = 1], New York in 2006 [n = 1], Connecticut in 2007 [n = 2], and New Hampshire in 2009[n = 1] resulting from recreational handling of animal products. For the California case, four clinical isolates were identified as MLVA-8 genotype (GT 76 and in the canSNP A.Br.Vollum lineage, which is consistent with the Pakistani origin of the yarn. Twenty eight of the California isolates were in the A.Br.Vollum canSNP lineage and one isolate was in the A.Br. 003/004 canSNP sub-group. All 52 isolates and both clinical specimens related to the New York and Connecticut cases were MLVA-8 GT 1. The animal products associated with the NY and CT cases were believed to originate from West Africa, but no isolates from this region are available to be genotyped for comparison. All isolates associated with the New Hampshire case were identical and had a new genotype (GT 149. Isolates from the NY, CT and NH cases diverge from the established canSNP phylogeny near the base of the A.Br.011/009. This report illustrates the power of the current genotyping methods and the dramatically different epidemiological conditions that can lead to infections (i.e., contamination by a single genotype versus widespread contamination of numerous genotypes. These cases illustrate the need to acquire and genotype global isolates so that accurate assignments can be made about isolate origins.

A Dual Role for the Bacillus anthracis Master Virulence Regulator AtxA: Control of Sporulation and Anthrax Toxin Production.

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Dale, Jennifer L; Raynor, Malik J; Ty, Maureen C; Hadjifrangiskou, Maria; Koehler, Theresa M

2018-01-01

Bacillus anthracis is an endemic soil bacterium that exhibits two different lifestyles. In the soil environment, B. anthracis undergoes a cycle of saprophytic growth, sporulation, and germination. In mammalian hosts, the pathogenic lifestyle of B. anthracis is spore germination followed by vegetative cell replication, but cells do not sporulate. During infection, and in specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA. A critical role for the atxA gene in B. anthracis virulence has been established. Here we report an inverse relationship between toxin production and sporulation that is linked to AtxA levels. During culture in conditions favoring sporulation, B. anthracis produces little to no AtxA. When B. anthracis is cultured in conditions favoring toxin gene expression, AtxA is expressed at relatively high levels and sporulation rate and efficiency are reduced. We found that a mutation within the atxA promoter region resulting in AtxA over-expression leads to a marked sporulation defect. The sporulation phenotype of the mutant is dependent upon pXO2-0075 , an atxA -regulated open reading frame located on virulence plasmid pXO2. The predicted amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain of sporulation sensor histidine kinases. It was shown previously that pXO2-0075 overexpression suppresses sporulation. We have designated pXO2-0075 " skiA " for "sporulation kinase inhibitor." Our results indicate that in addition to serving as a positive regulator of virulence gene expression, AtxA modulates B. anthracis development.

Cutaneous anthrax in Lima, Peru: retrospective analysis of 71 cases, including four with a meningoencephalic complication Ántrax cutáneo en Lima, Perú: análisis retrospectivo de 71 casos, incluyendo cuatro con complicación meningoencefálica

Directory of Open Access Journals (Sweden)

Ciro Maguiña

2005-02-01

Full Text Available Anthrax is a zoonosis produced by Bacillus anthracis, and as an human infection is endemic in several areas in the world, including Peru. More than 95% of the reported naturally acquired infections are cutaneous, and approximately 5% of them can progress to meningoencephalitis. In this study we review the clinical and epidemiological characteristics of the patients with diagnosis of cutaneous anthrax evaluated between 1969 and 2002 at the Hospital Nacional Cayetano Heredia (HNCH and the Instituto de Medicina Tropical Alexander von Humboldt in Lima, Peru. Seventy one patients were included [49/71 (69% of them men], with a mean age of 37 years. The diagnoses were classified as definitive (44% or probable (56%. The most common occupation of the patients was agriculture (39%. The source of infection was found in 63 (88.7% patients. All the patients had ulcerative lesions, with a central necrosis. Most of the patients (65% had several lesions, mainly located in the upper limbs (80%. Four patients (5.6% developed meningoencephalitis, and three of them eventually died. In conclusion, considering its clinical and epidemiological characteristics, cutaneous anthrax must be included in the differential diagnosis of skin ulcers. A patient with clinical suspicion of the disease should receive effective treatment soon, in order to avoid neurological complications which carry a high fatality rate.El ántrax es una zoonosis producida por el Bacillus anthracis y la infección humana es endémica en diversas partes del mundo, incluyendo el Perú. Más del 95% de las infecciones adquiridas naturalmente son cutáneas y aproximadamente 5% de ellas pueden evolucionar para meningoencefalitis. En este estudio revisamos las características clínicas y epidemiológicas de los pacientes con diagnóstico de ántrax cutáneo evaluados entre 1969 y 2002 en el Hospital Nacional Cayetano Heredia (HNCH y en el Instituto de Medicina Tropical Alexander von Humboldt, en Lima, Per

Stability analysis model of Bacillus antracis using SEIQR population compartment with quarantine in Indonesia

Science.gov (United States)

Saptaningtyas, F. Y.; Prihantini

2018-03-01

In Indonesia there are many breeders of cattle that are actually used as a livelihood so that Indonesia is prone to the spread of anthrax disease. This disease can be transmitted through indirect contacts such as deep impurities, saliva and the like. Anthrax disease is a type of disease caused by bacteria and there is a link between livestock and humans as the host. Anthrax disease with quarantine special factors can be modelled with SEIQR where existed from susceptible, exposed, symptomatic infected, quarantine and recovered compartment with research method used that is quantitative method, so different with disease models caused by bacteria in general.In this study we will determine the qualitative analysis of the anthrax disease distribution model with goal of research are to obtain model transmission Anthrax, to find equilibrium point of model and to find the basic reproduction number R 0, where R0 aims to determine the spread of disease or the absence of disease spread through endemic equilibrium stability analysis. The goal from this research is compare stability analysis between model with quarantine and model without quarantine use Routh-Hurwitz criteria to prove that E 1 and E 2 are asymptotic stability equilibrium so from this research conclude that quarantine population can speed up recovered population to be free disease condition from Anthrax.

History of Bioterrorism: Botulism

Medline Plus

Full Text Available ... Compartir This video describes the Category A diseases: smallpox, anthrax, botulism, plague, tularemia, and viral hemorrhagic fevers. ... Specific Segments of the Program Overview Anthrax Plague Smallpox Botulism Viral Hemorrhagic Fevers Tularemia Note: Parts of ...

History of Bioterrorism: Botulism

Medline Plus

Full Text Available ... describes the Category A diseases: smallpox, anthrax, botulism, plague, tularemia, and viral hemorrhagic fevers. If these germs ... Watch Specific Segments of the Program Overview Anthrax Plague Smallpox Botulism Viral Hemorrhagic Fevers Tularemia Note: Parts ...

History of Bioterrorism: Botulism

Medline Plus

Full Text Available ... the Category A diseases: smallpox, anthrax, botulism, plague, tularemia, and viral hemorrhagic fevers. If these germs were ... Overview Anthrax Plague Smallpox Botulism Viral Hemorrhagic Fevers Tularemia Note: Parts of this video were adapted from " ...

Anthrax

Science.gov (United States)

2009-01-01

chest radiograph will almost always exhibit a widened mediastinal contour that includes unilat- eral or bilateral hilar enlargement , as. well as...express B-Iactamase variants, peni - cillinases and cephalosporinases, which would undermine a lone-penicillin therapy (Lightfoot et ai., 1990

Epidemiology of bacterial zoonoses in Nigeria | Adesiji | Nigerian ...

African Journals Online (AJOL)

This paper dicusses the epidemiology and epizootiology of bacterial zoonotic diseases in Nigeria. Six diseases are discussed including anthrax, brucellosis, bovine tuberculosis, campylobacteriosis leptospirosis, salmonellosis and tetanus. All axcept anthrax are enzootic and endemic in the country, and have been ...

Uniformed Services University of the Health Sciences Journal 2003 Edition

Science.gov (United States)

2004-08-18

Building 53 ..............................................................................158 - Heating/Ventilation/Air Conditioning ( HVAC ) Replacement...Surrogates for Bacillus anthracis - October 9-10, 2002 ....................................454 - Support to the European Union on Medical Preparedness for...radiation necessary to eradicate anthrax spores ; the researchers use a harmless surrogate spore that mimics the biological properties of live anthrax

Bacillus anthracis infections – new possibilities of treatment

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Dorota Żakowska

2015-05-01

Recently, progress has been achieved in inhalation anthrax treatment. The most promising new possibilities include: new antibiotics, peptides and bacteriophages enzymes, monoclonal antibodies, antigen PA mutants, and inter alpha inhibitors applications. In the case of the possibility of bioterrorist attacks, the examination of inhalation anthrax treatment should be intensively continued.

Ciprofloxacin and Pregnancy

Science.gov (United States)

... anthrax you have is not treatable with other antibiotics, it is likely that the benefits of treating an anthrax infection outweigh the risk ... a small number of studies and the known benefits of breastfeeding. In a study of 10 ... of a better studied antibiotic to treat your infection with your health care ...

Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil.

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Brian France

Full Text Available Any release of anthrax spores in the U.S. would require action to decontaminate the site and restore its use and operations as rapidly as possible. The remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping and post-decon to determine that the site is free of contamination (clearance sampling. Whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples can become the factor that limits the pace of restoring operations. To address this sampling and analysis bottleneck and decrease the time needed to recover from an anthrax contamination event, this study investigates the use of composite sampling. Pooling or compositing of samples is an established technique to reduce the number of analyses required, and its use for anthrax spore sampling has recently been investigated. However, use of composite sampling in an anthrax spore remediation event will require well-documented and accepted methods. In particular, previous composite sampling studies have focused on sampling from hard surfaces; data on soil sampling are required to extend the procedure to outdoor use. Further, we must consider whether combining liquid samples, thus increasing the volume, lowers the sensitivity of detection and produces false negatives. In this study, methods to composite bacterial spore samples from soil are demonstrated. B. subtilis spore suspensions were used as a surrogate for anthrax spores. Two soils (Arizona Test Dust and sterilized potting soil were contaminated and spore recovery with composites was shown to match individual sample performance. Results show that dilution can be overcome by concentrating bacterial spores using standard filtration methods. This study shows that composite sampling can be a viable method of pooling samples to reduce the number of analysis that must be performed during anthrax spore remediation.

McCormick's Mayhem: "The Time To Learn To Dance Is Not Five Minutes before the Party." School Crisis Management Case Study.

Science.gov (United States)

Bouleris, Sue; Collett, De Ette; Mauntler, Mike; Ray, Shirley

This paper discusses the importance of a school's having procedures in place to deal with possible biological terrorist threats. It begins with a discussion of biological terrorism. It then provides the symptoms of anthrax, treatment options for anthrax, and precautions to take when suspicious of an attack with a hazardous material. The paper goes…

A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

Science.gov (United States)

Herrera, Bobby Brooke; Hamel, Donald J; Oshun, Philip; Akinsola, Rolake; Akanmu, Alani S; Chang, Charlotte A; Eromon, Philomena; Folarin, Onikepe; Adeyemi, Kayode T; Happi, Christian T; Lu, Yichen; Ogunsola, Folasade; Kanki, Phyllis J

2018-05-01

Ebola virus (EBOV) caused more than 11,000 deaths during the 2013-2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses. Between August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors. Our data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.

Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

Science.gov (United States)

Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

2006-11-17

The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

Key Planning Factors for Recovery from a Biological Terrorism Incident

Science.gov (United States)

2012-08-30

number of people (particularly the elderly, very young, and immunocompromised ) may become ill from an exposure as small as 2 to 4 spores (based of...Gastrointestinal anthrax requires spores to be ingested. If untreated, mortality also is very high, but with antibiotic treatment mortality rates are low...anthrax cases (although in fewer numbers). Prophylaxis ( antibiotics ) and vaccines are available for most strains of Bacillus anthracis. The

2010 Joint Chemical Biological Radiological Nuclear (CBRN) Conference and Exhibition (BRIEFING CHARTS)

Science.gov (United States)

2010-06-24

Gray water re-use for lavatories – 50 State EPA legal over ground dumping per manufacturer • Automated HVAC /Pressure System – BSL 2+/admin/Clean...LD50 reached within 1 minute using crude preparation of BG spores (10E8 concentration) • Particle size, velocity, and concentration measurements...Al Qaeda training camp, Kandahar, Afghanistan Aum Shinrikyo headquarters Bacillus anthrax Anthrax Spraying, Tokyo http://www.cdc.gov/ncidod/ EID

Evaluation of Expedient Decontamination Options with Activated Peroxide-based Liquid Sporicides

Science.gov (United States)

2013-02-05

Figure 2-1) that are typical of the materials found in residential dwellings and meet industry standards or specifications for indoor use. Documented...Anthrax inhalation and lethal human infection. Lancet, 2002. 359(9307): p. 710-1. 14. Glassman, H.N., Industrial inhalation anthrax. Bacteriol. Rev...Begin by donning PPE (gloves, lab coat, and protective eyewear ). 2. Clean the workspace by wiping with pAB, next with DI water , and lastly with a 70

Specialized Regional National Guard Brigades - The Army’s Federal Disaster Response Force

Science.gov (United States)

2003-04-24

into the Pentagon and of Anthrax spores being sent to congressional buildings in the DC area, most would just think you were being a bit extreme...Chapter 9&10. 20 “A foreign terrorist organization smuggles anthrax bacillus into the United States and places it in the heating, ventilating, and air...conditioning ( HVAC ) ducting at an indoor sports arena, exposing some 17,000 in attendance at a hockey game. The game concludes without incident and the

Whole-Genome Sequences of 94 Environmental Isolates of Bacillus cereus Sensu Lato

Science.gov (United States)

Feldgarden, Michael; Kolter, Roberto; Mahillon, Jacques

2013-01-01

Bacillus cereus sensu lato is a species complex that includes the anthrax pathogen Bacillus anthracis and other bacterial species of medical, industrial, and ecological importance. Their phenotypes of interest are typically linked to large plasmids that are closely related to the anthrax plasmids pXO1 and pXO2. Here, we present the draft genome sequences of 94 isolates of B. cereus sensu lato, which were chosen for their plasmid content and environmental origins. PMID:24092776

Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh.

Science.gov (United States)

Rume, Farzana Islam; Affuso, Alessia; Serrecchia, Luigina; Rondinone, Valeria; Manzulli, Viviana; Campese, Emanuele; Di Taranto, Pietro; Biswas, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Yasmin, Mahmuda; Fasanella, Antonio; Hugh-Jones, Martin

2016-01-01

In Bangladesh, anthrax, caused by the bacterium Bacillus anthracis, is considered an endemic disease affecting ruminants with sporadic zoonotic occurrences in humans. Due to the lack of knowledge about risks from an incorrect removal of infected carcasses, the disease is not properly monitored, and because of the socio-economic conditions, the situation is under-reported and under-diagnosed. For sensitive species, anthrax represents a fatal outcome with sudden death and sometimes bleeding from natural orifices. The most common source of infection for ruminants is ingestion of spores during grazing in contaminated pastures or through grass and water contaminated with anthrax spores. Domestic cattle, sheep and goats can also become infected through contaminated bone meal (used as feed) originating from anthrax-infected carcasses. The present investigation was conducted to isolate B. anthracis organisms from 169 samples (73 soil, 1 tissue, 4 bone and 91 bone meal samples) collected from 12 different districts of Bangladesh. The sampling was carried out from 2012 to 2015. Twelve samples resulted positive for B. anthracis. Biomolecular analyses were conducted starting from the Canonical Single Nucleotide Polymorphism (CanSNP) to analyze the phylogenetic origin of strains. The analysis of genotype, obtained through the Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) with the analysis of 15 Variable Number Tandem Repeats (VNTR), demonstrated four different genotypes: two of them were previously identified in the district of Sirajganj. The sub-genotyping, conducted with Single Nucleotide Repeats analysis, revealed the presence of eight subgenotypes. The data of the present study concluded that there was no observed correlation between imported cattle feed and anthrax occurrence in Bangladesh and that the remarkable genetic variations of B. anthracis were found in the soil of numerous outbreaks in this country.

Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh.

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Farzana Islam Rume

Full Text Available In Bangladesh, anthrax, caused by the bacterium Bacillus anthracis, is considered an endemic disease affecting ruminants with sporadic zoonotic occurrences in humans. Due to the lack of knowledge about risks from an incorrect removal of infected carcasses, the disease is not properly monitored, and because of the socio-economic conditions, the situation is under-reported and under-diagnosed. For sensitive species, anthrax represents a fatal outcome with sudden death and sometimes bleeding from natural orifices. The most common source of infection for ruminants is ingestion of spores during grazing in contaminated pastures or through grass and water contaminated with anthrax spores. Domestic cattle, sheep and goats can also become infected through contaminated bone meal (used as feed originating from anthrax-infected carcasses. The present investigation was conducted to isolate B. anthracis organisms from 169 samples (73 soil, 1 tissue, 4 bone and 91 bone meal samples collected from 12 different districts of Bangladesh. The sampling was carried out from 2012 to 2015. Twelve samples resulted positive for B. anthracis. Biomolecular analyses were conducted starting from the Canonical Single Nucleotide Polymorphism (CanSNP to analyze the phylogenetic origin of strains. The analysis of genotype, obtained through the Multiple Locus Variable Number Tandem Repeat Analysis (MLVA with the analysis of 15 Variable Number Tandem Repeats (VNTR, demonstrated four different genotypes: two of them were previously identified in the district of Sirajganj. The sub-genotyping, conducted with Single Nucleotide Repeats analysis, revealed the presence of eight subgenotypes. The data of the present study concluded that there was no observed correlation between imported cattle feed and anthrax occurrence in Bangladesh and that the remarkable genetic variations of B. anthracis were found in the soil of numerous outbreaks in this country.

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro

Science.gov (United States)

2013-03-11

sterile screw-capped tube containing 5 ml of sterile PBS. New sporulation medium (3 grams of Tryptone, 3 grams of yeast extract, 2 grams of agar, 23...United States. Emerg Infect Dis 7: 933-944. 3. Penn CC, Klotz SA (1997) Anthrax pneumonia. Semin Respir Infect 12: 28-30. 4. Sweeney DA, Hicks CW, Cui X...Li Y, Eichacker PQ (2011) Anthrax infection. Am J Respir Crit Care Med 184: 1333-1341. 5. Roy CJ, Reed DS, Hutt JA (2010) Aerobiology and inhalation

Assembly and Function of the Bacillus anthracis S-Layer.

Science.gov (United States)

Missiakas, Dominique; Schneewind, Olaf

2017-09-08

Bacillus anthracis, the anthrax agent, is a member of the Bacillus cereus sensu lato group, which includes invasive pathogens of mammals or insects as well as nonpathogenic environmental strains. The genes for anthrax pathogenesis are located on two large virulence plasmids. Similar virulence plasmids have been acquired by other B. cereus strains and enable the pathogenesis of anthrax-like diseases. Among the virulence factors of B. anthracis is the S-layer-associated protein BslA, which endows bacilli with invasive attributes for mammalian hosts. BslA surface display and function are dependent on the bacterial S-layer, whose constituents assemble by binding to the secondary cell wall polysaccharide (SCWP) via S-layer homology (SLH) domains. B. anthracis and other pathogenic B. cereus isolates harbor genes for the secretion of S-layer proteins, for S-layer assembly, and for synthesis of the SCWP. We review here recent insights into the assembly and function of the S-layer and the SCWP.

Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

Science.gov (United States)

Wright, Jennifer G; Plikaytis, Brian D; Rose, Charles E; Parker, Scott D; Babcock, Janiine; Keitel, Wendy; El Sahly, Hana; Poland, Gregory A; Jacobson, Robert M; Keyserling, Harry L; Semenova, Vera A; Li, Han; Schiffer, Jarad; Dababneh, Hanan; Martin, Sandra K; Martin, Stacey W; Marano, Nina; Messonnier, Nancy E; Quinn, Conrad P

2014-02-12

We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at

Development of Protective Immunity in New Zealand White Rabbits Challenged with Bacillus anthracis Spores and Treated with Antibiotics and Obiltoxaximab, a Monoclonal Antibody against Protective Antigen.

Science.gov (United States)

Henning, Lisa N; Carpenter, Sarah; Stark, Gregory V; Serbina, Natalya V

2018-02-01

The recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax protective antigen (PA), is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for the treatment of inhalational anthrax. Because of spore latency, disease reemergence after treatment cessation is a concern, and there is a need to understand the development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in New Zealand White (NZW) rabbits challenged with a targeted lethal dose of Bacillus anthracis spores and treated with antibiotics, obiltoxaximab, or a combination of both. Survivors of the primary challenge were rechallenged 9 months later and monitored for survival. Survival rates after primary and rechallenge for controls and animals treated with obiltoxaximab, levofloxacin, or a combination of both were 0, 65, 100, and 95%, and 0, 100, 95, and 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin-neutralizing titers prior to rechallenge. Following rechallenge, systemic bacteremia and toxemia were not detected in most animals, and the levels of circulating anti-PA IgG titers increased starting at 5 days postrechallenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves the survival of rabbits that received a lethal inhalation B. anthracis spore challenge dose and does not interfere with the development of immunity. Survivors of primary challenge are protected against reexposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response. Copyright © 2018 Henning et al.

First detection of Bacillus anthracis in feces of free-ranging raptors from central Argentina.

Science.gov (United States)

Saggese, Miguel D; Noseda, Ramón P; Uhart, Marcela M; Deem, Sharon L; Ferreyra, Hebe; Romano, Marcelo C; Ferreyra-Armas, María C; Hugh-Jones, Martin

2007-01-01

Prevalence of anthrax spores in feces of raptors was determined from samples collected in November-December 2000 and April-May 2001 in an agricultural region of Santa Fé province, Argentina. Feces were tested from 48 birds of six raptor species. One of 14 chimango caracaras (Milvago chimango) and one of eight road-side hawks (Buteo magnirostris) tested positive. The prevalence of Bacillus anthracis spores in feces for the six species was 4% (n=48). The prevalence was 7% (n=14) for chimango caracaras, 13% for road-side hawks (n=8), and 0% for the remaining species (Burrowing owl [Speotyto cunicularia] [n=17], Swainson's hawk [Buteo swainsoni] [n=3], Aplomado falcon [Falco femoralis] [n=2], and American kestrel [Falco sparverius] [n=4]). Grouped by their feeding habits, prevalence for scavenger species was not significantly different than for predators (7% vs. 3%, P>0.999). This study provides evidence that in central Argentina scavenger and non-scavenger raptors may have a role in the epidemiology of anthrax. Long-term studies to determine the extent of this potential involvement in the epidemiology of anthrax in central Argentina are required.

Worldwide Report, Epidemiology, No. 327

National Research Council Canada - National Science Library

1983-01-01

..., Chickenpox, Measles, Eye Diseases, Dengue Fever, Infection, Meningitis, Death, Cancer, Children's Hospitals, Medical Supplies, Medical Equipment, Anthrax, Pneumonia Cases, Food Shortages, Herpes, Youth...

Uso de la vacuna contra el carbunco en los Estados Unidos de América

Directory of Open Access Journals (Sweden)

Full Text Available This piece presents the recommendations of the Advisory Committee on Immunization Practices of the United States of America concerning the use of aluminum hydroxide adsorbed cell-free anthrax vaccine (Anthrax Vaccine Adsorbed, or AVA and the use of chemoprophylaxis against Bacillus anthracis in the United States. The recommended vaccination schedule consists of three subcutaneous injections, at 0, 2, and 4 weeks, and three booster vaccinations, at 6, 12, and 18 months. To maintain immunity, an annual booster injection is recommended. Approximately 95% of vaccinees seroconvert, with a fourfold rise in anti-PA (protective antigen IgG titers after three doses. Analysis of data from the United States' Vaccine Adverse Event Reporting System has documented no pattern of serious adverse events clearly associated with the vaccine, except injection-site reactions. Vaccination is contraindicated in the case of a previous history of anthrax infection or anaphylactic reaction following a previous dose of AVA or any of the vaccine components. In addition, vaccination should be postponed in the case of moderate or severe acute illness. Pregnant women should be vaccinated against anthrax only if the potential benefits of vaccination outweigh the potential risks to the fetus. Vaccination during breast-feeding is not medically contraindicated. Routine preexposure vaccination with AVA is indicated for persons engaged in: a work involving production quantities or concentrations of B. anthracis cultures or b activities with a high potential for aerosol production. For the military and other select populations or for groups for which a calculable risk can be assessed, preexposure vaccination may be indicated. Following confirmed or suspected exposure to B. anthracis, postexposure antibiotic prophylaxis should be administered with ciprofloxacin, ofloxacin, doxycycline, penicillin VK, or amoxicillin. If the vaccine is available, prophylaxis should continue for 4 weeks

NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

Directory of Open Access Journals (Sweden)

Onkar Sharma

2016-03-01

Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

JPRS Report, Epidemiology

National Research Council Canada - National Science Library

1989-01-01

Partial Contents: SubSaharan Africa, Drugs, Heart Diseases, Malaria, Death, Influenza Virus, Animal Diseases, Fevers, Cholera, Anthrax, Dengue, Public health, Hemorrhagic fever, Cancer, Meningitis, Death, Salmonella...

The reporting of a Bacillus anthracis B-clade strain in South Africa after more than 20 years.

Science.gov (United States)

Lekota, K E; Hassim, A; Rogers, P; Dekker, E H; Last, R; de Klerk-Lorist, L; van Heerden, H

2018-05-02

Anthrax is a disease with an age old history in Africa caused by the Gram-positive endospore forming soil bacterium Bacillus anthracis. Epizootics of wild ungulates occur annually in the enzootic region of Pafuri, Kruger National Park (KNP) in the Limpopo Province of South Africa. Rigorous routine surveillance and diagnostics in KNP, has not revealed these rare isolates since the 1990s, despite unabated annual outbreaks. In 2011 a cheetah was diagnosed as anthrax positive from a private game reserve in Limpopo Province and reported to State Veterinary Services for further investigation. Isolation, molecular diagnostics, whole genome sequencing and comparative genomics were carried out for B. anthracis KC2011. Bacteriological and molecular diagnostics confirmed the isolate as B. anthracis. Subsequent typing and whole genome single nucleotide polymorphisms analysis indicated it clustered alongside B. anthracis SA A0091 in the B.Br.010 SNP branch. Unlike B. anthracis KrugerB strain, KC2011 strain has unique SNPs and represents a new branch in the B-clade. The isolation and genotypic characterisation of KC2011 demonstrates a gap in the reporting of anthrax outbreaks in the greater Limpopo province area. The identification of vulnerable and susceptible cheetah mortalities due to this strain has implications for conservation measures and disease control.

Vaporized Hydrogen Peroxide (VHP) Decontamination of VX, GD, and HD

National Research Council Canada - National Science Library

Wagner, George W; Sorrick, David C; Procell, Lawrence R; Hess, Zoe A; Brickhouse, Mark D; McVey, Iain F; Schwartz, Lewis I

2003-01-01

Vaporized Hydrogen Peroxide (VHP) has been utilized for more than a decade to sterilize clean rooms and pharmaceutical processing equipment and, quite recently, to decontaminate anthrax-ridden buildings...

Microarray Analysis of Transposon Insertion Mutants in Bacillus Anthracis: Global Identification of Genes Required for Sporulation and Germination

National Research Council Canada - National Science Library

Day , Jr., William A; Rasmussen, Suzanne L; Carpenter, Beth M; Peterson, Scott N; Friedlander, Arthur M

2007-01-01

.... The system, used to identify genes required for generation of the infectious anthrax spore, spore germination and optimal growth on rich medium, was predictive of the contribution of two conserved...

A Bioterrorism Prevention Strategy for the 21st Century

National Research Council Canada - National Science Library

Lein, Brian

2003-01-01

.... The results of the anthrax attack and multiple wargames revealed that the United States is currently ill prepared to prevent or deter a bioterrorism attack against it's homeland and protect the citizens...

JPRS Report, Epidemiology

National Research Council Canada - National Science Library

1993-01-01

Partial Contents: Cholera Outbreak in Busia District, Guinea Worm Eradication Proceeding Well, Eight Die From Yellow Fever in Oyo, Cholera Spread To All Parts of Country, Statistics on Cholera Deaths Issued, Anthrax...

Responding to the Threat of Weapons of Mass Destruction After September 11, 2001

National Research Council Canada - National Science Library

Lewy, Donald

2002-01-01

This paper addresses the threat posed by weapons of mass destruction as it is understood following the events of 11 September 2001 and the anthrax attacks directed at congressional and media offices...

The USEPA environmental response team TAGA at work at the Hart building fumigation

Energy Technology Data Exchange (ETDEWEB)

Mickunas, D.B.; Turpin, R. [United States Environmental Protection Agency, Edison, NJ (United States). Environmental Response Team; Blaze, S.; Wood, J. [Lockheed Martin Inc., Edison, NJ (United States). Response Engineering and Analytical Contract

2004-07-01

This paper describes the fumigation activities conducted at the Hart Senate Office building in Washington, DC in October 2001 following the delivery of a letter containing anthrax. Anthrax spores were dispersed in areas within the office. The United States States Environmental Protection Agency Environmental Response Team (USEPA/ERT) was responsible for the decontamination activities. Chlorine dioxide was chosen as the anthrax sporicide after a detailed technical review and consultation with scientific experts. ERT provided continuous, near real-time ambient air monitoring during the fumigation process. The monitoring was conducted to ensure that the nearby residences were not impacted by the chlorine dioxide fumigant. The monitoring plan required the use of a Trace Atmospheric Gas Analyzer (TAGA), a triple quadrupole mass spectrometer mounted in a mobile laboratory. The monitoring activities of ERT's mobile laboratory were outlined in this paper along with the logistical and technical aspects of the air monitoring. More than 130 hours of TAGA monitoring was performed and 2.3 million data points were collected. No chlorine or chlorine dioxide concentrations were observed above the action limits during any fumigation event. The building was cleared by the health and regulatory agencies and re-opened in January 2002. It was concluded that TAGA is an excellent technology to monitor these compounds because is is extremely sensitive and selective. 2 tabs., 5 figs.

Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (l-Ala-P)

International Nuclear Information System (INIS)

Au, Kinfai; Ren, Jingshan; Walter, Thomas S.; Harlos, Karl; Nettleship, Joanne E.; Owens, Raymond J.; Stuart, David I.; Esnouf, Robert M.

2008-01-01

Structures of BA0252, an alanine racemase from B. anthracis, in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) and determined by X-ray crystallography to resolutions of 2.1 and 1.47 Å, respectively, are described. Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) have determined by X-ray crystallo@@graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties in crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is d-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of l-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies

A Study on molecular characterization of Razi Bacillus anthracis Sterne 34F2 substrain in Iran

Directory of Open Access Journals (Sweden)

Tadayon, K.

2016-07-01

Full Text Available Anthrax, a zoonotic disease caused by Bacillus anthracis, has affected humans since ancient times. For genomic characterization of Razi B. anthracis Sterne 34F2 substrain, single nucleotide polymorphism (SNP genotyping method developed by Van Erth, variable-number tandem-repeat (VNTR-8 analysis proposed by Keim, and multiple-locus VNTR analysis (MLVA-3 introduced by Levy were employed. In the SNPs typing system, where the nucleotide content of the genome at 13 evolutionary canonical loci was collectively analyzed, the originally South African 34F2 substrain was categorized in the A.Br.001/002 subgroup. In the VNTR-8 analysis, fragments with lengths of 314, 229, 162, 580, 532, 158, and 137 bp were identified at the following loci: vrrA, vrrB1, vrrB2, vrrC1, vrrC2, CG3, and pxO1, respectively. In addition, application of Levy's MLVA-3 genotyping method revealed that the genome of this strain carried 941, 451, and 864 bp fragments at AA03, AJ03, and AA07 loci, respectively. The present findings are undoubtedly helpful in meeting the requirements set by the World Organization for Animal Health (OIE and World Health Organization (WHO for anthrax vaccine manufacturers including Razi Institute. However, further similar studies are required to promote the current epidemiological knowledge of anthrax in Iran.

Naturally acquired antibodies to Bacillus anthracis protective antigen in vultures of southern Africa

Directory of Open Access Journals (Sweden)

P. C.B. Turnbull

2008-08-01

Full Text Available TURNBULLP, P.C.B. DIEKMANNM,M., KILIAN, J.W., VERSFELDW, W.,DE VOS, V., ARNTZENL, L.,WOLTER, K., BARTELS, P. & KOTZE, A. 2008.N aturally acquired antibodies to Bacillusa nthracisp rotective antigeni n vultureso f southern Africa. Onderstepoort Journal of Veterinary Research, T5:95-102 Sera from 19 wild caught vultures in northern Namibia and 15 (12 wild caught and three captive bred but with minimal histories in North West Province, South Africa, were examined by an enzyme-linked immunosorbenats say( ELISAf or antibodiesto the Bacillus anthracis toxin protective antigen (PA. As assessed from the baseline established with a control group of ten captive reared vultures with well-documented histories, elevated titres were found in 12 of the 19 (63% wild caught Namibian birds as compared with none of the 15 South African ones. There was a highly significant difference between the Namibian group as a hole and the other groups (P 0.05. Numbers in the Namibian group were too small to determine any significances in species-, sex- or age-related differences within the raw data showing elevated titres in four out of six Cape Vultures, Gyps coprotheress, six out of ten Whitebacked Vultures, Gyps africanus, and one out of three Lappet-faced Vultures, Aegypiust racheliotus, or in five of six males versus three of seven females, and ten of 15 adults versus one of four juveniles. The results are in line with the available data on the incidence of anthrax in northern Namibia and South Africa and the likely contact of the vultures tested with anthrax carcasses. lt is not known whether elevated titre indicates infection per se in vultures or absorption of incompletely digested epitopes of the toxin or both. The results are discussed in relation to distances travelled by vultures as determined by new tracking techniques, how serology can reveal anthrax activity in an area and the issue of the role of vultures in transmission of anthrax.

PENCEGAHAN DAN PEMBERANTASAN PENYAKIT-PENYAKIT ZOONOSA NEW, EMERGING DAN RE-EMERGING DI INDONESIA

Directory of Open Access Journals (Sweden)

Gindo Simanjuntak

2012-09-01

Full Text Available Some important zoonotic diseases in Indonesia are Rabies, Plague, Anthrax, Taeniasis/Cysticercosis and Japanese encephalitis. These diseases are geographycally distributed in some provinces in Indonesia and each disease have its control program. Other zoonoses which are under intensive surveillance are Toxoplasmosis, Leptospirosis, Brucellosis, bovine Tuberculosis and Haemorrhagic Hanta virosis. These diseases have epidemic potential. Plague known foci are in Boyolali Central Java dan Sleman Yogyakarta. In 1987 after 30 years of dormant period an outbreack of plague occured in Pasuruan, East Java with 48 number of cases and 21 deaths. Intensive surveillance on human, rodent and fleas were conducted in three plague foci. Since 1988 no human case of plague is found in Indonesia eventhough antibody against Y. pestis were found positive in human as well as in rodents. Anthrax is distributed geographycally in Jakarta, West Java, Central Java, South Sulawesi, Southeast Sulawesi, West and East Nusa Tenggara and Timor Timur. Skin and intestinal Anthrax types are to be found in Indonesia. In 1990 on outbreak of anthrax occured in Central Java and 7 out of 98 cases were fatal. Of 154 (27.9% out 553 human sera collected from the provinces of West Sumatera, West Kalimantan, South Sulawesi, North Sumatera and North Sulawesi were found positive against toxoplasmosis during the survey conducted in 1995. From the same provinces 152 (19.2% out of 792 animal sera also were found antibody positive against Toxoplasma gondii. There are about 170 Leptospirosis serotypes known in Indonesia. Leptospirosis is geographycally distributed in Central Java, Yogyakarta, West Java, North Sumatera, Riau, Jambi, South Sumatera, Bengkulu, East Kalimantan. Sporadic outbreaks occured in some provinces related to the lack of washing and drinking water in the dry season. Of 10 (1.8% out 154 serum specimens taken from humans in West Sumatera, West Kalimantan, South Sulawesi, North

Bioterrorism

Science.gov (United States)

... Blisters may form, followed by a deep, black scab. The area is usually painless. Gastrointestinal anthrax typically ... agents have also been studied for use as biological weapons, such as tularemia, brucellosis, Q fever, and ...

Sugar-Coated PPE's, Novel Nanomaterial's and Sensing Modules for Disease and Bioterrorism Related Threats

Energy Technology Data Exchange (ETDEWEB)

Bunz, Uwe [Georgia Inst. of Technology, Atlanta, GA (United States)

2003-11-21

The detection and sensing of biological warfare agents (ricin, anthrax toxin), of disease agents (cholera, botulinum, and tetnus toxins, influenza virus, etc.) and of biologically active species important for national security and disease control.

Evaluation of an Anti-rPA IgG ELISA for Measuring the Antibody Response in Mice

National Research Council Canada - National Science Library

Little, S

2004-01-01

A recombinant protective antigen (rPA)-based enzyme-linked immunosorbent assay (ELISA) was developed to measure the serological response of female A/J mice after inoculation with the new rPA-based anthrax vaccine...

Improving Local and State Agency Response to Terrorist Incidents Involving Biological Weapons

National Research Council Canada - National Science Library

2003-01-01

.... Because of multiple terrorist acts such as the September II, 2001 attacks on the Pentagon and the World Trade Center, as well as anthrax contaminated mail and the Oklahoma City bombing, there is a...

Irradiation applications for homeland security

International Nuclear Information System (INIS)

Desrosiers, Marc F.

2004-01-01

In October 2001, first-class mail laced with anthrax was sent to political and media targets resulting in several deaths, illnesses, significant mail-service disruption, and economic loss. The White House Office of Science and Technology Policy established a technical task force on mail decontamination that included three key agencies: National Institute of Standards and Technology with responsibility for radiation dosimetry and coordinating and performing experiments at industrial accelerator facilities; the Armed Forces Radiobiology Research Institute with responsibility for radiobiology; and the US Postal Service with responsibility for radiation-processing quality assurance and quality control. An overview of the anthrax attack decontamination events will be presented as well as expectations for growth in this area and the prospects of other homeland security areas where irradiation technology can be applied

hCG Test (Pregnancy Test)

Science.gov (United States)

... Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer Disease Anemia Angina Ankylosing Spondylitis Anthrax ... Patient Resources For Health Professionals Subscribe Search hCG Pregnancy Send Us Your Feedback Choose Topic At a ...

Modeling an Outbreak of Anthrax

Science.gov (United States)

Sturdivant, Rod; Watts, Krista

2010-01-01

This article presents material that has been used as a classroom activity in a calculus-based probability and statistics course. The application was used in the first few lessons of this course. Students had three previous semesters of math, including calculus (single and multivariable), differential equations, and a course in mathematical…

History of Bioterrorism: Botulism

Medline Plus

Full Text Available ... Facebook Tweet Share Compartir This video describes the Category A diseases: smallpox, anthrax, botulism, plague, tularemia, and ... Medical Research Institute of Infectious Diseases (USAMRIID), the Food and Drug Administration (FDA), and the Centers for ...

History of Bioterrorism: Botulism

Medline Plus

Full Text Available ... Response Worker Health and Safety Reaching At-Risk Populations Health Alert Network (HAN) Laboratory Information Social Media ... Share Compartir This video describes the Category A diseases: smallpox, anthrax, botulism, plague, tularemia, and viral hemorrhagic ...

Seasonal patterns of hormones, macroparasites, and microparasites in wild African ungulates: the interplay among stress, reproduction, and disease.

Directory of Open Access Journals (Sweden)

Carrie A Cizauskas

Full Text Available Sex hormones, reproductive status, and pathogen load all affect stress. Together with stress, these factors can modulate the immune system and affect disease incidence. Thus, it is important to concurrently measure these factors, along with their seasonal fluctuations, to better understand their complex interactions. Using steroid hormone metabolites from fecal samples, we examined seasonal correlations among zebra and springbok stress, reproduction, gastrointestinal (GI parasite infections, and anthrax infection signatures in zebra and springbok in Etosha National Park (ENP, Namibia, and found strong seasonal effects. Infection intensities of all three GI macroparasites examined (strongyle helminths, Strongyloides helminths, and Eimeria coccidia were highest in the wet season, concurrent with the timing of anthrax outbreaks. Parasites also declined with increased acquired immune responses. We found hormonal evidence that both mares and ewes are overwhelmingly seasonal breeders in ENP, and that reproductive hormones are correlated with immunosuppression and higher susceptibility to GI parasite infections. Stress hormones largely peak in the dry season, particularly in zebra, when parasite infection intensities are lowest, and are most strongly correlated with host mid-gestation rather than with parasite infection intensity. Given the evidence that GI parasites can cause host pathology, immunomodulation, and immunosuppression, their persistence in ENP hosts without inducing chronic stress responses supports the hypothesis that hosts are tolerant of their parasites. Such tolerance would help to explain the ubiquity of these organisms in ENP herbivores, even in the face of their potential immunomodulatory trade-offs with anti-anthrax immunity.

Seasonal patterns of hormones, macroparasites, and microparasites in wild African ungulates: the interplay among stress, reproduction, and disease.

Science.gov (United States)

Cizauskas, Carrie A; Turner, Wendy C; Pitts, Neville; Getz, Wayne M

2015-01-01

Sex hormones, reproductive status, and pathogen load all affect stress. Together with stress, these factors can modulate the immune system and affect disease incidence. Thus, it is important to concurrently measure these factors, along with their seasonal fluctuations, to better understand their complex interactions. Using steroid hormone metabolites from fecal samples, we examined seasonal correlations among zebra and springbok stress, reproduction, gastrointestinal (GI) parasite infections, and anthrax infection signatures in zebra and springbok in Etosha National Park (ENP), Namibia, and found strong seasonal effects. Infection intensities of all three GI macroparasites examined (strongyle helminths, Strongyloides helminths, and Eimeria coccidia) were highest in the wet season, concurrent with the timing of anthrax outbreaks. Parasites also declined with increased acquired immune responses. We found hormonal evidence that both mares and ewes are overwhelmingly seasonal breeders in ENP, and that reproductive hormones are correlated with immunosuppression and higher susceptibility to GI parasite infections. Stress hormones largely peak in the dry season, particularly in zebra, when parasite infection intensities are lowest, and are most strongly correlated with host mid-gestation rather than with parasite infection intensity. Given the evidence that GI parasites can cause host pathology, immunomodulation, and immunosuppression, their persistence in ENP hosts without inducing chronic stress responses supports the hypothesis that hosts are tolerant of their parasites. Such tolerance would help to explain the ubiquity of these organisms in ENP herbivores, even in the face of their potential immunomodulatory trade-offs with anti-anthrax immunity.

Method for screening inhibitors of the toxicity of Bacillus anthracis

Science.gov (United States)

Cirino, Nick M.; Jackson, Paul J.; Lehnert, Bruce E.

2001-01-01

The protective antigen (PA) of Bacillus anthracis is integral to the mechanism of anthrax poisoning. The cloning, expression and purification of a 32 kDa B. anthracis PA fragment (PA32) is described. This fragment has also been expressed as a fusion construct to stabilized green fluorescent protein (EGFP-PA32). Both proteins were capable of binding to specific cell surface receptors as determined by fluorescent microscopy and a flow cytometric assay. To confirm binding specificity in the flow cytometric assay, non-fluorescent PA83 or PA32 was used to competitively inhibit fluorescent EGFP-PA32 binding to cell receptors. This assay can be employed as a rapid screen for compounds which disrupts binding of PA to cells. Additionally, the high intracellular expression levels and ease of purification make this recombinant protein an attractive vaccine candidate or therapeutic treatment for anthrax poisoning.

Drug: D02461 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available arditis [DS:H00334] ... semisynthetic penicillin: narrow spectrum penicillin beta-Lac...1531] Pinta [DS:H01530] Diphtheria [DS:H00343] Anthrax [DS:H00328] Rat-bite fever [DS:H01314] Erysipeloid [DS:H01315] Bacterial endoc

ADVANZ – control of neglected zoonotic diseases using one health and ecohealth approaches

DEFF Research Database (Denmark)

Saarnak, Christopher; Mukaratirwa, S.; Johansen, Maria Vang

, echinococcosis, and taeniasis/cysticercosis. Five other diseases have also been declared neglected, i.e. brucellosis, bovine tuberculosis, anthrax, human African trypanosomiasis, and leishmaniasis. The best strategic approach to transmission control and management of these diseases involves integrated One Health...

Browse Title Index

African Journals Online (AJOL)

Items 51 - 100 of 808 ... Vol 53, No 3 (2005), Animal Breeding In Cape Verde: A Retrospective Analysis ... Anthrax in Togo: Spatial Risk in the Savannah Region, Abstract ... use of crop protection products for potential risks to honey bees, Abstract.

U.S. CWMD Coordination

Science.gov (United States)

2012-12-11

coordination. For example, it conducted joint vehicle inspection training for Pakistani Customs and Border Guard personnel at a US- Mexico border...biological material, including such hazards as: anthrax, botulism, cholera , Ebola virus hemorrhagic fever, E. coli, Plague, and smallpox 79

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

Science.gov (United States)

2007-02-01

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

Specialized Veterinary Manpower Needs through 1990,

Science.gov (United States)

1982-01-01

alottg species lines--e.g., canine , feline , and avian medicine. The current trend is toward more group practices, sometimes involving a complete...anthrax, and rabies . Useful assistance to developing countries includes the provision of educational opportunities for their citizens, research in

The future of the public's health in the 21st century

National Research Council Canada - National Science Library

Committee on Assuring the Health of the Public in the 21st Century

The anthrax incidents following the 9/11 terrorist attacks put the spotlight on the nation’s public health agencies, placing it under an unprecedented scrutiny that added new dimensions to the complex issues considered in this report...

Short Communication: Studies of antimicrobial activity and chemical ...

African Journals Online (AJOL)

Chemical constituents of the extract were also determined. The extract of was active against the test organisms including Escherischia coli, Pseudomonas aeruginosa and Candida albicans. Tannins, flavonoids, alkaloids, saponins, anthrax-quinones, starch, general glycosides and bitter principles were found to be present ...

Pan-genome analysis of Senegalese and Gambian strains of ...

African Journals Online (AJOL)

Mbaye

2016-11-09

Nov 9, 2016 ... 1National Laboratory for Research on Animal Diseases (LNERV ... and Rickettssiology, Faculty for Sciences and Technology - Dakar ... stability of its spores, the high level pathogenicity and ... with an anthrax epidemic through an atmospheric .... Characteristics of Bacillus anthracis strains (samples). Code.

Bush will tour Illionois lab working to fight terrorism Argonne develops chemical detectors

CERN Multimedia

2002-01-01

"A chemical sensor that detects cyanide gas, a biochip that can determine the presence of anthrax, and a portable device that finds concealed nuclear materials are among the items scientists at Argonne National Laboratory are working on to combat terrorism" (1/2 page).

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

2016-09-01

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

2016-09-30

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

Science.gov (United States)

Murphy, John R.

2011-01-01

Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

Rapid detection and identification of Bacillus anthracis in food using pyrosequencing technology.

Science.gov (United States)

Amoako, Kingsley K; Janzen, Timothy W; Shields, Michael J; Hahn, Kristen R; Thomas, Matthew C; Goji, Noriko

2013-08-01

The development of advanced methodologies for the detection of Bacillus anthracis has been evolving rapidly since the release of the anthrax spores in the mail in 2001. Recent advances in detection and identification techniques could prove to be an essential component in the defense against biological attacks. Sequence based such as pyrosequencing, which has the capability to determine short DNA stretches in real-time using biotinylated PCR amplicons, has potential biodefense applications. Using markers from the virulence plasmids (pXO1 and pXO2) and chromosomal regions, we have demonstrated the power of this technology in the rapid, specific and sensitive detection of B. anthracis spores in food matrices including milk, juice, bottled water, and processed meat. The combined use of immunomagnetic separation and pyrosequencing showed positive detection when liquid foods (bottled water, milk, juice), and processed meat were experimentally inoculated with 6CFU/mL and 6CFU/g, respectively, without an enrichment step. Pyrosequencing is completed in about 60min (following PCR amplification) and yields accurate and reliable results with an added layer of confidence. The entire assay (from sample preparation to sequencing information) can be completed in about 7.5h. A typical run on food samples yielded 67-80bp reads with 94-100% identity to the expected sequence. This sequence based approach is a novel application for the detection of anthrax spores in food with potential application in foodborne bioterrorism response and biodefense involving the use of anthrax spores. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

78 FR 3440 - Government-Owned Inventions; Availability for Licensing

Science.gov (United States)

2013-01-16

... no vaccine for malaria, and there is growing resistance to existing anti-malarial drugs. Sexual stage... Applications: Malaria vaccine, diagnostic and therapeutic. Competitive Advantages: Single protein malaria... candidate oral anthrax vaccine exists and would result in an easy-to-administer oral delivery system to...

Thermal Inactivation of Bacillus anthracis Spores Using Rapid Resistive Heating

Science.gov (United States)

2016-03-24

agents. There is motivation for using thermal decontamination of B.a. spores for agent defeat scenarios. Spore-forming microorganisms are much...the top soil on Gruinard Island for over 40 years after the British detonated experimental anthrax bombs on the island during World War II (U.S

75 FR 43188 - Request for Public Comment Concerning the Redesign of Statewide Automated Child Welfare...

Science.gov (United States)

2010-07-23

... agencies must build or have a comprehensive IT case management system with centralized, uniform... support the development of efficient, effective, and economical case management systems? 2. How can States... process due to changes in mail handling resulting from the anthrax crisis of October 2001. If you choose...

Prediction of proprotein convertase cleavage sites

DEFF Research Database (Denmark)

Duckert, Peter; Brunak, Søren; Blom, Nikolaj

2004-01-01

by members of the subtilisin/kexin-like proprotein convertase (PC) family. In mammals, seven members have been identified, with furin being the one first discovered and best characterized. Recently, the involvement of furin in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever...

Bacillus Anthracis Spore Interactions with Mammalian Cells: Relationship Between Germination State and the Outcome of in Vitro Infections

Science.gov (United States)

2011-02-28

unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Report Documentation Page Form ApprovedOMB... Peacock S, Belton FC: Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hyg (Lond) 1956, 54(1):28-36. 8. Cleret A

PHYTOCHEMICAL SCREENING AND ANTIMICROBIAL EFFECT ...

African Journals Online (AJOL)

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well as some metabolites such as tannins, saponins, cyanates, oxalate and anthrax- .... production of secondary metabolite in the plant (Waterman & Mole,. 1989).There was no ... positive and gram negative bacteria) and fungi shows its application as a ... marine algae of Visakhapatna city, Andhra Pradesh. Asian Journal.

Expression of the ’Bacillus anthracis’ Protective Antigen Gene by Baculovirus and Vaccinia Virus Recombinants

Science.gov (United States)

1990-02-01

procaryotic systems (12. 45). Certain eucaryotic ically cleaved by a trypsin-like proteas: ito produce a recep- viruses are currently being explored as...19847. Proteolytic activation of anthrax toxin bound to cellular recep- ACKN()WEIX;NMNTS tor%.. p. 111-112. In F. Fehrenbach et al. ifed.). Bacterial

Anthrax carbohydrates, synthesis and uses thereof

Science.gov (United States)

Carlson, Russell W.; Boons, Geert-Jan; Quinn, Conrad; Vasan, Mahalakshmi; Wolfert, Margreet A.; Choudhury, Biswa; Kannenberg, Elmar; Leoff, Christine; Mehta, Alok; Saile, Elke; Rauvolfova, Jana; Wilkins, Patricia; Harvey, Alex J.

2013-04-16

The present invention presents the isolation, characterization and synthesis of oligosaccharides of Bacillus anthracis. Also presented are antibodies that bind to such saccharide moieties and various methods of use for such saccharide moieties and antibodies.

The Seminal Literature of Anthrax Research

Science.gov (United States)

2007-05-01

few days takes a fulminant course, manifested by dyspnea, cough, chills, and a high-grade bac- teremia. Massive hilar adenopathy and mediastinal...causes death of the infected host (Pezard et al. 1991). The genes responsible for capsular biosynthesis (Green, 1985) and the synthesis of LT and ET

Structure of the Anthrax Research Literature

Science.gov (United States)

2006-01-01

46 BARAKAT LA 2002 JAMA-J AM MED ASSOC 287 863 31 READ TD 2003 NATURE 423 81 96 IVANOVA N 2003 NATURE 423 87 73 SCOBIE HM 2003 P NATL ACAD SCI USA...Authors collier, rj 9; leppla, sh 7; young, jat 5; wigelsworth, dj 3; scobie , hm 3; mogridge, j 3; liu, sh 3; liddington, rc 3; lacy, db 3

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African Journals Online (AJOL)

Chirundu, D. Vol 53, No 1-4 (2007) - Articles Schistosomiasis infection among school children in the Zhaugwe resettlement area, Zimbabwe April 2005. Abstract · Vol 55, No 9-12 (2009) - Articles Behavioural factors associated with cutaneous anthrax in Musadzi area of Gokwe North, Zimbabwe Abstract. ISSN: 0008-9176.

Germination of Bacillus cereus spores : the role of germination receptors

NARCIS (Netherlands)

Hornstra, L.M.

2007-01-01

The Bacillus cereus sensu lato group forms a highly homogeneous subdivision of the genus Bacillus and comprises several species that are relevant for humans. Notorious is Bacillus anthracis, the cause of the often-lethal disease anthrax, while the insect pathogen Bacillus