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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erikson, Rebecca L.; Hutchison, Janine R.

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

Terrorism in South Korea.

PubMed

Wang, Soon Joo; Choi, Jin Tae; Arnold, Jeffrey

2003-01-01

South Korea has experienced > 30 suspected terrorism-related events since 1958, including attacks against South Korean citizens in foreign countries. The most common types of terrorism used have included bombings, shootings, hijackings, and kidnappings. Prior to 1990, North Korea was responsible for almost all terrorism-related events inside of South Korea, including multiple assassination attempts on its presidents, regular kidnappings of South Korean fisherman, and several high-profile bombings. Since 1990, most of the terrorist attacks against South Korean citizens have occurred abroad and have been related to the emerging worldwide pattern of terrorism by international terrorist organizations or deranged individuals. The 1988 Seoul Olympic Games provided a major stimulus for South Korea to develop a national emergency response system for terrorism-related events based on the participation of multiple ministries. The 11 September 2001 World Trade Center and Pentagon attacks and the 2001 United States of America (US) anthrax letter attacks prompted South Korea to organize a new national system of emergency response for terrorism-related events. The system is based on five divisions for the response to specific types of terrorist events, involving conventional terrorism, bioterrorism, chemical terrorism, radiological terrorism, and cyber-terrorism. No terrorism-related events occurred during the 2002 World Cup and Asian Games held in South Korea. The emergency management of terrorism-related events in South Korea is adapting to the changing risk of terrorism in the new century.

Vaccines and bioterrorism: smallpox and anthrax.

PubMed

Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

2003-01-01

Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

Judging The Efficacy of Anthrax Fumigations

DTIC Science & Technology

2003-11-20

FUMIGATIONS IN RESPONSE TO 2001 ANTHRAX ATTACKS Most fumigations modeled after biomedical sterilization processes, with established ranges for process...exposure to VHP All BIs recovered aseptically negative for growth of B. stearothermophilus Positive control BIs (5% of BIs) demonstrate growth Negative...of 10 zones was re-fumigated; second fumigation met all requirements HISTORICAL CRITERIA FOR SUCCESSFUL TREATMENT Biomedical sterilizations – FDA

Analysis of suspicious powders following the post 9/11 anthrax scare.

PubMed

Wills, Brandon; Leikin, Jerrold; Rhee, James; Saeedi, Bijan

2008-06-01

Following the 9/11 terrorist attacks, SET Environmental, Inc., a Chicago-based environmental and hazardous materials management company received a large number of suspicious powders for analysis. Samples of powders were submitted to SET for anthrax screening and/or unknown identification (UI). Anthrax screening was performed on-site using a ruggedized analytical pathogen identification device (R.A.P.I.D.) (Idaho Technologies, Salt Lake City, UT). UI was performed at SET headquarters (Wheeling, IL) utilizing a combination of wet chemistry techniques, infrared spectroscopy, and gas chromatography/mass spectroscopy. Turnaround time was approximately 2-3 hours for either anthrax or UI. Between October 10, 2001 and October 11, 2002, 161 samples were analyzed. Of these, 57 were for anthrax screening only, 78 were for anthrax and UI, and 26 were for UI only. Sources of suspicious powders included industries (66%), U.S. Postal Service (19%), law enforcement (9%), and municipalities (7%). There were 0/135 anthrax screens that were positive. There were no positive anthrax screens performed by SET in the Chicago area following the post-9/11 anthrax scare. The only potential biological or chemical warfare agent identified (cyanide) was provided by law enforcement. Rapid anthrax screening and identification of unknown substances at the scene are useful to prevent costly interruption of services and potential referral for medical evaluation.

Multigeneration Cross-Contamination of Mail with Bacillus anthracis Spores

PubMed Central

Edmonds, Jason; Lindquist, H. D. Alan; Sabol, Jonathan; Martinez, Kenneth; Shadomy, Sean; Cymet, Tyler; Emanuel, Peter

2016-01-01

The release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. Previous incidents from Sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of Bacillus anthracis spores as an aerosol or contaminant. Prior studies have demonstrated that Bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demonstrated this ability with Bacillus anthracis spores, which have morphological differences that may affect adhesion properties between spore and formite. In this study, equipment developed to simulate interactions across three generations of envelopes subjected to tumbling and mixing was used to evaluate the potential for cross-contamination of B. anthracis spores in simulated mail handling. In these experiments, we found that the potential for cross-contamination through letter tumbling from one generation to the next varied between generations while the presence of a fluidizer had no statistical impact on the transfer of material. Likewise, the presence or absence of a fluidizer had no statistically significant impact on cross-contamination levels or reaerosolization from letter opening. PMID:27123934

The current state of bioterrorist attack surveillance and preparedness in the US

PubMed Central

Grundmann, Oliver

2014-01-01

The use of biological agents as weapons to disrupt established structures, such as governments and especially larger urban populations, has been prevalent throughout history. Following the anthrax letters sent to various government officials in the fall of 2001, the US has been investing in prevention, surveillance, and preparation for a potential bioterrorism attack. Additional funding authorized since 2002 has assisted the Centers for Disease Control and Prevention, the Department of Health and Human Services, and the Environmental Protection Agency to invest in preventative research measures as well as preparedness programs, such as the Laboratory Response Network, Hospital Preparedness Program, and BioWatch. With both sentinel monitoring systems and epidemiological surveillance programs in place for metropolitan areas, the immediate threat of a large-scale bioterrorist attack may be limited. However, early detection is a crucial factor to initiate immediate response measures to prevent further spread following dissemination of a biological agent. Especially in rural areas, an interagency approach to train health care workers and raise awareness for the general public remain primary tasks, which is an ongoing challenge. Risk-management approaches in responding to dissemination of biological agents, as well as appropriate decontamination measures that reduce the probability of further contamination, have been provided, and suggest further investments in preparedness and surveillance. Ongoing efforts to improve preparedness and response to a bioterrorist attack are crucial to further reduce morbidity, mortality, and economic impact on public health. PMID:25328421

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

ERIC Educational Resources Information Center

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…

Biological and chemical terrorism scenarios and implications for detection systems needs

NASA Astrophysics Data System (ADS)

Gordon, Susanna P.; Chumfong, Isabelle; Edwards, Donna M.; Gleason, Nathaniel J.; West, Todd; Yang, Lynn

2007-04-01

Terrorists intent on causing many deaths and severe disruption to our society could, in theory, cause hundreds to tens of thousands of deaths and significant contamination of key urban facilities by using chemical or biological (CB) agents. The attacks that have occurred to date, such as the 1995 Aum Shinrikyo CB attacks and the 2001 anthrax letters, have been very small on the scale of what is possible. In order to defend against and mitigate the impacts of large-scale terrorist attacks, defensive systems for protection of urban areas and high-value facilities from biological and chemical threats have been deployed. This paper reviews analyses of such scenarios and of the efficacy of potential response options, discusses defensive systems that have been deployed and detectors that are being developed, and finally outlines the detection systems that will be needed for improved CB defense in the future. Sandia's collaboration with San Francisco International Airport on CB defense will also be briefly reviewed, including an overview of airport facility defense guidelines produced in collaboration with Lawrence Berkeley National Laboratory. The analyses that will be discussed were conducted by Sandia National Laboratories' Systems Studies Department in support of the U.S. Department of Homeland Security (DHS) Science and Technology Directorate, and include quantitative analyses utilizing simulation models developed through close collaboration with subject matter experts, such as public health officials in urban areas and biological defense experts.

The Potential Impact of an Anthrax Attack on Real Estate Prices and Foreclosures in Seattle.

PubMed

Dormady, Noah; Szelazek, Thomas; Rose, Adam

2014-01-01

This article provides a methodology for the economic analysis of the potential consequences of a simulated anthrax terrorism attack on real estate within the Seattle metropolitan area. We estimate spatially disaggregated impacts on median sales price of residential housing within the Seattle metro area following an attack on the central business district (CBD). Using a combination of longitudinal panel regression and GIS analysis, we find that the median sales price in the CBD could decline by as much as $280,000, and by nearly $100,000 in nearby communities. These results indicate that total residential property values could decrease by over $50 billion for Seattle, or a 33% overall decline. We combine these estimates with HUD's 2009 American Housing Survey (AHS) to further predict 70,000 foreclosures in Seattle spatial zones following the terrorism event. © 2013 Society for Risk Analysis.

Anthrax vaccination strategies

PubMed Central

Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

2009-01-01

The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

Recent Federal Policies Affecting the Cybersecurity and Resiliency Landscape

DTIC Science & Technology

2014-01-23

Mellon University Homeland Security Act of 2002 Was introduced in the aftermath of • September 11 attacks • mailings of anthrax spores Established...natural disasters, cyber incidents, industrial accidents, pandemics , acts of terrorism, sabotage, and destructive criminal activity targeting critical...August 21, 1963 (NCS) • After September 11 − HSPD 1, 5, 7, 8, 12, 20, 21 − Homeland Security Act of 2002 − PS-PREP • After Mailings of Anthrax

Facilitation of Risk Communication During the Anthrax Attacks of 2001: The Organizational Backstory

PubMed Central

Chess, Caron; Clarke, Lee

2007-01-01

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. PMID:17666692

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

PubMed

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.

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

PubMed

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.

A Bivalent Anthrax-Plague Vaccine That Can Protect against Two Tier-1 Bioterror Pathogens, Bacillus anthracis and Yersinia pestis.

PubMed

Tao, Pan; Mahalingam, Marthandan; Zhu, Jingen; Moayeri, Mahtab; Kirtley, Michelle L; Fitts, Eric C; Andersson, Jourdan A; Lawrence, William S; Leppla, Stephen H; Chopra, Ashok K; Rao, Venigalla B

2017-01-01

Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, Bacillus anthracis and Yersinia pestis , the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from Y. pestis and PA from B. anthracis , in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel ® elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against simultaneous challenge with Y. pestis and the lethal toxin of B. anthracis , demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis . This bivalent anthrax-plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats.

Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

PubMed

Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

2016-12-01

The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

Space Technology to Device that Destroys Pathogens Such As Anthrax

NASA Technical Reports Server (NTRS)

2002-01-01

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

Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.

PubMed

Guarner, Jeannette; Zaki, Sherif R

2006-01-01

From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).

9/11 to the Iraq War: Using Books to Help Children Understand Troubled Times

ERIC Educational Resources Information Center

Rycik, Mary Taylor

2006-01-01

Four years after the 9/11 attack on the United States, the country continues to be in considerable turmoil. Children have lived through the devastation of the September 11th attacks, the panic over the anthrax mailings, the hunt for terrorists in Afghanistan, elevated homeland security threat levels, the war in Iraq, the tsunami disaster, and…

Small molecule inhibitors of anthrax edema factor.

PubMed

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.

Space Technology to Device That Destroys Pathogens Such as Anthrax

NASA Technical Reports Server (NTRS)

2002-01-01

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

Bacillus anthracis

PubMed Central

Spencer, R C

2003-01-01

The events of 11 September 2001 and the subsequent anthrax outbreaks have shown that the West needs to be prepared for an increasing number of terrorist attacks, which may include the use of biological warfare. Bacillus anthracis has long been considered a potential biological warfare agent, and this review will discuss the history of its use as such. It will also cover the biology of this organism and the clinical features of the three disease forms that it can produce: cutaneous, gastrointestinal, and inhalation anthrax. In addition, treatment and vaccination strategies will be reviewed. PMID:12610093

Multigeneration Cross Contamination of Mail with Bacillus Species Spores by Tumbling ▿

PubMed Central

Edmonds, Jason; Clark, Paul; Williams, Leslie; Lindquist, H. D. Alan; Martinez, Kenneth; Gardner, Warren; Shadomy, Sean; Hornsby-Myers, Jennifer

2010-01-01

In 2001, envelopes loaded with Bacillus anthracis spores were mailed to Senators Daschle and Leahy as well as to the New York Post and NBC News buildings. Additional letters may have been mailed to other news agencies because there was confirmed anthrax infection of employees at these locations. These events heightened the awareness of the lack of understanding of the mechanism(s) by which objects contaminated with a biological agent might spread disease. This understanding is crucial for the estimation of the potential for exposure to ensure the appropriate response in the event of future attacks. In this study, equipment to simulate interactions between envelopes and procedures to analyze the spread of spores from a “payload” envelope (i.e., loaded internally with a powdered spore preparation) onto neighboring envelopes were developed. Another process to determine whether an aerosol could be generated by opening contaminated envelopes was developed. Subsequent generations of contaminated envelopes originating from a single payload envelope showed a consistent two-log decrease in the number of spores transferred from one generation to the next. Opening a tertiary contaminated envelope resulted in an aerosol containing 103 B. anthracis spores. We developed a procedure for sampling contaminated letters by a nondestructive method aimed at providing information useful for consequence management while preserving the integrity of objects contaminated during the incident and preserving evidence for law enforcement agencies. PMID:20511424

Emergency response to an anthrax attack

PubMed Central

Wein, Lawrence M.; Craft, David L.; Kaplan, Edward H.

2003-01-01

We developed a mathematical model to compare various emergency responses in the event of an airborne anthrax attack. The system consists of an atmospheric dispersion model, an age-dependent dose–response model, a disease progression model, and a set of spatially distributed two-stage queueing systems consisting of antibiotic distribution and hospital care. Our results underscore the need for the extremely aggressive and timely use of oral antibiotics by all asymptomatics in the exposure region, distributed either preattack or by nonprofessionals postattack, and the creation of surge capacity for supportive hospital care via expanded training of nonemergency care workers at the local level and the use of federal and military resources and nationwide medical volunteers. The use of prioritization (based on disease stage and/or age) at both queues, and the development and deployment of modestly rapid and sensitive biosensors, while helpful, produce only second-order improvements. PMID:12651951

Exposure to Bioterrorism and Mental Health Response among Staff on Capitol Hill

PubMed Central

Pfefferbaum, Betty; Vythilingam, Meena; Martin, Gregory J.; Schorr, John K.; Boudreaux, Angela S.; Spitznagel, Edward L.; Hong, Barry A.

2009-01-01

The October 2001 anthrax attacks heralded a new era of bioterrorism threat in the U.S. At the time, little systematic data on mental health effects were available to guide authorities' response. For this study, which was conducted 7 months after the anthrax attacks, structured diagnostic interviews were conducted with 137 Capitol Hill staff workers, including 56 who had been directly exposed to areas independently determined to have been contaminated. Postdisaster psychopathology was associated with exposure; of those with positive nasal swab tests, PTSD was diagnosed in 27% and any post-anthrax psychiatric disorder in 55%. Fewer than half of those who were prescribed antibiotics completed the entire course, and only one-fourth had flawless antibiotic adherence. Thirty percent of those not exposed believed they had been exposed; 18% of all study participants had symptoms they suspected were symptoms of anthrax infection, and most of them sought medical care. Extrapolation of raw numbers to large future disasters from proportions with incorrect belief in exposure in this limited study indicates a potential for important public health consequences, to the degree that people alter their healthcare behavior based on incorrect exposure beliefs. Incorrect belief in exposure was associated with being very upset, losing trust in health authorities, having concerns about mortality, taking antibiotics, and being male. Those who incorrectly believe they were exposed may warrant concern and potential interventions as well as those exposed. Treatment adherence and maintenance of trust for public health authorities may be areas of special concern, warranting further study to inform authorities in future disasters involving biological, chemical, and radiological agents. PMID:20028246

Determination of serum IgG antibodies to Bacillus anthracis protective antigen in environmental sampling workers using a fluorescent covalent microsphere immunoassay.

PubMed

Biagini, R E; Sammons, D L; Smith, J P; Page, E H; Snawder, J E; Striley, C A F; MacKenzie, B A

2004-08-01

To evaluate potential exposure to Bacillis anthracis (Ba) spores in sampling/decontamination workers in the aftermath of an anthrax terror attack. Fifty six serum samples were obtained from workers involved in environmental sampling for Ba spores at the American Media, Inc. (AMI) building in Boca Raton, FL after the anthrax attack there in October 2001. Nineteen sera were drawn from individuals both pre-entry and several weeks after entrance into the building. Nine sera each were drawn from unique individuals at the pre-entry and follow up blood draws. Thirteen donor control sera were also evaluated. Individuals were surveyed for Ba exposure by measurement of serum Ba anti-protective antigen (PA) specific IgG antibodies using a newly developed fluorescent covalent microsphere immunoassay (FCMIA). Four sera gave positive anti-PA IgG results (defined as anti-PA IgG concentrations > or = the mean microg/ml anti-PA IgG from donor control sera (n = 13 plus 2 SD which were also inhibited > or = 85% when the serum was pre-adsorbed with PA). The positive sera were the pre-entry and follow up samples of two workers who had received their last dose of anthrax vaccine in 2000. It appears that the sampling/decontamination workers of the present study either had insufficient exposure to Ba spores to cause the production of anti-PA IgG antibodies or they were exposed to anthrax spores without producing antibody. The FCMIA appears to be a fast, sensitive, accurate, and precise method for the measurement of anti-PA IgG antibodies.

Bioterrorism and the nervous system.

PubMed

Han, M H; Zunt, J R

2003-11-01

Recent events of war, terrorist attacks, and mail-borne anthrax exposure have produced increasing awareness of potential bioterrorism attacks in the United States and other parts of the world. Physicians and healthcare personnel play a key role in identifying potential bioterrorist attacks. Early recognition and preparedness for bioterrorism-associated illnesses is especially important for neurologists because most bioterrorism agents can directly or indirectly affect the nervous system. This article reviews the neurologic manifestations, diagnosis, and treatments of syndromes caused by potential bioterrorism agents, as well as the potential side effects of vaccines against some of these agents.

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

PubMed

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.

Benefit from NASA

NASA Image and Video Library

2002-02-01

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

Syndrome Surveillance Using Parametric Space-Time Clustering

DOE Office of Scientific and Technical Information (OSTI.GOV)

KOCH, MARK W.; MCKENNA, SEAN A.; BILISOLY, ROGER L.

2002-11-01

As demonstrated by the anthrax attack through the United States mail, people infected by the biological agent itself will give the first indication of a bioterror attack. Thus, a distributed information system that can rapidly and efficiently gather and analyze public health data would aid epidemiologists in detecting and characterizing emerging diseases, including bioterror attacks. We propose using clusters of adverse health events in space and time to detect possible bioterror attacks. Space-time clusters can indicate exposure to infectious diseases or localized exposure to toxins. Most space-time clustering approaches require individual patient data. To protect the patient's privacy, we havemore » extended these approaches to aggregated data and have embedded this extension in a sequential probability ratio test (SPRT) framework. The real-time and sequential nature of health data makes the SPRT an ideal candidate. The result of space-time clustering gives the statistical significance of a cluster at every location in the surveillance area and can be thought of as a ''health-index'' of the people living in this area. As a surrogate to bioterrorism data, we have experimented with two flu data sets. For both databases, we show that space-time clustering can detect a flu epidemic up to 21 to 28 days earlier than a conventional periodic regression technique. We have also tested using simulated anthrax attack data on top of a respiratory illness diagnostic category. Results show we do very well at detecting an attack as early as the second or third day after infected people start becoming severely symptomatic.« less

Benefit from NASA

NASA Image and Video Library

2002-02-01

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

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

PubMed

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

2017-01-01

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

Identification and analysis of obstacles in bioterrorism preparedness and response

NASA Astrophysics Data System (ADS)

Sincavage, Suzanne Michele

The focus of this study was to identify and analyze the obstacles to bioterrorism preparedness and response facing emergency management agencies and public authorities. In order to establish the limits of this discussion, the obstacles will examine a combined conceptual framework of public health, environmental security and social response. The interdisciplinary characteristics of this framework are ideal for addressing the issue of bioterrorism because of its simultaneous impact, which encompasses the complex interrelationships that pertain to public health and national security and social response. Based on a review of literature, the obstacles presented range from the absence of an effective surveillance system for biological terrorism related diseases to the inadequate training of first responders in bioterrorism preparedness and the difficult challenges of a mass casualty situation and the intense pressures associated with the crisis response. Furthermore, the impending reality of bioterrorism will further illustrate a close examination of the characteristics and management of three major biowarfare agents---anthrax, plague and smallpox. Finally, to provide a realistic understanding of the impact of bioterrorism, three case studies of actual events and two hypothetical scenarios will be discussed. Specifically, the discussion will provide the following three unconventional terrorist attacks: the recent anthrax attacks of 2001, the Aum Shinrikyo's attack of the Tokyo subway in 1995, and the Rajneeshees' use of salmonella poisoning in 1994. The inclusion of the hypothetical scenarios of two massive outbreaks of smallpox and anthrax will be presented to illuminate the seriousness and magnitude of the threat of bioterrorism and the probable consequences of failing to overcome the obstacles presented in this study. The importance of this research cannot be overemphasized, the threat is undeniably serious, and the potential for biological agents to cause devastating casualties can be minimized with the fighting strength of education.

Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States.

PubMed Central

Jernigan, J. A.; Stephens, D. S.; Ashford, D. A.; Omenaca, C.; Topiel, M. S.; Galbraith, M.; Tapper, M.; Fisk, T. L.; Zaki, S.; Popovic, T.; Meyer, R. F.; Quinn, C. P.; Harper, S. A.; Fridkin, S. K.; Sejvar, J. J.; Shepard, C. W.; McConnell, M.; Guarner, J.; Shieh, W. J.; Malecki, J. M.; Gerberding, J. L.; Hughes, J. M.; Perkins, B. A.

2001-01-01

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10(3)/mm(3) (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported. PMID:11747719

Science Publishing in the Age of Bioterrorism

ERIC Educational Resources Information Center

Atlas, Ronald

2003-01-01

Following the terrorist attacks of September 11, 2001, and the subsequent anthrax bioterrorism mailings, the science community and others worried that technical articles might inadvertently aid those planning acts of terrorism. Some authors asked the American Society for Microbiology (ASM) for permission to withhold critical information from…

Civil Military Cooperation for Counterterrorism Operations within the United States

DTIC Science & Technology

2013-03-01

as well as the subsequent attempts to contaminate Americans with anthrax , dramatically exposed the nation’s vulnerabilities to domestic terrorism and...terrorism, natural disasters, large-scale cyber-attacks, and pandemics .”23 One of the primary concerns for the U.S. is the dangerous type of weapons that

An Ounce of Prevention is a Ton of Work: Mass Antibiotic Prophylaxis for Anthrax, New York City, 2001

PubMed Central

Moskin, Linda C.; Zucker, Jane R.

2003-01-01

Protocols for mass antibiotic prophylaxis against anthrax were under development in New York City beginning in early 1999. This groundwork allowed the city’s Department of Health to rapidly respond in 2001 to six situations in which cases were identified or anthrax spores were found. The key aspects of planning and lessons learned from each of these mass prophylaxis operations are reviewed. Antibiotic distribution was facilitated by limiting medical histories to issues relevant to prescribing prophylactic antibiotic therapy, formatting medical records to facilitate rapid decision making, and separating each component activity into discrete work stations. Successful implementation of mass prophylaxis operations was characterized by clarity of mission and eligibility criteria, well-defined lines of authority and responsibilities, effective communication, collaboration among city agencies (including law enforcement), and coordination of staffing and supplies. This model can be adapted for future planning needs including possible attacks with other bioterrorism agents, such as smallpox. PMID:12780998

CDC's Evolving Approach to Emergency Response.

PubMed

Redd, Stephen C; Frieden, Thomas R

The Centers for Disease Control and Prevention (CDC) transformed its approach to preparing for and responding to public health emergencies following the anthrax attacks of 2001. The Office of Public Health Preparedness and Response, an organizational home for emergency response at CDC, was established, and 4 programs were created or greatly expanded after the anthrax attacks: (1) an emergency management program, including an Emergency Operations Center; (2) increased support of state and local health department efforts to prepare for emergencies; (3) a greatly enlarged Strategic National Stockpile of medicines, vaccines, and medical equipment; and (4) a regulatory program to assure that work done on the most dangerous pathogens and toxins is done as safely and securely as possible. Following these changes, CDC led responses to 3 major public health emergencies: the 2009-10 H1N1 influenza pandemic, the 2014-16 Ebola epidemic in West Africa, and the ongoing Zika epidemic. This article reviews the programs of CDC's Office of Public Health Preparedness, the major responses, and how these responses have resulted in changes in CDC's approach to responding to public health emergencies.

Theoretical perspectives on public communication preparedness for terrorist attacks.

PubMed

Wray, Ricardo J; Kreuter, Matthew W; Jacobsen, Heather; Clements, Bruce; Evans, R Gregory

2004-01-01

The experience of federal health authorities in responding to the mailed anthrax attacks in the Fall of 2001 sheds light on the challenges of public information dissemination in emergencies. Lessons learned from the Fall of 2001 have guided more recent efforts related to crisis communication and preparedness goals. This article applies theories and evidence from the field of communication to provide an orientation to how public health communication can best contribute to the preparedness effort. This theoretical orientation provides a framework to systematically assess current recommendations for preparedness communication.

DHS HS-STEM Final Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, Anna Christine

2014-09-01

Throughout my HS-STEM internship, I worked on two different projects with a systems analysis group at Sandia National Laboratories in Livermore, California (SNLCA). The first, and primary, project entailed building a conceptual model of health surveillance detection of a bioterror attack. The second project was much smaller in scope and looked at cost tradeoffs between volumetric and surface decontamination after the release of anthrax in a city. Both projects helped me to understand the challenges of planning for a bioterror attack and the importance of preparedness in the public health sector.

Creating a state medical response system for medical disaster management: the North Carolina experience.

PubMed

Kearns, Randy D; Skarote, Mary Beth; Peterson, Jeff; Hubble, Michael W; Winslow, James E

2014-09-01

The purpose of this work was to examine the creation and evolution of the North Carolina state medical response system (SMRS). During the past 30 years, states and local communities have developed a somewhat incongruent patchwork of medical disaster response systems. Several local or regional programs participated in the National Disaster Medical System; however, aside from the Disaster Medical Assistance Teams, most of these local resources lacked national standards and national direction. The September 11, 2001 terrorist attacks in Washington, DC and New York, and the anthrax-laced letters mailed to prominent individuals in the US media and others (bioterrorism) in the months that followed were tragic, but they served as both a tipping point and a unifying factor to drive preparedness activities on a national level. Each state responded to the September 11, 2001 attacks by escalating planning and preparedness efforts for a medical disaster response. The North Carolina SMRS was created based on the overall national direction and was tailored to meet local needs such as hurricane response. This article reviews the accomplishments to date and examines future aims. From regional medical response teams to specialty programs such as ambulance strike teams, burn surge planning, electronic inventory and tracking systems, and mobile pharmacy resources, the North Carolina SMRS has emerged as a national leader. Each regional coalition, working with state leadership, has developed resources and has used those resources while responding to disasters in North Carolina. The program is an example of how national leadership can work with state and local agencies to develop a comprehensive and effective medical disaster response system.

Documentation of Production: Allied Medical Publication 8(B), Volume 2, Medical Planning Guide of NBC Battle Casualties (Biological)

DTIC Science & Technology

2006-06-01

causing Venezuelan Equine Encephalitis (VEE). Dose Range Signs/Symptoms of Illness Category Number (organisms) Typical Description Abbreviation 1...98 Table VIII-8. Number of Infected Personnel after a Venezuelean equine encephalitis (VEE) Attack...tactical scenario, agent (anthrax, botulinum neurotoxin, plague, tularemia, Staphylococcal enterotoxin B, Q fever, Venezuelan Equine Encephalitis

Why It Takes Prevention, Not Detection, to Fight Bioterrorism

ERIC Educational Resources Information Center

Janata, Jiri (Art)

2005-01-01

Following the events which took place on September 11, 2001, and the anthrax attacks which occurred after that date, US authorities became concerned with the idea that an assault with chemical or biological weapons could take place on American territory or in American ships or planes. A worrisome model for such an assault was the 1995 terrorist…

WEAPONS-GRADE ANTHRAX: DETERMINING THE ID-50 (INHALATION) IN RHESUS MONKEYS USING A BIOLOGICALLY-BASED MODEL FOR USE IN HUMAN RISK ASSESSMENT

EPA Science Inventory

One of the significant discoveries following the bioterrorist attacks of October 2001 was that a modified form of Bacillus anthracis (Ames strain) was the causative agent. Physical alteration of the inoculum had occurred; the electrostatic charge had been altered and the resultin...

A Bivalent Anthrax–Plague Vaccine That Can Protect against Two Tier-1 Bioterror Pathogens, Bacillus anthracis and Yersinia pestis

PubMed Central

Tao, Pan; Mahalingam, Marthandan; Zhu, Jingen; Moayeri, Mahtab; Kirtley, Michelle L.; Fitts, Eric C.; Andersson, Jourdan A.; Lawrence, William S.; Leppla, Stephen H.; Chopra, Ashok K.; Rao, Venigalla B.

2017-01-01

Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from Y. pestis and PA from B. anthracis, in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel® elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against simultaneous challenge with Y. pestis and the lethal toxin of B. anthracis, demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent anthrax–plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats. PMID:28694806

Responding to Terror: The Impact of September 11 on K-12 Schools and Schools' Responses

ERIC Educational Resources Information Center

Auger, Richard W.; Seymour, John W.; Roberts, Walter B., Jr.

2004-01-01

The terror attacks on the United States of September 11, 2001, and the anthrax terror campaign that followed had profound implications not only in the political world but also in the realm of professional school counseling. School counselors nationwide were thrust in the position of responding to a traumatic situation on a scale previously…

Straight talk with... Tom Inglesby. Interview by Kevin Jiang.

PubMed

Inglesby, Tom

2013-06-01

When letters containing anthrax spores were mailed to several US senators and media offices in September 2001, just one week after the 9/11 attacks, bioterrorism catapulted to the national stage. Political leaders and public health officials, desperate for guidance on this once-theoretical scenario, turned to experts including Tom Inglesby, then deputy director of the Johns Hopkins Center for Civilian Biodefense Strategies, a bioterrorism research and analysis think tank in Baltimore. In the years that followed, Inglesby and his colleagues ran exercises to simulate bioterror incidents, established a peer-reviewed journal on biodefense and advised government agencies on how to reduce the public health impact of biological threats.Today, he continues his work with the think tank, which moved to the University of Pittsburgh Medical Center (UPMC) in 2003 (although it stayed headquartered in Baltimore) and which was recently renamed the UPMC Center for Health Security. As director and chief executive officer for the past four years, Inglesby has expanded the center's focus toward preventing public health crises arising from infectious diseases, pandemics and major natural disasters, in addition to biological, chemical and nuclear accidents or threats. Inglesby spoke with Kevin Jiang about how responses to bioterrorism, pandemics and natural disasters aren't all that different.

Screening mail for powders using terahertz technology

NASA Astrophysics Data System (ADS)

Kemp, Mike

2011-11-01

Following the 2001 Anthrax letter attacks in the USA, there has been a continuing interest in techniques that can detect or identify so-called 'white powder' concealed in envelopes. Electromagnetic waves (wavelengths 100-500 μm) in the terahertz frequency range penetrate paper and have short enough wavelengths to provide good resolution images; some materials also have spectroscopic signatures in the terahertz region. We report on an experimental study into the use of terahertz imaging and spectroscopy for mail screening. Spectroscopic signatures of target powders were measured and, using a specially designed test rig, a number of imaging methods based on reflection, transmission and scattering were investigated. It was found that, contrary to some previous reports, bacterial spores do not appear to have any strong spectroscopic signatures which would enable them to be identified. Imaging techniques based on reflection imaging and scattering are ineffective in this application, due to the similarities in optical properties between powders of interest and paper. However, transmission imaging using time-of-flight of terahertz pulses was found to be a very simple and sensitive method of detecting small quantities (25 mg) of powder, even in quite thick envelopes. An initial feasibility study indicates that this method could be used as the basis of a practical mail screening system.

A Bayesian method for characterizing distributed micro-releases: II. inference under model uncertainty with short time-series data.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marzouk, Youssef; Fast P.; Kraus, M.

2006-01-01

Terrorist attacks using an aerosolized pathogen preparation have gained credibility as a national security concern after the anthrax attacks of 2001. The ability to characterize such attacks, i.e., to estimate the number of people infected, the time of infection, and the average dose received, is important when planning a medical response. We address this question of characterization by formulating a Bayesian inverse problem predicated on a short time-series of diagnosed patients exhibiting symptoms. To be of relevance to response planning, we limit ourselves to 3-5 days of data. In tests performed with anthrax as the pathogen, we find that thesemore » data are usually sufficient, especially if the model of the outbreak used in the inverse problem is an accurate one. In some cases the scarcity of data may initially support outbreak characterizations at odds with the true one, but with sufficient data the correct inferences are recovered; in other words, the inverse problem posed and its solution methodology are consistent. We also explore the effect of model error-situations for which the model used in the inverse problem is only a partially accurate representation of the outbreak; here, the model predictions and the observations differ by more than a random noise. We find that while there is a consistent discrepancy between the inferred and the true characterizations, they are also close enough to be of relevance when planning a response.« less

Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

PubMed

Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

2013-07-21

There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. Published by Elsevier Ltd.

Capture of Aerosols by Iodinated Fiber Media

DTIC Science & Technology

2004-09-15

fibrous media if provided with 70-80% relative humidity and atmospheric dust (Maus et al., 2000). Spore -forming bacteria such as Bacillus anthracis are...States. The anthrax spores sent out during these attacks were classified as being highly concentrated and processed to be disseminated and inhaled...media, and produce more undesirable bioaerosols. This phenomenon has been reported in many studies in heating, ventilation, and air conditioning ( HVAC

Responding to biological incidents--what are the current issues in remediation of the contaminated environment?

PubMed

Pottage, T; Goode, E; Wyke, S; Bennett, A M

2014-11-01

Since 2000 there have been a number of biological incidents resulting in environmental contamination with Bacillus anthracis, the causative agent of anthrax. These incidents include the US anthrax attacks in 2001, the US and UK drumming incidents in 2006-2008 and more recently, anthrax contamination of heroin in 2009/2010 and 2012/2013. Remediation techniques used to return environments to normal have varied between incidents, with different decontamination technologies being employed. Many factors need to be considered before a remediation strategy or recovery option can be implemented, including; cost, time (length of application), public perception of risk, and sampling strategies (and results) to name a few. These incidents have demonstrated that consolidated guidance for remediating biologically contaminated environments in the aftermath of a biological incident was required. The UK Recovery Handbook for Biological Incidents (UKRHBI) is a project led by Public Health England (PHE), formerly the Health Protection Agency (HPA) to provide guidance and advice on how to remediate the environment following a biological incident or outbreak of infection, and is expected to be published in 2015. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Investigation of an outbreak of cutaneous anthrax in Banlu village, Lianyungang, China, 2012

PubMed Central

Liang-liang, Cui; Li, LI; Ming-lei, Zhang; Fang, Qi; Liang, Ying; Chang-jun, Bao

2012-01-01

Objective After notification of a suspected case of anthrax following the slaughtering of a sick cow in Banlu village, an area that has not had any anthrax cases for decades, we aimed to confirm the outbreak, determine the transmission mechanism and implement control measures. Methods The outbreak response team interviewed all people that had contact with the sick cow. Three types of cases’ specimens were collected and tested by blood smear, real-time polymerase chain reaction (PCR) and the gold colloid method. Traceback of potentially contaminated meat and cattle were conducted. Results There were five confirmed and three probable cases verified among 17 people who had contact with the sick cow – an attack rate of 47%. The incubation period ranged from one to eight days with a median of two days. All eight cases had lesions. All were native residents of Banlu village aged between 21 and 48 years. Five male cases were professional butchers; two females and one male were temporary assistants. The sick cow’s meat and hide, as well as all cattle processed at the same time, were recalled. Hypochlorite was used to disinfect the contaminated environments, butchering facilities and the contacts’ personal effects. Conclusion This outbreak was caused by anthrax bacillus transmitted to contacts from the tissues of the sick cow. Control of the outbreak was managed by recalling all potentially infected meat and disinfecting the slaughter house and the suspected cases’ personal effects and environment. PMID:23908932

The Federal Role in Terrorism Insurance. Evaluating Alternatives in an Uncertain World

DTIC Science & Technology

2007-01-01

representation of RAND intellectual property is provided for non-commercial use only. Unauthorized posting of RAND PDFs to a non-RAND Web site is...Swiss Re Life & Health America Inc. Richard Thomas* Senior vice president Chief underwriting officer American International Group Steven Wechsler ...bomb, outdoor anthrax, nuclear bomb Attack scaling S [0.33, 3.0] Postattack government compensation Market retention R [$27.5 billion, $100 billion

Concerns of Capitol Hill staff workers after bioterrorism: focus group discussions of authorities' response.

PubMed

North, Carol S; Pollio, David E; Pfefferbaum, Betty; Megivern, Deborah; Vythilingam, Meena; Westerhaus, Elizabeth Terry; Martin, Gregory J; Hong, Barry A

2005-08-01

Systematic studies of mental health effects of bioterrorism on exposed populations have not been carried out. Exploratory focus groups were conducted with an exposed population to provide qualitative data and inform empirical research. Five focus groups of 28 political worker volunteers were conducted 3 months after the October 15, 2001, anthrax attack on Capitol Hill. More than 2000 transcribed focus group passages were categorized using qualitative software. The category with the most items was authorities' response (23% passages), and much of this discussion pertained to communication by authorities. The category with the fewest items was symptoms (4%). Identified issues were less within individuals and more between them and authorities. Risk communication by authorities regarding safety and medical issues was a prominent concern among Capitol Hill office staff workers regarding the anthrax incident on Capitol Hill. This suggests focus on risk communication in developing interventions, but more systematic investigation is needed.

United States biodefense, international law, and the problem of intent.

PubMed

Enemark, Christian

2005-01-01

Since the anthrax attacks of 2001 in the United States, annual U.S. government spending on biodefense programs has increased enormously. U.S. biodefense was once exclusively the domain of military agencies and was aimed principally at protecting battlefield troops against the products of state-run biological warfare programs. Today, it is engaged in and promoted by a variety of government agencies contemplating "bioterrorism," and it is aimed principally at protecting the American civilian population. I ask if certain U.S. biodefense policies, pointedly those funding "threat assessment" projects, make biological attacks paradoxically more likely by undermining international and transnational norms against deliberately causing disease. I conclude that they do and consider the ramifications of this answer.

Conflict in the 21st Century: Counterstrategies for the WMD Terrorist

DTIC Science & Technology

1999-04-01

general categories of bio-agents: bacteria , fungi , rickettsiae, chlamydia, viruses , and toxins.18 Anthrax, plague, and tularemia are some of the better...real threat may be a terrorist organization with the will and capability to use a nuclear, chemical, or biological weapon against America’s territory...nervous system .8 These are some of the most lethal substances known to man. Chemical agents are most hazardous when they attack the body passively

Non-State Actors and their Risks to American Society

DTIC Science & Technology

2013-03-01

done in house but out of sight of the broader Japanese community.31 The attack was conducted by dispersing the anthrax spores from an elevated...a spiritual cleansing ritual and that the police could not enter. Since Japanese law protects religious freedom and practices, the police departed...created their weapon system in house and their target was the broader Japanese populace. The Tokyo subway system is among the heaviest used subway

Bioterrorism for the respiratory physician.

PubMed

Waterer, Grant W; Robertson, Hannah

2009-01-01

Terrorist attacks by definition are designed to cause fear and panic. There is no question that a terrorist attack using biological agents would present a grave threat to stability of the society in which they were released. Early recognition of such a bioterrorist attack is crucial to containing the damage they could cause. As many of the most likely bioterrorism agents present with pulmonary disease, respiratory physicians may be crucial in the initial recognition and diagnosis phase, and certainly would be drawn into treatment of affected individuals. This review focuses on the biological agents thought most likely to be used by terrorists that have predominantly respiratory presentations. The primary focus of this review is on anthrax, plague, tularaemia, ricin, and Staphylococcal enterotoxin B. The pathogenesis, clinical manifestations and treatment of these agents will be discussed as well as historical examples of their use. Other potential bioterrorism agents with respiratory manifestations will also be discussed briefly.

Prediction of Aerosol Hazard Arising from the Opening of an Anthrax Letter in an Open Office Environment Using Computational Fluid Dynamics

DTIC Science & Technology

2006-10-01

of BG spores in the Heating, Ventilation, and Air Conditioning ( HVAC ) system; (3) the effect of deposition and re-suspension of BG spores not being... spores re-entering the study area through the HVAC system not being accounted for in the simulation. The time histories of concentration at the...The HVAC system was turned on for about 15 minutes until the flow reaches a pseudo-steady state condition, after which the BG spores were released

Federal and State Quarantine and Isolation Authority

DTIC Science & Technology

2006-08-16

agents that are naturally occurring or released during a terrorist attack, the isolation of infected persons, and the quarantine of certain cities or...http://www.cdc.gov/ncidod/dq/sars_facts/isolationquarantine.pdf]. 9 42 U.S.C. § 264(e) and 42 C.F.R. § 70.2. agent from infecting others.5 The... agents ,” which include “anthrax, ebola, plague, smallpox, tularemia, or other bacterial, fungal, rickettsial, or viral agent , biological toxin, or other

Statistical techniques for the characterization of partially observed epidemics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safta, Cosmin; Ray, Jaideep; Crary, David

Techniques appear promising to construct and integrate automated detect-and-characterize technique for epidemics - Working off biosurveillance data, and provides information on the particular/ongoing outbreak. Potential use - in crisis management and planning, resource allocation - Parameter estimation capability ideal for providing the input parameters into an agent-based model, Index Cases, Time of Infection, infection rate. Non-communicable diseases are easier than communicable ones - Small anthrax can be characterized well with 7-10 days of data, post-detection; plague takes longer, Large attacks are very easy.

Risk-based decision making for staggered bioterrorist attacks : resource allocation and risk reduction in "reload" scenarios.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemaster, Michelle Nicole; Gay, David M.; Ehlen, Mark Andrew

2009-10-01

Staggered bioterrorist attacks with aerosolized pathogens on population centers present a formidable challenge to resource allocation and response planning. The response and planning will commence immediately after the detection of the first attack and with no or little information of the second attack. In this report, we outline a method by which resource allocation may be performed. It involves probabilistic reconstruction of the bioterrorist attack from partial observations of the outbreak, followed by an optimization-under-uncertainty approach to perform resource allocations. We consider both single-site and time-staggered multi-site attacks (i.e., a reload scenario) under conditions when resources (personnel and equipment whichmore » are difficult to gather and transport) are insufficient. Both communicable (plague) and non-communicable diseases (anthrax) are addressed, and we also consider cases when the data, the time-series of people reporting with symptoms, are confounded with a reporting delay. We demonstrate how our approach develops allocations profiles that have the potential to reduce the probability of an extremely adverse outcome in exchange for a more certain, but less adverse outcome. We explore the effect of placing limits on daily allocations. Further, since our method is data-driven, the resource allocation progressively improves as more data becomes available.« less

Terror Medicine as Part of the Medical School Curriculum

PubMed Central

Cole, Leonard A.; Wagner, Katherine; Scott, Sandra; Connell, Nancy D.; Cooper, Arthur; Kennedy, Cheryl Ann; Natal, Brenda; Lamba, Sangeeta

2014-01-01

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, Newark, NJ, USA. The proposed 4-year Rutgers curriculum serves as a model that could assist other medical schools contemplating the inclusion of terror medicine in pre-clerkship and clerkship training. PMID:25309891

Terror medicine as part of the medical school curriculum.

PubMed

Cole, Leonard A; Wagner, Katherine; Scott, Sandra; Connell, Nancy D; Cooper, Arthur; Kennedy, Cheryl Ann; Natal, Brenda; Lamba, Sangeeta

2014-01-01

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, Newark, NJ, USA. The proposed 4-year Rutgers curriculum serves as a model that could assist other medical schools contemplating the inclusion of terror medicine in pre-clerkship and clerkship training.

Negative impact of laws regarding biosecurity and bioterrorism on real diseases.

PubMed

Wurtz, N; Grobusch, M P; Raoult, D

2014-06-01

Research on highly pathogenic microorganisms in biosafety level 3 and 4 laboratories is very important for human public health, as it provides opportunities for the development of vaccines and novel therapeutics as well as diagnostic methods to prevent epidemics. However, in recent years, after the anthrax and World Trade Center attacks in 2001 in the USA, the threat of bioterrorism has grown for both the public and the authorities. As a result, technical and physical containment measures and biosafety and biosecurity practices have been implemented in laboratories handling these dangerous pathogens. Working with selected biological agents and toxins is now highly regulated, owing to their potential to pose a threat to public health and safety, despite the fact that the anthrax attack was found to be the result of a lack of security at a US Army laboratory. Thus, these added regulations have been associated with a large amount of fruitless investment. Herein, we describe the limitations of research in these facilities, and the multiple consequences of the increased regulations. These limitations have seriously negatively impacted on the number of collaborations, the size of research projects, and, more generally, scientific research on microbial pathogens. Clearly, the actual number of known victims and fatalities caused by the intentional use of microorganisms has been negligible as compared with those caused by naturally acquired human infections. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Keeping the Air Clean and Safe: An Anthrax Smoke Detector

NASA Technical Reports Server (NTRS)

2005-01-01

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

Biological weapons and bioterrorism in the first years of the twenty-first century.

PubMed

Leitenberg, Milton

2002-09-01

This paper evaluates four recent developments in biological-weapons politics and bioterrorism. First is American opposition to finalization of a verification protocol for the Biological Weapons Convention; second, a successful attempt at mass-casualty terrorism; third, an ongoing investigation into the bioterrorist capabilities of the al Qaeda network; and, fourth, a series of fatal anthrax attacks in the United States. The first of these evaluations is informed by interviews conducted between 2000 and 2002 with policy principals in the United States and elsewhere.

Logistics modelling: improving resource management and public information strategies in Florida.

PubMed

Walsh, Daniel M; Van Groningen, Chuck; Craig, Brian

2011-10-01

One of the most time-sensitive and logistically-challenging emergency response operations today is to provide mass prophylaxis to every man, woman and child in a community within 48 hours of a bioterrorism attack. To meet this challenge, federal, state and local public health departments in the USA have joined forces to develop, test and execute large-scale bioterrorism response plans. This preparedness and response effort is funded through the US Centers for Disease Control and Prevention's Cities Readiness Initiative, a programme dedicated to providing oral antibiotics to an entire population within 48 hours of a weaponised inhalation anthrax attack. This paper will demonstrate how the State of Florida used a logistics modelling tool to improve its CRI mass prophylaxis plans. Special focus will be on how logistics modelling strengthened Florida's resource management policies and validated its public information strategies.

Anthrax Vaccine and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus in the U.S. Military: A Case-Control Study.

PubMed

Bardenheier, Barbara H; Duffy, Jonathan; Duderstadt, Susan K; Higgs, Jay B; Keith, Michael P; Papadopoulos, Patricia J; Gilliland, William R; McNeil, Michael M

2016-10-01

U.S. military personnel assigned to areas deemed to be at high risk for anthrax attack receive Anthrax Vaccine Adsorbed (AVA). Few cases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been reported in persons who received AVA. Using a matched case-control study design, we assessed the relationship of RA and SLE with AVA vaccination using the Defense Medical Surveillance System. We identified potential cases using International Classification of Diseases, 9th Revision, Clinical Modification codes and confirmed cases with medical record review and rheumatologist adjudication. Using conditional logistic regression, we estimated odds ratios (OR) for AVA exposure during time intervals ranging from 90 to 1,095 days before disease onset. Among 77 RA cases, 13 (17%) had ever received AVA. RA cases were no more likely than controls to have received AVA when looking back 1,095 days (OR: 1.03; 95% confidence interval [CI]: 0.48-2.19) but had greater odds of exposure in the prior 90 days (OR: 3.93; 95% CI: 1.08-14.27). Among the 39 SLE cases, 5 (13%) had ever received AVA; no significant difference in receipt of AVA was found when compared with controls (OR: 0.91; 95% CI: 0.26-3.25). AVA was associated with recent onset RA, but did not increase the risk of developing RA in the long term. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Distributed micro-releases of bioterror pathogens : threat characterizations and epidemiology from uncertain patient observables.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, Michael M.; Marzouk, Youssef M.; Adams, Brian M.

2008-10-01

Terrorist attacks using an aerosolized pathogen preparation have gained credibility as a national security concern since the anthrax attacks of 2001. The ability to characterize the parameters of such attacks, i.e., to estimate the number of people infected, the time of infection, the average dose received, and the rate of disease spread in contemporary American society (for contagious diseases), is important when planning a medical response. For non-contagious diseases, we address the characterization problem by formulating a Bayesian inverse problem predicated on a short time-series of diagnosed patients exhibiting symptoms. To keep the approach relevant for response planning, we limitmore » ourselves to 3.5 days of data. In computational tests performed for anthrax, we usually find these observation windows sufficient, especially if the outbreak model employed in the inverse problem is accurate. For contagious diseases, we formulated a Bayesian inversion technique to infer both pathogenic transmissibility and the social network from outbreak observations, ensuring that the two determinants of spreading are identified separately. We tested this technique on data collected from a 1967 smallpox epidemic in Abakaliki, Nigeria. We inferred, probabilistically, different transmissibilities in the structured Abakaliki population, the social network, and the chain of transmission. Finally, we developed an individual-based epidemic model to realistically simulate the spread of a rare (or eradicated) disease in a modern society. This model incorporates the mixing patterns observed in an (American) urban setting and accepts, as model input, pathogenic transmissibilities estimated from historical outbreaks that may have occurred in socio-economic environments with little resemblance to contemporary society. Techniques were also developed to simulate disease spread on static and sampled network reductions of the dynamic social networks originally in the individual-based model, yielding faster, though approximate, network-based epidemic models. These reduced-order models are useful in scenario analysis for medical response planning, as well as in computationally intensive inverse problems.« less

Bayesian Integrated Microbial Forensics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarman, Kristin H.; Kreuzer-Martin, Helen W.; Wunschel, David S.

2008-06-01

In the aftermath of the 2001 anthrax letters, researchers have been exploring ways to predict the production environment of unknown source microorganisms. Different mass spectral techniques are being developed to characterize components of a microbe’s culture medium including water, carbon and nitrogen sources, metal ions added, and the presence of agar. Individually, each technique has the potential to identify one or two ingredients in a culture medium recipe. However, by integrating data from multiple mass spectral techniques, a more complete characterization is possible. We present a Bayesian statistical approach to integrated microbial forensics and illustrate its application on spores grownmore » in different culture media.« less

Modeling the geographic distribution of Bacillus anthracis, the causative agent of anthrax disease, for the contiguous United States using predictive ecological [corrected] niche modeling.

PubMed

Blackburn, Jason K; McNyset, Kristina M; Curtis, Andrew; Hugh-Jones, Martin E

2007-12-01

The ecology and distribution of Bacillus anthracis is poorly understood despite continued anthrax outbreaks in wildlife and livestock throughout the United States. Little work is available to define the potential environments that may lead to prolonged spore survival and subsequent outbreaks. This study used the genetic algorithm for rule-set prediction modeling system to model the ecological niche for B. anthracis in the contiguous United States using wildlife and livestock outbreaks and several environmental variables. The modeled niche is defined by a narrow range of normalized difference vegetation index, precipitation, and elevation, with the geographic distribution heavily concentrated in a narrow corridor from southwest Texas northward into the Dakotas and Minnesota. Because disease control programs rely on vaccination and carcass disposal, and vaccination in wildlife remains untenable, understanding the distribution of B. anthracis plays an important role in efforts to prevent/eradicate the disease. Likewise, these results potentially aid in differentiating endemic/natural outbreaks from industrial-contamination related outbreaks or bioterrorist attacks.

Anthrax

DTIC Science & Technology

2017-06-30

agricultural nations dependent on animal husbandry. Epidemics of human anthrax are rare. Large outbreaks of cutaneous anthrax occurred during wars in...dissemination of anthrax. Human Anthrax Human anthrax is traced to agricultural , industrial or, rarely, laboratory acquisition. Only two cases of human-to... Agricultural Anthrax In developed countries, contact with infected animals by farmers, butchers, and veterinarians is implicated in ~20% of cutaneous cases

Three eyelid localized cutaneous anthrax cases.

PubMed

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

2014-12-01

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

Cutaneous anthrax (image)

MedlinePlus

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

Neurologists and the threat of bioterrorism.

PubMed

Donaghy, Michael

2006-11-01

Neurologists are most likely to become involved in primarily diagnosing those bioterrorist attacks utilising botulinum toxin. Oral ingestion, or possibly inhalation, are likely routes of delivery. The characteristic descending paralysis starts in the extraocular and bulbar muscles, with associated autonomic features. Repetitive nerve stimulation usually shows an incremental muscle response. Treatment is supportive. The differential diagnosis is from naturally occurring paralysing illnesses such as Guillain-Barré syndrome, myasthenic crisis or diphtheria, from paralysing seafood neurotoxins (tetrodotoxin, saxitoxin), snake envenomation, and from chemical warfare poisoning by organophosphates. Primary neurological infections are less feasible for use as bioweapons. There are theoretical possibilities of Venezuelan equine encephalitis transmission by inhalation and secondary zoonotic transmission cycles sustained by horses and mosquitoes. Severe haemorrhagic meningitis regularly occurs in anthrax, usually in the aftermath of severe systemic disease likely to have been transmitted by spore inhalation. Panic and psychologically determined 'me-too' symptomatology are likely to pose the biggest diagnostic and management burden on neurologists handling bioterrorist attack on an institution or a random civilian population. Indeed civilian panic and disablement of institutional operations are likely to be prominent intentions of any bioterrorist attack.

Planning the bioterrorism response supply chain: learn and live.

PubMed

Brandeau, Margaret L; Hutton, David W; Owens, Douglas K; Bravata, Dena M

2007-01-01

Responses to bioterrorism require rapid procurement and distribution of medical and pharmaceutical supplies, trained personnel, and information. Thus, they present significant logistical challenges. On the basis of a review of the manufacturing and service supply chain literature, the authors identified five supply chain strategies that can potentially increase the speed of response to a bioterrorism attack, reduce inventories, and save money: effective supply chain network design; effective inventory management; postponement of product customization and modularization of component parts; coordination of supply chain stakeholders and appropriate use of incentives; and effective information management. The authors describe how concepts learned from published evaluations of manufacturing and service supply chains, as well as lessons learned from responses to natural disasters, naturally occurring outbreaks, and the 2001 US anthrax attacks, can be applied to design, evaluate, and improve the bioterrorism response supply chain. Such lessons could also be applied to the response supply chains for disease outbreaks and natural and manmade disasters.

Detecting Bioaerosols When Time Is of the Essence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hazi, A

About seven years ago, Livermore researchers received seed funding from the Laboratory Directed Research and Development Program to develop an instrument that counters bioterrorism by providing a rapid early warning system for pathogens, such as anthrax. (See S&TR, January/February 2002, pp. 24-26.) That instrument, the Autonomous Pathogen Detection System (APDS), is now ready for deployment to better protect the public from a bioaerosol attack, and the development team has been honored with a 2004 R&D 100 Award. The lectern-size APDS can be placed in airports, office buildings, performing arts centers, mass transit systems, sporting arenas--anywhere an attack might be launched.more » APDS was designed to get results fast and get them right, without false positives. Biological scientist Richard Langlois, who spearheaded the APDS development effort, explains, ''The system provides results on the spot. Faster results allow a faster emergency response, which in the end means saving lives.''« less

Terrorism-preparedness training for non-clinical hospital workers: tailoring content and presentation to meet workers' needs.

PubMed

Thorne, Craig D; Oliver, Marc; Al-Ibrahim, Mohamed; Gucer, Patricia W; McDiarmid, Melissa A

2004-07-01

Clinicians have been the primary focus of health care worker training in response to the 2001 terrorist and anthrax attacks. However, many nonclinical hospital workers also are critical in providing medical care during any large-scale emergency. We designed a training program, guided by focus groups, to provide them with information to recognize unusual events and to protect themselves. We compared four different training methods: workbook, video, lecture, and a small-group discussion. One hundred and ninety-one workers participated. After the training, they were more confident in their employer's preparedness to respond to a terrorist attack but specific knowledge did not change substantially. Fortunately, the self-directed workbook (the more economical and least disruptive method) was as effective as the other methods. Our experience may be useful to others who are planning terrorism-preparedness training programs.

Decontamination of Anthrax spores in critical infrastructure and critical assets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boucher, Raymond M.; Crown, Kevin K.; Tucker, Mark David

2010-05-01

Decontamination of anthrax spores in critical infrastructure (e.g., subway systems, major airports) and critical assets (e.g., the interior of aircraft) can be challenging because effective decontaminants can damage materials. Current decontamination methods require the use of highly toxic and/or highly corrosive chemical solutions because bacterial spores are very difficult to kill. Bacterial spores such as Bacillus anthracis, the infectious agent of anthrax, are one of the most resistant forms of life and are several orders of magnitude more difficult to kill than their associated vegetative cells. Remediation of facilities and other spaces (e.g., subways, airports, and the interior of aircraft)more » contaminated with anthrax spores currently requires highly toxic and corrosive chemicals such as chlorine dioxide gas, vapor- phase hydrogen peroxide, or high-strength bleach, typically requiring complex deployment methods. We have developed a non-toxic, non-corrosive decontamination method to kill highly resistant bacterial spores in critical infrastructure and critical assets. A chemical solution that triggers the germination process in bacterial spores and causes those spores to rapidly and completely change to much less-resistant vegetative cells that can be easily killed. Vegetative cells are then exposed to mild chemicals (e.g., low concentrations of hydrogen peroxide, quaternary ammonium compounds, alcohols, aldehydes, etc.) or natural elements (e.g., heat, humidity, ultraviolet light, etc.) for complete and rapid kill. Our process employs a novel germination solution consisting of low-cost, non-toxic and non-corrosive chemicals. We are testing both direct surface application and aerosol delivery of the solutions. A key Homeland Security need is to develop the capability to rapidly recover from an attack utilizing biological warfare agents. This project will provide the capability to rapidly and safely decontaminate critical facilities and assets to return them to normal operations as quickly as possible, sparing significant economic damage by re-opening critical facilities more rapidly and safely. Facilities and assets contaminated with Bacillus anthracis (i.e., anthrax) spores can be decontaminated with mild chemicals as compared to the harsh chemicals currently needed. Both the 'germination' solution and the 'kill' solution are constructed of 'off-the-shelf,' inexpensive chemicals. The method can be utilized by directly spraying the solutions onto exposed surfaces or by application of the solutions as aerosols (i.e., small droplets), which can also reach hidden surfaces.« less

Molecular determinants for a cardiovascular collapse in anthrax

PubMed Central

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

2015-01-01

Bacillus anthracis releases two bipartite proteins, lethal toxin and edema factor, that contribute significantly to the progression of anthrax-associated shock. As blocking the anthrax toxins prevents disease, the toxins are considered the main virulence factors of the bacterium. The anthrax bacterium and the anthrax toxins trigger multiorgan failure associated with enhanced vascular permeability, hemorrhage and cardiac dysfunction in animal challenge models. A recent study using mice that either lacked the anthrax toxin receptor in specific cells and corresponding mice expressing the receptor in specific cell types demonstrated that cardiovascular cells are critical for disease mediated by anthrax lethal toxin. These studies are consistent with involvement of the cardiovascular system, and with an increase of cardiac failure markers observed in human anthrax and in animal models using B. anthracis and anthrax toxins. This review discusses the current state of knowledge regarding the pathophysiology of anthrax and tries to provide a mechanistic model and molecular determinants for the circulatory shock in anthrax. PMID:24389148

Heroin-associated anthrax with minimal morbidity.

PubMed

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

2017-03-08

In 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. He subsequently was found to have anthrax. We describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. His full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention. 2017 BMJ Publishing Group Ltd.

A U.S. Biodefense Strategy Primer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulin, D

2009-05-11

The anthrax mailings that followed the attacks of September 11, 2001 highlighted the need for a comprehensive national strategy to prevent, prepare for, respond to, and mitigate the effects of biological attacks. The goal of U.S. biodefense strategy is to reduce the likelihood of a future biological event, improve overall U.S. public health security, and minimize the economic and social disruption of a biological incident. Presidential communications, federal legislation, and executive agency planning documents provide the foundation for this strategy. Central to current U.S. biodefense strategy is the 2004 Homeland Security Presidential Directive (HSPD) 10, Biodefense for the 21st Century,more » which states that ''the United States will use all means necessary to prevent, protect against, and mitigate biological weapons attacks perpetrated against our homeland and our global interests.'' HSPD-10 also sets forth four pillars of U.S. biodefense: {sm_bullet} Threat awareness includes timely, accurate, and relevant intelligence, threat assessment, and the anticipation of future threats. {sm_bullet} Prevention and protection involve continuing and expanding efforts to limit access to agents, technologies, and knowledge to certain groups and countries as well as protecting critical infrastructure from the effects of biological attacks. {sm_bullet} Surveillance and detection provide early warning or recognition of biological attacks to permit a timely response and mitigation of consequences as well as attribution. {sm_bullet} Response and recovery include pre-attack planning and preparedness, capabilities to treat casualties, risk communications, physical control measures, medical countermeasures, and decontamination capabilities.« less

Casting a wider net for countermeasure R&D funding decisions.

PubMed

Klotz, Lynn

2007-12-01

Among potential bioweapons attacks, endemic infectious diseases (that is, those naturally occurring diseases that afflict us every year), and a potential influenza pandemic, how should we apportion funding and resources for basic research and countermeasure development? To address this question, I argue for a "combined risk assessment" that considers bioweapons attacks with natural pandemics and endemic infectious disease. At present, risk assessments for bioweapons attacks are carried out separately from the assessments long carried out for endemic infectious diseases to make public health and medical care decisions. One result of this separation is that funding decisions may be unduly influenced by an overblown fear of a big bioweapons attack and by political whim. The result of the simplified combined risk assessment presented here argues for more funding and resources for endemic infectious disease and for placing biodefense against anthrax and other bioweapons in a place lower in the risk hierarchy. Since the assessment here considers only fatalities to make the point that our priorities are skewed, the conclusions are only a "first word" on the subject, far from the last. Furthermore, the impact of other issues on priorities, such as national and international policy, is not considered. It is a call for a debate on the public stage of the policy and other rationale and the quantitative risk assessment arguments that now place bioweapons attacks at the top of our risk ranking.

Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults

PubMed Central

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

2014-01-01

The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis. PMID:24447897

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

PubMed

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

2014-02-01

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

Known-plaintext attack on a joint transform correlator encrypting system.

PubMed

Barrera, John Fredy; Vargas, Carlos; Tebaldi, Myrian; Torroba, Roberto; Bolognini, Nestor

2010-11-01

We demonstrate in this Letter that a joint transform correlator shows vulnerability to known-plaintext attacks. An unauthorized user, who intercepts both an object and its encrypted version, can obtain the security key code mask. In this contribution, we conduct a hybrid heuristic attack scheme merge to a Gerchberg-Saxton routine to estimate the encrypting key to decode different ciphertexts encrypted with that same key. We also analyze the success of this attack for different pairs of plaintext-ciphertext used to get the encrypting code. We present simulation results for the decrypting procedure to demonstrate the validity of our analysis.

Targeted Silencing of Anthrax Toxin Receptors Protects against Anthrax Toxins*

PubMed Central

Arévalo, Maria T.; Navarro, Ashley; Arico, Chenoa D.; Li, Junwei; Alkhatib, Omar; Chen, Shan; Diaz-Arévalo, Diana; Zeng, Mingtao

2014-01-01

Anthrax spores can be aerosolized and dispersed as a bioweapon. Current postexposure treatments are inadequate at later stages of infection, when high levels of anthrax toxins are present. Anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2). We hypothesized that host cells would be protected from anthrax toxins if anthrax toxin receptor expression was effectively silenced using RNA interference (RNAi) technology. Thus, anthrax toxin receptors in mouse and human macrophages were silenced using targeted siRNAs or blocked with specific antibody prior to challenge with anthrax lethal toxin. Viability assays were used to assess protection in macrophages treated with specific siRNA or antibody as compared with untreated cells. Silencing CMG2 using targeted siRNAs provided almost complete protection against anthrax lethal toxin-induced cytotoxicity and death in murine and human macrophages. The same results were obtained by prebinding cells with specific antibody prior to treatment with anthrax lethal toxin. In addition, TEM8-targeted siRNAs also offered significant protection against lethal toxin in human macrophage-like cells. Furthermore, silencing CMG2, TEM8, or both receptors in combination was also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase activity by edema toxin in human kidney cells. Thus, anthrax toxin receptor-targeted RNAi has the potential to be developed as a life-saving, postexposure therapy against anthrax. PMID:24742682

An overview of anthrax infection including the recently identified form of disease in injection drug users

PubMed Central

Hicks, Caitlin W.; Sweeney, Daniel A.; Cui, Xizhong; Li, Yan

2012-01-01

Purpose Bacillus anthracis infection (anthrax) can be highly lethal. Two recent outbreaks related to contaminated mail in the USA and heroin in the UK and Europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world. Methods This review summarizes the microbiology, pathogenesis, diagnosis, and management of anthrax. Results and conclusions Anthrax, a gram-positive bacterium, has typically been associated with three forms of infection: cutaneous, gastrointestinal, and inhalational. However, the anthrax outbreak among injection drug users has emphasized the importance of what is now considered a fourth disease form (i.e., injectional anthrax) that is characterized by severe soft tissue infection. While cutaneous anthrax is most common, its early stages are distinct and prompt appropriate treatment commonly produces a good outcome. However, early symptoms with the other three disease forms can be nonspecific and mistaken for less lethal conditions. As a result, patients with gastrointestinal, inhalational, or injectional anthrax may have advanced infection at presentation that can be highly lethal. Once anthrax is suspected, the diagnosis can usually be made with gram stain and culture from blood or tissue followed by confirmatory testing (e.g., PCR). While antibiotics are the mainstay of anthrax treatment, use of adjunctive therapies such as anthrax toxin antagonists are a consideration. Prompt surgical therapy appears to be important for successful management of injectional anthrax. PMID:22527064

National Security Letters, the USA PATRIOT Act, and the Constitution: The Tensions between National Security and Civil Rights

ERIC Educational Resources Information Center

Gorham-Oscilowski, Ursula; Jaeger, Paul T.

2008-01-01

In response to the terrorist attacks of 9/11, the USA PATRIOT Act greatly expanded the ability of the Federal Bureau of Investigation to use National Security Letters (NSLs) in investigations and the contexts in which they could be used by relaxing the standards under which NSLs could be employed. NSLs allow investigators to acquire a significant…

Estimating Supplies Program: Evaluation Report

DTIC Science & Technology

2002-12-24

Inhalation, Non-vaccinated1, Incubating, Asymptomatic 352 Anthrax, Inhalation, Non-vaccinated, Prodromal 353 Anthrax, Inhalation, Non-vaccinated, Acute...B-11 PC Code PC Description 354 Anthrax, Inhalation, Vaccinated, Asymptomatic 355 Anthrax, Inhalation, Vaccinated, Prodromal 356...Anthrax, Inhalation, Vaccinated, Acute 357 Plague, Inhalation, Incubating, Asymptomatic 358 Plague, Inhalation, Acute 359 Plague Meningitis 360

Advances in Anthrax Detection: Overview of Bioprobes and Biosensors.

PubMed

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

2015-06-01

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

Holographic deep learning for rapid optical screening of anthrax spores

PubMed Central

Jo, YoungJu; Park, Sangjin; Jung, JaeHwang; Yoon, Jonghee; Joo, Hosung; Kim, Min-hyeok; Kang, Suk-Jo; Choi, Myung Chul; Lee, Sang Yup; Park, YongKeun

2017-01-01

Establishing early warning systems for anthrax attacks is crucial in biodefense. Despite numerous studies for decades, the limited sensitivity of conventional biochemical methods essentially requires preprocessing steps and thus has limitations to be used in realistic settings of biological warfare. We present an optical method for rapid and label-free screening of Bacillus anthracis spores through the synergistic application of holographic microscopy and deep learning. A deep convolutional neural network is designed to classify holographic images of unlabeled living cells. After training, the network outperforms previous techniques in all accuracy measures, achieving single-spore sensitivity and subgenus specificity. The unique “representation learning” capability of deep learning enables direct training from raw images instead of manually extracted features. The method automatically recognizes key biological traits encoded in the images and exploits them as fingerprints. This remarkable learning ability makes the proposed method readily applicable to classifying various single cells in addition to B. anthracis, as demonstrated for the diagnosis of Listeria monocytogenes, without any modification. We believe that our strategy will make holographic microscopy more accessible to medical doctors and biomedical scientists for easy, rapid, and accurate point-of-care diagnosis of pathogens. PMID:28798957

Anthrax blood test

MedlinePlus

Anthrax serology test; Antibody test for anthrax; Serologic test for B. anthracis ... This test may be performed when the health care provider suspects you have anthrax infection. The bacteria that cause ...

Identifying Meningitis During an Anthrax Mass Casualty Incident: Systematic Review of Systemic Anthrax Since 1880

PubMed Central

Katharios-Lanwermeyer, Stefan; Holty, Jon-Erik; Person, Marissa; Sejvar, James; Haberling, Dana; Tubbs, Heather; Meaney-Delman, Dana; Pillai, Satish K.; Hupert, Nathaniel; Bower, William A.; Hendricks, Katherine

2016-01-01

BACKGROUND Bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. Anthrax meningitis may be a manifestation of B. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. Rapid identification and treatment of anthrax meningitis are essential for successful management of an anthrax mass casualty incident. METHODS Three hundred six published reports from 1880 through 2013 met pre-defined inclusion criteria. We calculated descriptive statistics for abstracted cases and conducted multivariable regression on separate derivation and validation cohorts to identify clinical diagnostic and prognostic factors for anthrax meningitis. RESULTS One hundred thirty-two of 363 (36%) cases with systemic anthrax met anthrax meningitis criteria. Severe headache, altered mental status, meningeal signs, and other neurological signs at presentation independently predicted meningitis in the derivation cohort and are proposed as a four-item screening tool for use during mass casualty incidents. Presence of any one factor on admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the absence of any of these signs or symptoms ([LR−]=0.12 [0.19] for adult [pediatric] cohorts), while presence of two or more factors made meningitis very likely ([LR+]=26.5 [29.2]). Survival of anthrax meningitis was predicted by treatment with a bactericidal agent (P=0.005) and use of multiple antimicrobials (P=0.012). CONCLUSIONS We developed an evidence-based triage tool for screening patients for meningitis during an anthrax mass casualty incident; its use could improve both patient outcomes and resource allocation in such an event. PMID:27025833

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

PubMed

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

2015-01-01

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

Identifying Meningitis During an Anthrax Mass Casualty Incident: Systematic Review of Systemic Anthrax Since 1880.

PubMed

Katharios-Lanwermeyer, Stefan; Holty, Jon-Erik; Person, Marissa; Sejvar, James; Haberling, Dana; Tubbs, Heather; Meaney-Delman, Dana; Pillai, Satish K; Hupert, Nathaniel; Bower, William A; Hendricks, Katherine

2016-06-15

Bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. Anthrax meningitis is a common manifestation of B. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. Its rapid identification and treatment are essential for successful management of an anthrax mass casualty incident. Three hundred six published reports from 1880 through 2013 met predefined inclusion criteria. We calculated descriptive statistics for abstracted cases and conducted multivariable regression on separate derivation and validation cohorts to identify clinical diagnostic and prognostic factors for anthrax meningitis. One hundred thirty-two of 363 (36%) cases with systemic anthrax met anthrax meningitis criteria. Severe headache, altered mental status, meningeal signs, and other neurological signs at presentation independently predicted meningitis in the derivation cohort and were tested as a 4-item assessment tool for use during anthrax mass casualty incidents. Presence of any 1 factor on admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the absence of any of these signs or symptoms (likelihood ratio [LR]- = 0.12 [0.19] for adult [pediatric] cohorts), while presence of 2 or more made meningitis very likely (LR+ = 26.5 [30.0]). Survival of anthrax meningitis was predicted by treatment with a bactericidal agent (P = .005) and use of multiple antimicrobials (P = .01). We developed an evidence-based assessment tool for screening patients for meningitis during an anthrax mass casualty incident. Its use could improve both patient outcomes and resource allocation in such an event. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Evaluation of the House Fly Musca domestica as a Mechanical Vector for an Anthrax

PubMed Central

Fasanella, Antonio; Scasciamacchia, Silvia; Garofolo, Giuliano; Giangaspero, Annunziata; Tarsitano, Elvira; Adone, Rosanna

2010-01-01

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. PMID:20808920

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

PubMed

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

2016-01-01

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

Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945–2014 Identified through Systematic Literature Review

PubMed Central

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

2015-01-01

Background Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of two weeks; bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax; and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. Methods To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. Results A total of 149 cases of systemic anthrax were identified (cutaneous [n=59], gastrointestinal [n=28], inhalation [n=26], primary anthrax meningitis [n=19], multiple routes [n=9], and injection [n=8]). Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n=77), survival was greater for those receiving a total of ≥3 antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Conclusion Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident. PMID:26623698

Translations on Eastern Europe, Political, Sociological, and Military Affairs, Number 1335

DTIC Science & Technology

1976-12-21

their colleague was driven out. 8 The "open letter" to the GDR leadership , signed by 12 writers and by sculptor Fritz Cremer , is a seemingly...Dissension (Various sources, various dates).. 11 Havemann Letter to Honecker Conflict Seen Within SED Leadership Attack on State Power GDR Follows...between the intel- lectuals, primarily the writers, and the present party leadership ." West German Editorial Frankfurt/Main FRANKFURTER ALLGEMEINE

Rates and risk factors for human cutaneous anthrax in the country of Georgia: National surveillance data, 2008–2015

PubMed Central

Echeverria, Diana; Zakhashvili, Khatuna; Bautista, Christian; Heyer, Nicholas; Imnadze, Paata; Mitrskhulava, Veriko

2018-01-01

Introduction Anthrax is endemic in the country of Georgia. The most common cutaneous anthrax form accounts for 95% of anthrax cases and often is self-resolving. Humans are infected from processing contaminated animal products, contacting sick animals, or by insect bites. Objective We aimed to describe the burden of human cutaneous anthrax and associated risk factors using the national surveillance data. Methods We extracted all human cutaneous anthrax cases from Electronic Integrated Disease Surveillance System (EIDSS) from 1 January 2008 to 31 December 2015. We conducted descriptive analyses to characterize the number of confirmed, probable and suspected cases by age groups, gender, ethnicity, year and geographic area. Results Out of 911 reported cutaneous anthrax cases, 299 (33%) were rejected. Out of remaining 612 cases, 437 (71%), 172 (28%), and 3 (<0.004%) were classified as confirmed, probable and suspected cases of cutaneous Anthrax, respectively; 467 (76.3%) were male. Georgians accounted for 56% (343/612) of cutaneous anthrax cases. Handling animal products (aOR 4.36, 95% CI 2.61–7.26) and living near pastoralist routes (aOR 2.74, 95%CI 1.57–4.76) were associated with cutaneous anthrax. Conclusions This study provides eight-year trends for cutaneous anthrax in humans in the country of Georgia. A comprehensive explanation for the observed rise and fall of the incidence rates of human cutaneous anthrax in 2008–2015 remains to be clarified but is likely associated with discontinuation of mandatory national livestock vaccination in 2008 coupled with weakened human and animal national health systems which were disrupted after the Soviet Union collapsed. Our analysis identifies living near pastoralist routes, handling animal products and travel to endemic areas within two weeks before the disease onset as risk factors for cutaneous anthrax. The evidence underscores the importance of One Health recommendations to activate anthrax awareness campaigns, supervise the destruction of known anthrax carcasses, record global position system coordinates of sites and disinfect infected soils and introduce a participatory health education tool on anthrax. PMID:29415029

Rates and risk factors for human cutaneous anthrax in the country of Georgia: National surveillance data, 2008-2015.

PubMed

Kasradze, Ana; Echeverria, Diana; Zakhashvili, Khatuna; Bautista, Christian; Heyer, Nicholas; Imnadze, Paata; Mitrskhulava, Veriko

2018-01-01

Anthrax is endemic in the country of Georgia. The most common cutaneous anthrax form accounts for 95% of anthrax cases and often is self-resolving. Humans are infected from processing contaminated animal products, contacting sick animals, or by insect bites. We aimed to describe the burden of human cutaneous anthrax and associated risk factors using the national surveillance data. We extracted all human cutaneous anthrax cases from Electronic Integrated Disease Surveillance System (EIDSS) from 1 January 2008 to 31 December 2015. We conducted descriptive analyses to characterize the number of confirmed, probable and suspected cases by age groups, gender, ethnicity, year and geographic area. Out of 911 reported cutaneous anthrax cases, 299 (33%) were rejected. Out of remaining 612 cases, 437 (71%), 172 (28%), and 3 (<0.004%) were classified as confirmed, probable and suspected cases of cutaneous Anthrax, respectively; 467 (76.3%) were male. Georgians accounted for 56% (343/612) of cutaneous anthrax cases. Handling animal products (aOR 4.36, 95% CI 2.61-7.26) and living near pastoralist routes (aOR 2.74, 95%CI 1.57-4.76) were associated with cutaneous anthrax. This study provides eight-year trends for cutaneous anthrax in humans in the country of Georgia. A comprehensive explanation for the observed rise and fall of the incidence rates of human cutaneous anthrax in 2008-2015 remains to be clarified but is likely associated with discontinuation of mandatory national livestock vaccination in 2008 coupled with weakened human and animal national health systems which were disrupted after the Soviet Union collapsed. Our analysis identifies living near pastoralist routes, handling animal products and travel to endemic areas within two weeks before the disease onset as risk factors for cutaneous anthrax. The evidence underscores the importance of One Health recommendations to activate anthrax awareness campaigns, supervise the destruction of known anthrax carcasses, record global position system coordinates of sites and disinfect infected soils and introduce a participatory health education tool on anthrax.

Anthrax in transit; practical experience and intellectual exchange.

PubMed

Jones, Susan D; Teigen, Philip M

2008-09-01

Focusing on three Anglo-American outbreaks of industrial anthrax, this essay engages the question of how local circumstances influenced the transmission of scientific knowledge in the late nineteenth century. Walpole (Massachusetts), Glasgow, and Bradford (Yorkshire) served as important nodes of transnational investigation into anthrax. Knowledge about the morphology and behavior of Bacillus anthracis changed little while in transit between these nodes, even during complex debates about the nature of bacterial morphology, disease causation, and spontaneous generation. Working independently of their more famous counterparts (Robert Koch and Louis Pasteur), Anglo-American anthrax investigators used visual representations of anthrax bacilli to persuade their peers that a specific, identifiable cause produced all forms of anthrax-malignant pustule (cutaneous anthrax), intestinal anthrax, and woolsorter's disease (pneumonic anthrax). By the late 1870s, this point of view also supported what we would today call an ecological notion of the disease's origins in the interactions of people, animals, and microorganisms in the context of global commerce.

An Aggregate of Four Anthrax Cases during the Dry Summer of 2011 in Epirus, Greece.

PubMed

Gaitanis, Georgios; Lolis, Christos J; Tsartsarakis, Antonios; Kalogeropoulos, Chris; Leveidiotou-Stefanou, Stamatina; Bartzokas, Aristidis; Bassukas, Ioannis D

2016-01-01

Human anthrax is currently a sporadic disease in Europe, without significant regional clustering. To report an unexpected aggregate of anthrax cases and correlate local climatic factors with yearly anthrax admissions. Clinical description of a geographical-temporal anthrax aggregate, correlation of disease admissions with local weather data in the period 2001-2014 and literature reports of anthrax clusters from Europe in the last 20 years. We identified 5 cases, all cutaneous: an unexpected aggregate of 4 cases in mid-summer 2011 (including a probable human-to-human transmission) and a sporadic case in August 2005, all in relatively dry periods (p < 0.05). Remarkably, 3/6 reports of human anthrax aggregates from Europe were observed in Balkan Peninsula countries in the year 2011. In the light of the predicted climatic change, unexpected anthrax aggregates during dry periods in southern Europe underscore the risk of future anthrax re-emergence on this continent. © 2015 S. Karger AG, Basel.

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

PubMed

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

2014-08-01

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

Terrorism and the behavioral sciences.

PubMed

Schouten, Ronald

2010-01-01

Terrorism has existed for millennia and is a phenomenon well-known to many parts of the world. Americans were forced to recognize this phenomenon, and our vulnerability to it, by two sets of events in 2001: the attacks on New York City and Washington, DC, and the anthrax mailings that followed shortly thereafter. Psychiatry, psychology, and other behavioral and social sciences have been looked to for assistance in collecting and analyzing intelligence data, understanding terrorism, and developing strategies to combat terrorism. In addition to reviewing areas in which the behavioral sciences have made contributions in addressing this problem, this article discusses the developing roles for behavioral scientists in this field.

Bioterrorism and its aftermath: dealing individually and organizationally with the emotional reactions to an anthrax attack.

PubMed

Sugden, Brian W; Katchmar, Rosemary

2005-01-01

From September 2001 through April 2004, the United States Postal Service (USPS) dealt, for the first time, with bioterrorism resulting in employee deaths and the closure of a large mail processing plant in Washington, D.C. The Employee Assistance Program (EAP) partnered with the USPS throughout this tumultuous time to meet the multiple and evolving behavioral health needs of the employees and facilitate the employees' emotional preparedness for their return to work at the closed facility. This paper discusses the reactions manifested by the employees during this extended period, as well as the EAP activities in the recovery process.

Houston biosecurity: building a national model.

PubMed Central

Casscells, Ward; Mirhaji, Parsa; Lillibridge, Scott; Madjid, Mohammad

2004-01-01

On September 11, 2001, Al Qaeda terrorists committed an atrocity when they used domestic jetliners to crash into buildings in New York City and Washington, DC, killing thousands of people. In October 2001, another act of savagery occurred, this time using anthrax, not airplanes, to take innocent lives. Each incident demonstrates the vulnerability of an open society, and Americans are left to wonder how such acts can be prevented. Two years later, Al Qaeda operatives are reportedly regrouping, recruiting, and changing their tactics to distribute money and messages to operatives around the world. Many experts believe that terrorist attacks are inevitable. Every city is vulnerable to an attack, and none are fully prepared to handle the residual impact of a biological or chemical attack. A survey conducted by the Cable News Network (CNN) in January 2002, studied 30 major US cities, ranking them based on 6 statistical indices of vulnerability. Thirteen cities were deemed better prepared than Houston, 10 were in a similar state of preparedness, and only 6 were less prepared than Houston. We will discuss the protective measures that have been put in place in Houston, and future steps to take. Other cities can model Houston's experience to develop similar plans nation-wide. PMID:17060983

Protecting America's secrets while maintaining academic freedom.

PubMed

Keel, Brooks A

2004-04-01

The terrorist attacks of September 11, 2001, and the subsequent anthrax mail attacks, have had a profound impact on Americans' personal and professional lives and have sparked an active debate regarding the delicate balance between the need for national security and the pursuit of academic freedom. Although academic freedom can be defined in many ways, there are four primary tenets of freedom in an academic environment: freedom to research, freedom to publish, freedom to teach, and freedom to speak. Each of these tenets has come under attack in the wake of September 11, 2001. In this report the author further defines academic freedom and reflects upon recent events that have had a real or perceived impact on this freedom, including (1) attempts to categorize and restrict some research as "sensitive," (2) implementation of export control laws and select agent regulations, (3) limitations on the publication of research findings, (4) prohibition of certain foreign nationals from collaborating with U.S. researchers and receiving education and training in U.S. colleges and universities, and (5) restraint of faculty free speech. The author offers some suggestions as to how academia might achieve a proper balance between protecting our national security while promoting and maintaining academic freedom.

Houston biosecurity: building a national model.

PubMed

Casscells, Ward; Mirhaji, Parsa; Lillibridge, Scott; Madjid, Mohammad

2004-01-01

On September 11, 2001, Al Qaeda terrorists committed an atrocity when they used domestic jetliners to crash into buildings in New York City and Washington, DC, killing thousands of people. In October 2001, another act of savagery occurred, this time using anthrax, not airplanes, to take innocent lives. Each incident demonstrates the vulnerability of an open society, and Americans are left to wonder how such acts can be prevented. Two years later, Al Qaeda operatives are reportedly regrouping, recruiting, and changing their tactics to distribute money and messages to operatives around the world. Many experts believe that terrorist attacks are inevitable. Every city is vulnerable to an attack, and none are fully prepared to handle the residual impact of a biological or chemical attack. A survey conducted by the Cable News Network (CNN) in January 2002, studied 30 major US cities, ranking them based on 6 statistical indices of vulnerability. Thirteen cities were deemed better prepared than Houston, 10 were in a similar state of preparedness, and only 6 were less prepared than Houston. We will discuss the protective measures that have been put in place in Houston, and future steps to take. Other cities can model Houston's experience to develop similar plans nation-wide.

Ability of physicians to diagnose and manage illness due to category A bioterrorism agents.

PubMed

Cosgrove, Sara E; Perl, Trish M; Song, Xiaoyan; Sisson, Stephen D

2005-09-26

Early recognition of a terrorist attack with biologic agents will rely on physician diagnosis. Physicians' ability to diagnose and care for patients presenting after a bioterror event is unknown. The role of online case-based didactics to measure and improve knowledge in the diagnosis and treatment of these patients is unknown. A multicenter online educational intervention was completed by 631 physicians at 30 internal medicine residency programs in 16 states and Washington, DC, between July 1, 2003, and June 10, 2004. Participants completed a pretest, assessing ability to diagnose and manage potential cases of smallpox, anthrax, botulism, and plague. A didactic module reviewing diagnosis and management of these diseases was then completed, followed by a posttest. Pretest performance measured baseline knowledge. Posttest performance compared with pretest performance measured effectiveness of the educational intervention. Results were compared based on year of training and geographic location of the residency program. Correct diagnoses of diseases due to bioterrorism agents were as follows: smallpox, 50.7%; anthrax, 70.5%; botulism, 49.6%; and plague, 16.3% (average, 46.8%). Correct diagnosis averaged 79.0% after completing the didactic module (P<.001). Correct management of smallpox was 14.6%; anthrax, 17.0%; botulism, 60.2%; and plague, 9.7% (average, 25.4%). Correct management averaged 79.1% after completing the didactic module (P<.001). Performance did not differ based on year of training (P = .54) or geographic location (P = .64). Attending physicians performed better than residents (P<.001). Physician diagnosis and management of diseases caused by bioterrorism agents is poor. An online didactic module may improve diagnosis and management of diseases caused by these agents.

Anthrax: a continuing concern in the era of bioterrorism

PubMed Central

2005-01-01

Anthrax, a potentially fatal infection, is a virulent and highly contagious disease. It is caused by a gram-positive, toxigenic, spore-forming bacillus: Bacillus anthracis. For centuries, anthrax has caused disease in animals and, although uncommonly, in humans throughout the world. Descriptions of this naturally occurring disease begin in antiquity. Anthrax is primarily a disease of herbivores, which are infected by ingestion of spores from the soil. With the advent of modern microbiology, Pasteur developed the first successful anthrax vaccine in 1881. The incidence of the disease has continually decreased since the late 19th century, and animal vaccination programs drastically reduced the animal mortality from the disease. However, anthrax spores continue to be documented in soil samples from throughout the world. Research on anthrax as a biological weapon began more than 80 years ago, and today at least 17 nations are believed to have offensive biological weapons programs that include anthrax. Recent events in the USA have shown how society is affected by both hoax and real threats of anthrax bioweapons. This fourth article in the series on weapons of biowarfare/bioterrorism summarizes the historical background of anthrax as well as clinical and laboratory information useful for bioterrorism preparedness. PMID:16200179

Anthrax: an update

PubMed Central

Kamal, SM; Rashid, AKM M; Bakar, MA; Ahad, MA

2011-01-01

Anthrax is a zoonotic disease caused by Bacillus anthracis. It is potentially fatal and highly contagious disease. Herbivores are the natural host. Human acquire the disease incidentally by contact with infected animal or animal products. In the 18th century an epidemic destroyed approximately half of the sheep in Europe. In 1900 human inhalational anthrax occured sporadically in the United States. In 1979 an outbreak of human anthrax occured in Sverdlovsk of Soviet Union. Anthrax continued to represent a world wide presence. The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene. Human anthrax clinically presents in three forms, i.e. cutaneous, gastrointestinal and inhalational. About 95% of human anthrax is cutaneous and 5% is inhalational. Gastrointestinal anthrax is very rare (less than 1%). Inhalational form is used as a biological warefare agent. Penicillin, ciprofloxacin (and other quinolones), doxicyclin, ampicillin, imipenem, clindamycin, clarithromycin, vancomycin, chloramphenicol, rifampicin are effective antimicrobials. Antimicrobial therapy for 60 days is recommended. Human anthrax vaccine is available. Administration of anti-protective antigen (PA) antibody in combination with ciprofloxacin produced 90%-100% survival. The combination of CPG-adjuvanted anthrax vaccine adsorbed (AVA) plus dalbavancin significantly improved survival. PMID:23569822

Ecological suitability modeling for anthrax in the Kruger National Park, South Africa.

PubMed

Steenkamp, Pieter Johan; van Heerden, Henriette; van Schalkwyk, Ockert Louis

2018-01-01

The spores of the soil-borne bacterium, Bacillus anthracis, which causes anthrax are highly resistant to adverse environmental conditions. Under ideal conditions, anthrax spores can survive for many years in the soil. Anthrax is known to be endemic in the northern part of Kruger National Park (KNP) in South Africa (SA), with occasional epidemics spreading southward. The aim of this study was to identify and map areas that are ecologically suitable for the harboring of B. anthracis spores within the KNP. Anthrax surveillance data and selected environmental variables were used as inputs to the maximum entropy (Maxent) species distribution modeling method. Anthrax positive carcasses from 1988-2011 in KNP (n = 597) and a total of 40 environmental variables were used to predict and evaluate their relative contribution to suitability for anthrax occurrence in KNP. The environmental variables that contributed the most to the occurrence of anthrax were soil type, normalized difference vegetation index (NDVI) and precipitation. Apart from the endemic Pafuri region, several other areas within KNP were classified as ecologically suitable. The outputs of this study could guide future surveillance efforts to focus on predicted suitable areas for anthrax, since the KNP currently uses passive surveillance to detect anthrax outbreaks.

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

PubMed Central

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

2016-01-01

Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-γ in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-γ responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-γ responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens. PMID:27007118

Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine adsorbed) in New Zealand white rabbits.

PubMed

Malkevich, Nina V; Basu, Subhendu; Rudge, Thomas L; Clement, Kristin H; Chakrabarti, Ajoy C; Aimes, Ronald T; Nabors, Gary S; Skiadopoulos, Mario H; Ionin, Boris

2013-11-01

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.

Private and public economic incentives for the control of animal diseases: the case of anthrax in livestock.

PubMed

Ndiva Mongoh, M; Hearne, R; Khaitsa, M L

2008-10-01

This study examined the roles of the public and private sectors as economic components of anthrax control with direct reference to the 2005 anthrax outbreak in livestock in North Dakota. Anthrax is an endemic disease in North Dakota, which often causes disease outbreaks in livestock, leading to economic losses to the livestock industry. The economic incentives and interests behind public and private control of an anthrax outbreak are investigated. Anthrax management is most effective with the participation of public and private firms. As anthrax is an infectious disease, its control also brings positive economic externalities, which are not accounted for in a producer's decision to protect animals. Therefore, public programs designed to control the disease must be implemented. The government can change producer response to anthrax by setting up policies and incentives that encourage their participation. However, these interventions must encourage compliance and not discourage producers from actively taking part in anthrax management. Producers have economy-based interests and personal reasons for controlling anthrax in their farms. The main reason behind government intervention is to provide assurance to the public who consume livestock products. Another reason is to assist producers and veterinarians, and to achieve biosecurity and biosafety objectives. The contribution of each animal healthcare partner in making anthrax management a success in North Dakota is discussed.

Polyvalent Recognition of Biopolymers:The Design of Potent Inhibitors of Anthrax Toxin

NASA Astrophysics Data System (ADS)

Kane, Ravi

2007-03-01

Polyvalency -- the simultaneous binding of multiple ligands on one entity to multiple receptors on another -- is a phenomenon that is ubiquitous in nature. We are using a biomimetic approach, inspired by polyvalency, to design potent inhibitors of anthrax toxin. Since the major symptoms and death from anthrax are due primarily to the action of anthrax toxin, the toxin is a prime target for therapeutic intervention. We describe the design of potent polyvalent anthrax toxin inhibitors, and will discuss the role of pattern matching in polyvalent recognition. Pattern-matched polyvalent inhibitors can neutralize anthrax toxin in vivo, and may enable the successful treatment of anthrax during the later stages of the disease, when antibiotic treatment is ineffective.

Possibilities, intentions and threats: dual use in the life sciences reconsidered.

PubMed

van der Bruggen, Koos

2012-12-01

Due to the terrorist attacks of 9/11 and the anthrax letters of a few weeks later, the concept of dual use has spread widely in the life sciences during the past decade. This article is aimed at a clarification of the dual use concept and its scope of application for the life sciences. Such a clarification would greatly facilitate the work of policymakers seeking to ensure security while avoiding undesirable interventions of government in the conduct of science. The article starts with an overview of the main developments in life sciences in relation to dual use. This is illustrated by discussions on synthetic biology and dual use. The findings lead to a reconsideration of the dual use concept. An area in need of further attention is to what extent threats and intentions should have impact on the definition of dual use. Possible threats are analyzed against the background of the phenomenon of securitization of health care and life sciences: considering these sectors of society in security terms. Some caveats that should be taken into account in a dual use policy are described. An acceptable, adequate and applicable definition of the dual use concept could help researchers, universities, companies and policy makers. Such a definition should build upon, but go beyond, the view developed in the influential Fink-report, which concentrates on the so-called 'experiments of concern', e.g. experiments that enhance the virulence of pathogens (National Research Council of the National Academies 2004) It will be argued that-in addition to these more technical aspects-a definition of dual use should include the aspect of threats and intentions.

Developing a Regional Recovery Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesperance, Ann M.; Olson, Jarrod; Stein, Steven L.

2011-09-01

Abstract A biological attack would present an unprecedented challenge for local, state, and federal agencies; the military; the private sector; and individuals on many fronts ranging from vaccination and treatment to prioritization of cleanup actions to waste disposal. To prepare the Seattle region to recover from a biological attack, the Seattle Urban Area Security Initiative (UASI) partners collaborated with military and federal agencies to develop a Regional Recovery Framework for a Biological Attack in the Seattle Urban Area. The goal was to reduce the time and resources required to recover and restore wide urban areas, military installations, and other criticalmore » infrastructure following a biological incident by providing a coordinated systems approach. Based on discussions in small workshops, tabletop exercises, and interviews with emergency response agency staff, the partners identified concepts of operation for various areas to address critical issues the region will face as recovery progresses. Key to this recovery is the recovery of the economy. Although the Framework is specific to a catastrophic, wide-area biological attack using anthrax, it was designed to be flexible and scalable so it could also serve as the recovery framework for an all-hazards approach. The Framework also served to coalesce policy questions that must be addressed for long-term recovery. These questions cover such areas as safety and health, security, financial management, waste management, legal issues, and economic development.« less

Ante- and postmortem diagnostic techniques for anthrax: rethinking pathogen exposure and the geographic extent of the disease in wildlife.

PubMed

Bagamian, Karoun H; Alexander, Kathleen A; Hadfield, Ted L; Blackburn, Jason K

2013-10-01

Although antemortem approaches in wildlife disease surveillance are common for most zoonoses, they have been used infrequently in anthrax surveillance. Classically, anthrax is considered a disease with extremely high mortality. This is because anthrax outbreaks are often detected ex post facto through wildlife or livestock fatalities or spillover transmission to humans. As a result, the natural prevalence of anthrax infection in animal populations is largely unknown. However, in the past 20 yr, antemortem serologic surveillance in wildlife has indicated that not all species exposed succumb to infection, and anthrax exposure may be more widespread than originally appreciated. These studies brought about a multitude of new questions, many of which can be addressed by increased antemortem serologic surveillance in wildlife populations. To fully understand anthrax transmission dynamics and geographic extent, it is important to identify exposure in wildlife hosts and associated factors and, in turn, understand how these influences may drive environmental reservoir dynamics and concurrent disease risk in livestock and humans. Here we review our current understanding of the serologic response to anthrax among wildlife hosts and serologic diagnostic assays used to augment traditional postmortem anthrax surveillance strategies. We also provide recommendations for the use of serology and sentinel species surveillance approaches in anthrax research and management.

Human anthrax as a re-emerging disease.

PubMed

Doganay, Mehmet; Demiraslan, Hayati

2015-01-01

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

Ecological suitability modeling for anthrax in the Kruger National Park, South Africa

PubMed Central

Steenkamp, Pieter Johan; van Schalkwyk, Ockert Louis

2018-01-01

The spores of the soil-borne bacterium, Bacillus anthracis, which causes anthrax are highly resistant to adverse environmental conditions. Under ideal conditions, anthrax spores can survive for many years in the soil. Anthrax is known to be endemic in the northern part of Kruger National Park (KNP) in South Africa (SA), with occasional epidemics spreading southward. The aim of this study was to identify and map areas that are ecologically suitable for the harboring of B. anthracis spores within the KNP. Anthrax surveillance data and selected environmental variables were used as inputs to the maximum entropy (Maxent) species distribution modeling method. Anthrax positive carcasses from 1988–2011 in KNP (n = 597) and a total of 40 environmental variables were used to predict and evaluate their relative contribution to suitability for anthrax occurrence in KNP. The environmental variables that contributed the most to the occurrence of anthrax were soil type, normalized difference vegetation index (NDVI) and precipitation. Apart from the endemic Pafuri region, several other areas within KNP were classified as ecologically suitable. The outputs of this study could guide future surveillance efforts to focus on predicted suitable areas for anthrax, since the KNP currently uses passive surveillance to detect anthrax outbreaks. PMID:29377918

Anthrax Infection

PubMed Central

Sweeney, Daniel A.; Hicks, Caitlin W.; Cui, Xizhong; Li, Yan

2011-01-01

Bacillus anthracis infection is rare in developed countries. However, recent outbreaks in the United States and Europe and the potential use of the bacteria for bioterrorism have focused interest on it. Furthermore, although anthrax was known to typically occur as one of three syndromes related to entry site of (i.e., cutaneous, gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection in injectional drug users is emerging. Although shock has been described with cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5 of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based in part on case series, the estimated mortalities of cutaneous, gastrointestinal, inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively. Nonspecific early symptomatology makes initial identification of anthrax cases difficult. Clues to anthrax infection include history of exposure to herbivore animal products, heroin use, or clustering of patients with similar respiratory symptoms concerning for a bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with Gram stain and culture from blood or surgical specimens followed by confirmatory testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies such as anthrax toxin antagonists is a consideration. PMID:21852539

The danger of lime use in agricultural anthrax disinfection procedures: The potential role of calcium in the preservation of anthrax spores

PubMed Central

Himsworth, Chelsea G.

2008-01-01

Previously, lime (calcium oxide) was recommended by the Canadian Food Inspection Agency (CFIA) as an anthrax disinfectant. However, a recent scientific review of the subject has found evidence to suggest that exposure of anthrax spores to calcium may aid in their survival and viability. For this reason, the CFIA no longer recommends the use of lime for agricultural anthrax disinfection. PMID:19252713

Anthrax: A Guide for Biology Teachers.

ERIC Educational Resources Information Center

Simon, Eric J.

2002-01-01

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

Enhancing Surveillance and Diagnostics in Anthrax-Endemic Countries

PubMed Central

Salzer, Johanna S.; Traxler, Rita M.; Hendricks, Katherine A.; Kadzik, Melissa E.; Marston, Chung K.; Kolton, Cari B.; Stoddard, Robyn A.; Hoffmaster, Alex R.; Bower, William A.; Walke, Henry T.

2017-01-01

Naturally occurring anthrax disproportionately affects the health and economic welfare of poor, rural communities in anthrax-endemic countries. However, many of these countries have limited anthrax prevention and control programs. Effective prevention of anthrax outbreaks among humans is accomplished through routine livestock vaccination programs and prompt response to animal outbreaks. The Centers for Disease Control and Prevention uses a 2-phase framework when providing technical assistance to partners in anthrax-endemic countries. The first phase assesses and identifies areas for improvement in existing human and animal surveillance, laboratory diagnostics, and outbreak response. The second phase provides steps to implement improvements to these areas. We describe examples of implementing this framework in anthrax-endemic countries. These activities are at varying stages of completion; however, the public health impact of these initiatives has been encouraging. The anthrax framework can be extended to other zoonotic diseases to build on these efforts, improve human and animal health, and enhance global health security. PMID:29155651

Recent progress in the development of anthrax vaccines.

PubMed

Kaur, Manpreet; Bhatnagar, Rakesh

2011-12-01

Bacillus anthracis is the etiological agent of anthrax. Although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. The potential use of B. anthracis spores as biowarfare agent has led to immense attention. Prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. This highlights the need for alternative anthrax countermeasures. A number of approaches are being investigated to substitute or supplement the existing anthrax vaccines. These relied on expression of Protective antigen (PA), the key protective immunogen; in bacterial or plant systems; or utilization of attenuated strains of B. anthracis for immunization. Few studies have established potential of domain IV of PA for immunization. Other targets including the spore, capsule, S-layer and anthrax toxin components have been investigated for imparting protective immunity. It has been shown that co-immunization of PA with domain I of lethal factor that binds PA resulted in higher antibody responses. Of the epitope based vaccines, the loop neutralizing determinant, in particular; elicited robust neutralizing antibody response and conferred 97% protection upon challenge. DNA vaccination resulted in varying degree of protection and seems a promising approach. Additionally, the applicability of monoclonal and therapeutic antibodies in the treatment of anthrax has also been demonstrated. The recent progress in the direction of anthrax prophylaxis has been evaluated in this review.

9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Anthrax Spore Vaccine-Nonencapsulated... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore Vaccine.... All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed...

9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Anthrax Spore Vaccine-Nonencapsulated... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore Vaccine.... All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Vaccine To Protect Children From Anthrax--Public.... SUMMARY: The National Biodefense Science Board's (NBSB) Anthrax Vaccine (AV) Working Group (WG) will hold a public engagement workshop on July 7, 2011, to discuss vaccine to protect children from anthrax...

9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Anthrax Spore Vaccine-Nonencapsulated... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore Vaccine.... All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed...

9 CFR 113.66 - Anthrax Spore Vaccine-Nonencapsulated.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Anthrax Spore Vaccine-Nonencapsulated... REQUIREMENTS Live Bacterial Vaccines § 113.66 Anthrax Spore Vaccine—Nonencapsulated. Anthrax Spore Vaccine.... All serials of vaccine shall be prepared from the first through the fifth passage from the Master Seed...

Investigation of inhalation anthrax case, United States.

PubMed

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

2014-02-01

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

When You Visit Your Doctor After a Heart Attack

MedlinePlus

... products will be searched. Shopping Cart Description Qty Price The Harvard Medical School 6-Week Plan for ... Memory: Understanding Age-Related Memory Loss (PDF - Lowest Price!) $18.00 Harvard Health Letter (Print & Online Access ( ...

Public Understanding of Medical Countermeasures.

PubMed

Liu, Brooke Fisher; Quinn, Sandra C; Egnoto, Michael; Freimuth, Vicki; Boonchaisri, Natalie

Medical countermeasures, including new drugs and vaccines, are necessary to protect the public's health from novel diseases and terrorist threats. Experience with the 2001 anthrax attack and the 2009 H1N1 pandemic suggest that there is limited willingness to accept such drugs and that minority groups may respond differently from others. We conducted 148 intercept interviews in the metropolitan Washington, DC, area, examining 2 hypothetical scenarios: a new respiratory virus and public exposure to high levels of radiation. Findings provide insights into key factors that affect whether diverse members of the public comply with recommended protective actions like taking emergency authorized vaccines. These insights can help improve how public health practitioners communicate during uncertain times.

Biosurveillance: A Review and Update

PubMed Central

Kman, Nicholas E.; Bachmann, Daniel J.

2012-01-01

Since the terrorist attacks and anthrax release in 2001, almost $32 billion has been allocated to biodefense and biosurveillance in the USA alone. Surveillance in health care refers to the continual systematic collection, analysis, interpretation, and dissemination of data. When attempting to detect agents of bioterrorism, surveillance can occur in several ways. Syndromic surveillance occurs by monitoring clinical manifestations of certain illnesses. Laboratory surveillance occurs by looking for certain markers or laboratory data, and environmental surveillance is the process by which the ambient air or environment is continually sampled for the presence of biological agents. This paper focuses on the ways by which we detect bioterrorism agents and the effectiveness of these systems. PMID:22242207

Public Understanding of Medical Countermeasures

PubMed Central

Quinn, Sandra C.; Egnoto, Michael; Freimuth, Vicki; Boonchaisri, Natalie

2017-01-01

Medical countermeasures, including new drugs and vaccines, are necessary to protect the public's health from novel diseases and terrorist threats. Experience with the 2001 anthrax attack and the 2009 H1N1 pandemic suggest that there is limited willingness to accept such drugs and that minority groups may respond differently from others. We conducted 148 intercept interviews in the metropolitan Washington, DC, area, examining 2 hypothetical scenarios: a new respiratory virus and public exposure to high levels of radiation. Findings provide insights into key factors that affect whether diverse members of the public comply with recommended protective actions like taking emergency authorized vaccines. These insights can help improve how public health practitioners communicate during uncertain times. PMID:28388223

Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

PubMed

Karadas, S; Aslan, M; Ceylan, M R; Sunnetcioglu, M; Bozan, N; Kara, H; Demir, H

2017-07-01

Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

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

PubMed

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

2016-02-25

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

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

PubMed

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

PubMed Central

Allegye-Cudjoe, Emmanuel; Polkuu, Paul Nokuma; Frimpong, Joseph Asamoah; Nyarko, Kofi Mensah; Bower, William A.; Traxler, Rita

2017-01-01

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. PMID:29028799

Vaccines for preventing anthrax.

PubMed

Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L

2009-04-15

Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. To evaluate the effectiveness, immunogenicity, and safety of vaccines for preventing anthrax. We searched the following databases (November 2008): Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; LILACS; and mRCT. We also searched reference lists. We included randomized controlled trials (RCTs) of individuals and cluster-RCTs comparing anthrax vaccine with placebo, other (non-anthrax) vaccines, or no intervention; or comparing administration routes or treatment regimens of anthrax vaccine. Two authors independently considered trial eligibility, assessed risk of bias, and extracted data. We presented cases of anthrax and seroconversion rates using risk ratios (RR) and 95% confidence intervals (CI). We summarized immunoglobulin G (IgG) concentrations using geometric means. We carried out a sensitivity analysis to investigate the effect of clustering on the results from one cluster-RCT. No meta-analysis was undertaken. One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose response relationship for the anti-protective antigen IgG antibody titre. Intramuscular administration was associated with fewer injection site reactions than subcutaneous injection, and injection site reaction rates were lower when the dosage interval was longer. One cluster-RCT provides limited evidence that a live-attenuated vaccine is effective in preventing cutaneous anthrax. Vaccines based on anthrax antigens are immunogenic in most vaccinees with few adverse events or reactions. Ongoing randomized controlled trials are investigating the immunogenicity and safety of anthrax vaccines.

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Livestock affected with anthrax... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways. (a) Any livestock found on ante-mortem inspection to be affected with anthrax shall be identified...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Livestock affected with anthrax... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways. (a) Any livestock found on ante-mortem inspection to be affected with anthrax shall be identified...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Livestock affected with anthrax... INSPECTION § 309.7 Livestock affected with anthrax; cleaning and disinfection of infected livestock pens and driveways. (a) Any livestock found on ante-mortem inspection to be affected with anthrax shall be identified...

Preparing Houston: lessons learned, future directions

NASA Astrophysics Data System (ADS)

Madjid, Mohammad; Mirhaji, Parsa; Lillibridge, Scott R.; Casscells, S. W.

2003-09-01

On September 11, 2001, Al Qaeda terrorists committed a savage act against humanity when they used domestic jetliners to crash into buildings in New York City and Washington, DC, killing thousands of people. In October 2001, coming on the heels of this savagery was another act of barbarity, this time using anthrax, not jetliners, to take innocent lives. Each incident demonstrates the vulnerability of an open society, and Americans are left to wonder how such acts can be prevented. Now, Al Qaeda operatives are reportedly regrouping, recruiting, and changing their tactics to distribute money and messages to operatives around the world. Many experts believe that terrorist attacks are inevitable. No city is immune from attack, and no city is fully prepared to handle the residual impact of a potentially ravaging biological or chemical attack. A survey conducted by the Cable News Network (CNN) in January 2002, studied 30 major US cities, ranking them based on 6 statistical indices of vulnerability. Thirteen cities were deemed better prepared than Houston, 10 were in a similar state of preparedness, and only 6 were less prepared than Houston. Here, we discuss the measures which have taken place in Houston to make it a safer place and which plans are needed for future. Houston experience can be used as a model to develop similar plans for other cities nation-wide.

Detecting invisible bacillus spores on surfaces using a portable surface-enhanced Raman analyzer

NASA Astrophysics Data System (ADS)

Farquharson, Stuart; Inscore, Frank; Sperry, Jay F.

2006-10-01

Since the distribution of anthrax causing spores through the U.S. Postal System in the autumn of 2001, numerous methods have been developed to detect spores with the goal of minimizing casualties. During and following an attack it is also important to detect spores on surfaces, to assess extent of an attack, to quantify risk of infection by contact, as well as to evaluate post-attack clean-up. To perform useful measurements, analyzers and/or methods must be capable of detecting as few as 10 spores/cm2, in under 5-minutes, with little or no sample preparation or false-positive responses, using a portable device. In an effort to develop such a device, we have been investigating the ability of surfaceenhanced Raman spectroscopy (SERS) to detect dipicolinic acid (DPA) as a chemical signature of bacilli spores. In 2003 we employed SERS to measure DPA extracted from a 10,000 spores per μL sample using hot dodecylamine. Although the entire measurement was performed in 2 minutes, the need to heat the dodecylamine limits field portability of the method. Here we describe the use of a room temperature digesting agent in combination with SERS to detect 220 spores collected from a surface in a 1 μL sample within 3 minutes.

Counterfactual attack on counterfactual quantum key distribution

NASA Astrophysics Data System (ADS)

Zhang, Sheng; Wnang, Jian; Tang, Chao Jing

2012-05-01

It is interesting that counterfactual quantum cryptography protocols allow two remotely separated parties to share a secret key without transmitting any signal particles. Generally, these protocols, expected to provide security advantages, base their security on a translated no-cloning theorem. Therefore, they potentially exhibit unconditional security in theory. In this letter, we propose a new Trojan horse attack, by which an eavesdropper Eve can gain full information about the key without being noticed, to real implementations of a counterfactual quantum cryptography system. Most importantly, the presented attack is available even if the system has negligible imperfections. Therefore, it shows that the present realization of counterfactual quantum key distribution is vulnerable.

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

PubMed Central

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

2016-01-01

Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2−) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R. PMID:26927174

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

PubMed Central

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

2013-01-01

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

Anthrax

MedlinePlus

... made 22 sick. Anthrax is rare. It affects animals such as cattle, sheep, and goats more often ... People can get anthrax from contact with infected animals, wool, meat, or hides. It can cause three ...

Anthrax toxin-induced rupture of artificial lipid bilayer membranes

NASA Astrophysics Data System (ADS)

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

2013-08-01

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

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

NASA Astrophysics Data System (ADS)

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.

Lessons for Control of Heroin-Associated Anthrax in Europe from 2009–2010 Outbreak Case Studies, London, UK

PubMed Central

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

2014-01-01

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009–2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012–13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community. PMID:24959910

Periocular cutaneous anthrax in Jimma Zone, Southwest Ethiopia: a case series

PubMed Central

2013-01-01

Background Anthrax is a zoonotic disease caused by Bacillus anthracis. Naturally occurring human infection is rare and is generally the result of contact with anthrax-infected animals or animal products. Case presentation We examined three patients who had contact with presumed anthrax-infected animal and/or its product and presented with preseptal cellulitis with a localized itchy erythematous papule of the eyelid and non-pitting periorbital edema, followed by ulceration and dark eschar formation. All the three patients responded to intravenous antibiotics, and the lesion resolved leaving scars which caused cicatricial ectropion in all cases. Conclusion Anthrax is a rare disease but should be considered in the differential diagnosis of ulcerative (and eschar forming) preseptal cellulitis with a history of contact with anthrax-infected animals or animal products. Furthermore, cicatrization of the eyelids, one of the sequelae of periocular cutaneous anthrax, should be addressed. Urgent case report to the local zoonotic disease and infection control body and other responsible authorities is recommended. PMID:23924443

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

PubMed

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

2014-07-01

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

Anthrax Basics

MedlinePlus

... with anthrax? Domestic and wild animals such as cattle, sheep, goats, antelope, and deer can become infected ... in wild and domestic grazing animals such as cattle or deer. Anthrax is more common in developing ...

Anthrax: Symptoms

MedlinePlus

... and cause severe illness and even death. Cutaneous anthrax symptoms can include: A group of small blisters ... on the face, neck, arms, or hands Inhalation anthrax symptoms can include: Fever and chills Chest Discomfort ...

MODIFICATION OF ANTHRAX BY IONIZING RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berdjis, C.C.; Gochenour, W.S. Jr.; Henderson, J.E.

1963-11-01

Since dogs are not susceptible to anthrax when inoculated cutaneously, the possible effect of irradiation on susceptibility was explored. Beagles received x irradiation combined with anthrax either simultaneously or three days after irradiation. The controls were irradiated or infected with anthrax alone. A single dose of 125, 250, or 325 r total-body 1-Mev x irradiation was used, which was either equall to or less than the LD/sub 50/ for dogs. A dose rate of 68 r/min in air was used. The distal 1/3 of the femur and the tibia of both hind legs of some dogs in the 250-r groupmore » were shielded from radiation. Spores of Bacillus anthracis which had been heat-shocked 48 hr earlier were injected in two doses (5 x 10/sup 4/ or 1 x 10/sup 6/ spores) by the subcutaneous route into the right axilla either simultaneously with or three days after irradiation. Regardless of dose, anthrax alone did not kill dogs. Irradiation alone killed three of six animals in the 250-r group, two of two in the 325-r group, and none in the 125-r group. The dogs died with the acute radiation syndrome characterized by severe lymphohematopoietic depletion and multiple visceral hemorrhages or manifestations of a hemorrhage diathesis. Lymphopenia was observed. Shielding of hind legs protected the irradiated animals from death. Anthrax combined with irradiation killed most of the dogs, inoculated with either high or low doses of anthrax, between 6 and 12 days after infection regardless of dose and time of irradiation. Shielding of the hind legs of irradiated anthrax- infected dogs did not fully protect the dogs from death; four of seven animals in this group died. In contradistinction to the controls, irradiated anthrax- infected dogs invariably developed septicemia with concomitant diffuse and massive cellulitis and a peculiar histopathologic reaction. The histopathologic reaction was essentially hemorrhagic, poor in inflammatory cells, and exceptionally rich in bacilli and bacterial thrombi. This reaction was not observed in other species injected with anthrax. Thus, the normal resistance of the dog to anthrax was markedly reduced by irradiation. Irradiation may increase the harmful effect of anthrax by disturbing the mechanism of defense in this resistant host. This is probably due to damage to the lymphatic and hematopoietic systems by irradiation, further complicated by the infection. Therefore, this combination seems to create a favorable medium for anthrax spores to germinate and multiply. It seemed to stimulate the germination with rapid dissemination and overwhelming septicemia. This was confirmed by the fact that no bacteremia nor significant, persistent cellulitis was observed in the dogs infected with anthrax alone, while irradiated anthrax-infected dogs died with massive, overwhelming septicemia and extensive cellulitis. (BBB)« less

Anthrax toxin-induced rupture of artificial lipid bilayer membranes

PubMed Central

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

2013-01-01

We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm. PMID:23947891

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

PubMed

Sitali, Doreen Chilolo; Mumba, Chisoni; Skjerve, Eystein; Mweemba, Oliver; Kabonesa, Consolata; Mwinyi, Mwinyi Omary; Nyakarahuka, Luke; Muma, John Bwalya

2017-05-01

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 cold chain facilities decentralized in order to improve accessibility to anthrax vaccine. It is also important to involve the affected communities and collaborate with other disciplines in order to effectively tackle poverty, improve veterinary services and address inherent meat consumption practices within the communities.

Anthrax outbreaks in the humans - livestock and wildlife interface areas of Northern Tanzania: a retrospective record review 2006-2016.

PubMed

Mwakapeje, Elibariki Reuben; Høgset, Sol; Fyumagwa, Robert; Nonga, Hezron Emmanuel; Mdegela, Robinson Hammerthon; Skjerve, Eystein

2018-01-05

Anthrax outbreaks in Tanzania have been reported from the human, livestock and wildlife sectors over several years, and is among the notifiable diseases. Despite frequent anthrax outbreaks, there is no comprehensive dataset indicating the magnitude and distribution of the disease in susceptible species. This study is a retrospective review of anthrax outbreaks from the human, livestock, and wildlife surveillance systems from 2006 to 2016. The objectives were to identify hotspot districts, describe anthrax epidemiology in the hotspot areas, evaluate the efficiency of the anthrax response systems and identify potential areas for further observational studies. We prepared a spreadsheet template for a retrospective comprehensive record review at different surveillance levels in Tanzania. We captured data elements including demographic characteristics of different species, the name of health facility, and date of anthrax diagnosis. Also, we collected data on the date of specimen collection, species screened, type of laboratory test, laboratory results and the outcome recorded at the end of treatment in humans. After establishing the database, we produced maps in Quantum GIS software and transferred cleaned data to Stata software for supportive statistical analysis. Anthrax reported incidences over 4 years in humans were much higher in the Arusha region (7.88/100,000) followed by Kilimanjaro region (6.64/100,000) than other regions of Tanzania Mainland. The health facility based review from hotspot districts in parts of Arusha and Kilimanjaro regions from 2006 to 2016, identified 330 human anthrax cases from the selected health facilities in the two regions. Out of 161 livestock and 57 wildlife specimen tested, 103 and 18 respectively, were positive for anthrax. This study revealed that there is gross under-reporting in the existing surveillance systems which is an obstacle for estimating a true burden of anthrax in the hotspot districts. Repeated occurrences of anthrax in livestock, wildlife and humans in the same locations at the same time calls for the need to strengthen links and promote inter-disciplinary and multi-sectoral collaboration to enhance prevention and control measures under a One Health approach.

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

PubMed Central

Mumba, Chisoni; Skjerve, Eystein; Mweemba, Oliver; Kabonesa, Consolata; Mwinyi, Mwinyi Omary; Nyakarahuka, Luke; Muma, John Bwalya

2017-01-01

Background 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. Methods 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. Results 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. Conclusions Health education campaigns must be intensified to reduce the risk of human exposure. Veterinary extension services should be strengthened and cold chain facilities decentralized in order to improve accessibility to anthrax vaccine. It is also important to involve the affected communities and collaborate with other disciplines in order to effectively tackle poverty, improve veterinary services and address inherent meat consumption practices within the communities. PMID:28498841

A case report of inhalation anthrax acquired naturally.

PubMed

Azarkar, Zohreh; Bidaki, Majid Zare

2016-03-03

Anthrax is a zoonotic occupational disease caused by Bacillus anthracis, a rod-shaped immobile aerobic gram-positive bacteria with spore. Anthrax occurs in humans randomly and with low frequency. Most cases of anthrax are acquired through contact with infected animals or contaminated animal products. This old disease became particularly important since 2001 that the biological spores were exploited in America. Depending on the transmission method of the disease, clinical manifestations occur in three classes: Cutaneous, respiratory, and gastrointestinal anthrax. The respiratory form is considered as the most fatal and a rare form of anthrax intending to show complicated and unusual manifestations. In this case report a rare case of inhalation anthrax acquired naturally in southeast of Iran is presented. A blind 65-year-old man, living in a rural area, was admitted with respiratory infection, fever, dyspnea, loss of appetite, and myalgia. The patient was treated with outpatient antibiotics a week ago. After admission, the patient was again treated for pneumonia, but there was no improvement despite treatment and the patient was suffering from septicemia symptoms. Radiographic images showed wide mediastinum. Bacillus anthracis was isolated from blood and sputum culture and the results were confirmed by colony morphology, biochemical reactions and PCR. The treatment was changed to ciprofloxacin, clindamycin, and penicillin. On the second day of anthrax treatment, the patient was complicated with jaundice, elevation of liver enzymes, and a significant drop in hemoglobin, hematocrit, and platelet despite lack of obvious bleeding and was complicated with respiratory distress and sepsis and died a week after treatment. We could discover no specific exposure associated with anthrax infection for this patient. However, due to being located in an endemic and enzootic area, it is proposed that the exposure occurred through contact with infected airborne dust or an unknown contaminated item. Despite many advances in preventing anthrax, still some rare cases of respiratory and complicated anthrax are emerging. With regard to the threat of bioterrorism, medical staff's sensitivity to the clinical syndrome, methods of prophylaxis and treatment of anthrax must be raised. Fast diagnosis and successful treatment the lethal cases of this infection are of utmost important.

Risk factors associated with anthrax outbreak in animals in North Dakota, 2005: a retrospective case-control study.

PubMed

Mongoh, Mafany Ndiva; Dyer, Neil W; Stoltenow, Charles L; Khaitsa, Margaret L

2008-01-01

We identified the risk factors associated with the anthrax outbreak Of 2005 in animals in North Dakota. Medical records of the 2005 anthrax outbreak were obtained from the Veterinary Diagnostic Laboratory at North Dakota State University. Additional data were obtained from the North Dakota state veterinarian's office, and supplemental questionnaires were administered to producers. The data obtained included ecological and environmental factors, animal health factors, and management factors. Anthrax occurred from July 1 to October 12, 2005. The cases were located in eastern North Dakota around the Red River Basin. Ransom, LaMoure, and Barnes counties reported most cases (71%). Species affected included cattle, bison, horses, sheep, elk, deer, pigs, and llamas. The predominant symptom was sudden death (38%) followed by bleeding from orifices (17%). Chi-square analysis indicated significant differences between case and control premises on the following variables: death reported on neighboring pasture, vaccination period, dry conditions, wet conditions, antibiotic use, multiple vaccination, and type of predator (coyote). Factors that significantly (p<0.05) predicted anthrax occurrences on the final logistic regression model were vaccination, use of antibiotics during an outbreak, and period of vaccine administration (before or during the outbreak). The characteristics of the anthrax outbreak regarding time and place of occurrence, animals affected, clinical signs reported, and mortality rate were consistent with previous reports of natural anthrax outbreaks in animals. A number of factors that significantly predicted anthrax occurrence in animals in the 2005 outbreak in North Dakota were identified. This information is important in planning appropriate control and prevention measures for anthrax, including recommending the right vaccination and treatment regimens in managing future anthrax outbreaks.

Mapping the Distribution of Anthrax in Mainland China, 2005-2013.

PubMed

Chen, Wan-Jun; Lai, Sheng-Jie; Yang, Yang; Liu, Kun; Li, Xin-Lou; Yao, Hong-Wu; Li, Yu; Zhou, Hang; Wang, Li-Ping; Mu, Di; Yin, Wen-Wu; Fang, Li-Qun; Yu, Hong-Jie; Cao, Wu-Chun

2016-04-01

Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood. Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30-49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0-2 months. A boosted regression trees (BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level. Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections.

Mapping the Distribution of Anthrax in Mainland China, 2005–2013

PubMed Central

Yang, Yang; Liu, Kun; Li, Xin-Lou; Yao, Hong-Wu; Li, Yu; Zhou, Hang; Wang, Li-Ping; Mu, Di; Yin, Wen-Wu; Fang, Li-Qun; Yu, Hong-Jie; Cao, Wu-Chun

2016-01-01

Background Anthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood. Methodology/Principal Findings Using the national surveillance data of human and livestock anthrax from 2005 to 2013, we conducted a retrospective epidemiological study and risk assessment of anthrax in mainland China. The potential determinants for the temporal and spatial distributions of human anthrax were also explored. We found that the majority of human anthrax cases were located in six provinces in western and northeastern China, and five clustering areas with higher incidences were identified. The disease mostly peaked in July or August, and males aged 30–49 years had higher incidence than other subgroups. Monthly incidence of human anthrax was positively correlated with monthly average temperature, relative humidity and monthly accumulative rainfall with lags of 0–2 months. A boosted regression trees (BRT) model at the county level reveals that densities of cattle, sheep and human, coverage of meadow, coverage of typical grassland, elevation, coverage of topsoil with pH > 6.1, concentration of organic carbon in topsoil, and the meteorological factors have contributed substantially to the spatial distribution of the disease. The model-predicted probability of occurrence of human cases in mainland China was mapped at the county level. Conclusions/Significance Anthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections. PMID:27097318

Laboratories Face Crackdown in Wake of Anthrax Scare.

ERIC Educational Resources Information Center

Southwick, Ron

2001-01-01

Explores the after-effects on college laboratories of the anthrax mail scare; scientists say the anthrax scare justifies tougher rules on biological agents, but some fear that Congress may go too far. (EV)

Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine.

PubMed

Chabot, Donald J; Ribot, Wilson J; Joyce, Joseph; Cook, James; Hepler, Robert; Nahas, Debbie; Chua, Jennifer; Friedlander, Arthur M

2016-07-25

The efficacy of currently licensed anthrax vaccines is largely attributable to a single Bacillus anthracis immunogen, protective antigen. To broaden protection against possible strains resistant to protective antigen-based vaccines, we previously developed a vaccine in which the anthrax polyglutamic acid capsule was covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B and demonstrated that two doses of 2.5μg of this vaccine conferred partial protection of rhesus macaques against inhalational anthrax . Here, we demonstrate complete protection of rhesus macaques against inhalational anthrax with a higher 50μg dose of the same capsule conjugate vaccine. These results indicate that B. anthracis capsule is a highly effective vaccine component that should be considered for incorporation in future generation anthrax vaccines. Published by Elsevier Ltd.

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

PubMed Central

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

2017-01-01

Anthrax, 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. PMID:28115677

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

PubMed

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.

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

DTIC Science & Technology

2001-04-01

HEALTH RISK COMMUNICATION IN THE ANTHRAX VACCINE IMMUNIZATION PROGRAM: Lessons for the Future Colonel Bradley D. Freeman April 2001 AEPI-IFP-0901...REPORT TYPE AND DATES COVERED Strategy Research Project 4. TITLE AND SUBTITLE Health Risk Communication in the Anthrax Vaccine Immunization Program...Maximum 200 words) When Secretary of Defense William Cohen announced that all military service members would be vaccinated with the anthrax vaccine , few

Presentation of peptides from Bacillus anthracis protective antigen on Tobacco Mosaic Virus as an epitope targeted anthrax vaccine.

PubMed

McComb, Ryan C; Ho, Chi-Lee; Bradley, Kenneth A; Grill, Laurence K; Martchenko, Mikhail

2015-11-27

The current anthrax vaccine requires improvements for rapidly invoking longer-lasting neutralizing antibody responses with fewer doses from a well-defined formulation. Designing antigens that target neutralizing antibody epitopes of anthrax protective antigen, a component of anthrax toxin, may offer a solution for achieving a vaccine that can induce strong and long lasting antibody responses with fewer boosters. Here we report implementation of a strategy for developing epitope focused virus nanoparticle vaccines against anthrax by using immunogenic virus particles to present peptides derived from anthrax toxin previously identified in (1) neutralizing antibody epitope mapping studies, (2) toxin crystal structure analyses to identify functional regions, and (3) toxin mutational analyses. We successfully expressed two of three peptide epitopes from anthrax toxin that, in previous reports, bound antibodies that were partially neutralizing against toxin activity, discovered cross-reactivity between vaccine constructs and toxin specific antibodies raised in goats against native toxin and showed that antibodies induced by our vaccine constructs also cross-react with native toxin. While protection against intoxication in cellular and animal studies were not as effective as in previous studies, partial toxin neutralization was observed in animals, demonstrating the feasibility of using plant-virus nanoparticles as a platform for epitope defined anthrax vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Agroterrorism: the risks to the United States food supply and national security.

PubMed

Gill, Kevin M

2015-01-01

Agroterrorism is a collective term that describes an intentional criminal attack against crops or mankind using viral, bacterial, fungal, or insect-borne agents. Agroterrorism also includes attacks against animals using infectious pathogens such as Burkholderia mallei (glanders), Bacillus anthracis (anthrax), viral avian influenza, foot and mouth disease, and several equine encephalitis viruses. Agents that could be used against crops include the causative agents of wheat blast, rice blast, rice brown spot disease, and wheat stem rust. The primary goal of terrorists using agroterrorism is to spread fear and cause massive economic loss. Subsequent goals include causing disease and death to humans and animals. The use of bioterrorism agents is a much more practical approach than using explosives, for example, to achieve those results since many of these biological agents are commonly found naturally in the environment and are difficult to detect with modern technology. The effective use of biological warfare dates back centuries and can still can be employed by terrorist groups, lone wolves, and political and religious groups to cause death and mayhem on a grand scale.

Measurement of 100 B. anthracis Ames spores within 15 minutes by SERS at the US Army Edgewood Chemical Biological Ctr.

NASA Astrophysics Data System (ADS)

Farquharson, Stuart; Shende, Chetan; Smith, Wayne; Huang, Hermes; Sperry, Jay; Sickler, Todd; Prugh, Amber; Guicheteau, Jason

2014-05-01

Since the distribution of Bacillus anthracis-Ames spores through the US Postal System, there has been a persistent fear that biological warfare agents will be used by terrorists against our military abroad and our civilians at home. While there has been substantial effort since the anthrax attack of 2001 to develop analyzers to detect this and other biological warfare agents, the analyzers remain either too slow, lack sensitivity, produce high false-positive rates, or cannot be fielded. In an effort to overcome these limitations we have been developing a surface-enhanced Raman spectroscopy system. Here we describe the use of silver nanoparticles functionalized with a short peptide to selectively capture Bacillus anthracis spores and produce SER scattering. Specifically, measurements of 100 B. anthracis-Ames spores/mL in ~25 minutes performed at the US Army's Edgewood Chemical Biological Center are presented. The measurements provide a basis for the development of systems that can detect spores collected from the air or water supplies with the potential of saving lives during a biological warfare attack.

Bacillus anthracis (image)

MedlinePlus

... aerobic spore-forming bacterium that causes disease in humans and animals. The bacteria is found in two forms: cutaneous anthrax and inhalation anthrax. Cutaneous anthrax is an infection of the skin caused by direct contact with the bacterium. Inhalation ...

Development of a simple and rapid method for the specific identification of organism causing anthrax by slide latex agglutination.

PubMed

Sumithra, T G; Chaturvedi, V K; Gupta, P K; Sunita, S C; Rai, A K; Kutty, M V H; Laxmi, U; Murugan, M S

2014-05-01

A specific latex agglutination test (LAT) based on anti-PA (protective antigen) antibodies having detection limit of 5 × 10(4) formalin treated Bacillus anthracis cells or 110 ng of PA was optimized in this study. The optimized LAT could detect anthrax toxin in whole blood as well as in serum from the animal models of anthrax infection. The protocol is a simple and promising method for the specific detection of bacteria causing anthrax under routine laboratory, as well as in field, conditions without any special equipments or expertise. The article presents the first report of a latex agglutination test for the specific identification of the cultures of bacteria causing anthrax. As the test is targeting one of anthrax toxic protein (PA), this can also be used to determine virulence of suspected organisms. At the same time, the same LAT can be used directly on whole blood or sera samples under field conditions for the specific diagnosis of anthrax. © 2013 The Society for Applied Microbiology.

Anthrax: A disease of biowarfare and public health importance

PubMed Central

Goel, Ajay Kumar

2015-01-01

Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce and exhibit widespread fear and panic than the actual potential of physical damage. Bacillus anthracis (B. anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non-motile bacterium. This is supposed to be one of the most potent BW agents because its spores are extremely resistant to natural conditions and can survive for several decades in the environment. B. anthracis spores enter the body through skin lesion (cutaneous anthrax), lungs (pulmonary anthrax), or gastrointestinal route (gastrointestinal anthrax) and germinate, giving rise to the vegetative form. Anthrax is a concern of public health also in many countries where agriculture is the main source of income including India. Anthrax has been associated with human history for a very long time and regained its popularity after Sept 2001 incidence in United States. The present review article describes the history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon. PMID:25610847

New Developments in Vaccines, Inhibitors of Anthrax Toxins, and Antibiotic Therapeutics for Bacillus anthracis

PubMed Central

Beierlein, J.M.; Anderson, A.C.

2013-01-01

Bacillus anthracis, the causative agent responsible for anthrax infections, poses a significant biodefense threat. There is a high mortality rate associated with untreated anthrax infections; specifically, inhalation anthrax is a particularly virulent form of infection with mortality rates close to 100%, even with aggressive treatment. Currently, a vaccine is not available to the general public and few antibiotics have been approved by the FDA for the treatment of inhalation anthrax. With the threat of natural or engineered bacterial resistance to antibiotics and the limited population for whom the current drugs are approved, there is a clear need for more effective treatments against this deadly infection. A comprehensive review of current research in drug discovery is presented in this article, including efforts to improve the purity and stability of vaccines, design inhibitors targeting the anthrax toxins, and identify inhibitors of novel enzyme targets. High resolution structural information for the anthrax toxins and several essential metabolic enzymes has played a significant role in aiding the structure-based design of potent and selective antibiotics. PMID:22050756

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

PubMed

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

2015-01-01

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

Coding ethical behaviour: the challenges of biological weapons.

PubMed

Rappert, Brian

2003-10-01

Since 11 September 2001 and the anthrax attacks that followed in the US, public and policy concerns about the security threats posed by biological weapons have increased significantly. With this has come an expansion of those activities in civil society deemed as potential sites for applying security controls. This paper examines the assumptions and implications of national and international efforts in one such area: how a balance or integration can take place between security and openness in civilian biomedical research through devising professional codes of conduct for scientists. Future attempts to establish such codes must find a way of reconciling or at least addressing dilemmatic and tension-ridden issues about the appropriateness of research; a topic that raises fundamental questions about the position of science within society.

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

DTIC Science & Technology

2004-12-15

278 • JID 2005:191 (15 January) • Mikszta et al. M A J O R A R T I C L E Protective Immunization against Inhalational Anthrax: A Comparison of...provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combi- nations described here have the potential to...have produced documented fatali- ties, the fatality rate of inhalational anthrax is nearly 100% without antibiotic intervention. Inhalational an

An adenovirus-vectored nasal vaccine confers rapid and sustained protection against anthrax in a single-dose regimen.

PubMed

Zhang, Jianfeng; Jex, Edward; Feng, Tsungwei; Sivko, Gloria S; Baillie, Leslie W; Goldman, Stanley; Van Kampen, Kent R; Tang, De-chu C

2013-01-01

Bacillus anthracis is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B. anthracis protective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity. The potency of the vaccine was greatly enhanced when codons of the antigen gene were optimized to match the tRNA pool found in human cells. In addition, an adenovirus vector encoding lethal factor can confer partial protection against inhalation anthrax and might be coadministered with a protective antigen-based vaccine.

An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen

PubMed Central

Jex, Edward; Feng, Tsungwei; Sivko, Gloria S.; Baillie, Leslie W.; Goldman, Stanley; Van Kampen, Kent R.; Tang, De-chu C.

2013-01-01

Bacillus anthracis is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B. anthracis protective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity. The potency of the vaccine was greatly enhanced when codons of the antigen gene were optimized to match the tRNA pool found in human cells. In addition, an adenovirus vector encoding lethal factor can confer partial protection against inhalation anthrax and might be coadministered with a protective antigen-based vaccine. PMID:23100479

Anthrax Outbreaks in Bangladesh, 2009–2010

PubMed Central

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

2012-01-01

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

Non-canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development.

PubMed

Liu, Katherine; Wong, Elaine W; Schutzer, Steven E; Connell, Nancy D; Upadhyay, Alok; Bryan, Margarette; Rameshwar, Pranela

2009-08-01

Anthrax receptor (ATR) shares similarities with molecules relevant to haematopoiesis. This suggests that anthrax proteins might bind to these mimicking molecules and exert non-specific haematopoietic effects. The haematopoietic system is the site of immune cell development in the adult. As such, ATR ligand, protective antigen (PA) and the other anthrax proteins, lethal factor, edema factor, could be significant to haematopoietic responses against Bacillus anthracis infection. Because haematopoiesis is the process of immune cell development, effects by anthrax proteins could be relevant to vaccine development. Here, we report on effects of anthrax proteins and toxins on early and late haematopoiesis. Flow cytometry shows binding of PA to haematopoietic cells. This binding might be partly specific because flow cytometry and Western blots demonstrate the presence of ATR1 on haematopoietic cell subsets and the supporting stromal cells. Functional studies with long-term initiating cell and clonogenic assays determined haematopoietic suppression by anthrax toxins and stimulation by monomeric proteins. The suppressive effects were not attributed to cell death, but partly through the induction of haematopoietic suppressors, interleukin (IL)-10 and CCL3 (MIP-1alpha). In summary, anthrax proteins affect immune cell development by effects on haematopoiesis. The type of effect, stimulation or suppression, depend on whether the stimulator is a toxin or monomeric protein. The studies show effects of anthrax proteins beginning at the early stage of haematopoiesis, and also show secondary mediators such as IL-10 and CCL3. The roles of other cytokines and additional ATR are yet to be investigated.

Cutaneous anthrax in Southeast Anatolia of Turkey.

PubMed

Tekin, Recep; Sula, Bilal; Devecı, Ozcan; Tekin, Alicem; Bozkurt, Fatma; Ucmak, Derya; Kaya, Şafak; Bekcibasi, Muhammed; Erkan, Mehmet Emin; Ayaz, Celal; Hosoglu, Salih

2015-03-01

Anthrax is a rare disease cause by Bacillus anthracis, a Gram-positive, rod-shaped endospore-forming capsuled bacterium. Anthrax is manifest in three primary forms: cutaneous, respiratory, and gastrointestinal. Cutaneous anthrax accounts for approximately 95% of all cases of anthrax in humans. In the present study, we evaluated the clinical diagnosis and treatment of cutaneous anthrax, a rare disease that nonetheless remains a serious healthcare problem in developing countries. The complete medical records of patients diagnosed with cutaneous anthrax between January 2001 and December 2012 were examined in a retrospective manner. Cutaneous anthrax was diagnosed by the identification of typical anthrax lesions and/or the presence of Gram-positive-capsuled bacillus after staining with Gram stain and methylen blue in pathology samples obtained from these lesions and the presence of characteristic scarring with a history of severe swelling, black eschar, and positive response to treatment form the basis of diagnosis in cases where cultures were negative for the presence of bacillus. A total of 58 patients were admitted to the hospital with cutaneous anthrax between January 2001 and December 2012. This included 32 (55.2%) males and 26 (44.8%) females, with an age range of 15-82 years and a mean age of 38 ± 13.8 years. The incubation period for the infection ranged between 1 and 20 d (mean 3.7 ± 1.4 d). The most common symptoms at the time of hospital referral were swelling, redness, and black eschar of the skin. The most common lesion site was the hand and fingers (41.3%). Isolated of bacteria was used to diagnose the disease in six cases (23.8%), detection of Gram-positive bacillus in samples of characteristic lesion material was used in seven (28.5%) cases, and the presence of a characteristic lesion was the sole diagnostic criteria in 45 (77.6%) cases. Treatment consisted of penicillin G (12 cases), ampicillin-sulbactam (30 cases), Cefazolin (12 cases), or ciprofloxacin (4 cases). Although the prevalence of anthrax is a decreasing worldwide, it remains a significant problem in developing countries. Rapid identification of the signs and symptoms of cutaneous anthrax is essential for effective treatment. Early supportive treatment and appropriate antimicrobial measures are necessary to address this potentially life-threatening disease.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mostafa, Salwa; Lee, Ida; Islam, Syed K

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/more » L.« less

Cutaneous anthrax in an unusual location: case report.

PubMed

Sari, Tugba; Koruk, Suda Tekin

2015-12-01

Cutaneous anthrax is well known, unlike anthrax of the lumbar region, which is not reported elsewhere. We present a case of anthrax of the lumbar region in a 50-year-old man. The infection was characterised by a wide, black eschar and oedema on an erythematous ground. After isolation of the Gram-positive bacilli from the skin lesions, prompt antibiotic treatment (intravenous sulbactam-ampicillin 1.5 g every six hours) was initiated. Following eradication of the bacilli after 14 days of antibiotic treatment, a split-thickness skin graft was applied. A diagnosis of anthrax depends on clinical suspicion. Early diagnosis, antibiotic and surgical treatment can facilitate the treatment and prevent development of complications.

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

PubMed

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.

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

DTIC Science & Technology

2012-06-28

York City anthrax investigation working group. (2003). Isolated case of bioterrorism-related inhalational anthrax, New York City , 2001. Emerg. Infect...ORIGINAL RESEARCH ARTICLE published: 28 June 2012 doi: 10.3389/fcimb.2012.00087 Inhalational anthrax(Ames aerosol) in naïve and vaccinated New ...Inhalation Antrax (Ames aerosol) In Naive and Vaccinated New Zealand Rabbits: Characterizing The Spread Of Bacteria From Lung Deposition To Bacteremia

The Anthrax Vaccine Debate: A Medical Review for Commanders

DTIC Science & Technology

2001-04-01

tested , certified, and released the new lots for distribution.65 BioPort has a total of 32 lots of Anthrax Vaccine, Adsorbed in storage for ...cit., 1744. 159. New anthrax vaccines have been developed and are ready for clinical testing . But so far, lack of funding has prevented the ...anthrax vaccine. The FDA has not yet certified the new facilities and has not released new lots for sale. DoD has not used any of these

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

PubMed

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

2014-01-01

Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

Barro, Alassane S.; Fegan, Mark; Moloney, Barbara; Porter, Kelly; Muller, Janine; Warner, Simone; Blackburn, Jason K.

2016-01-01

The ecology and distribution of B. anthracis in Australia is not well understood, despite the continued occurrence of anthrax outbreaks in the eastern states of the country. Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extending from southeast Queensland through the centre of New South Wales and into northern Victoria. This definition of the anthrax belt does not consider the role of environmental conditions in the distribution of B. anthracis. Here, we used the genetic algorithm for rule-set prediction model system (GARP), historical anthrax outbreaks and environmental data to model the ecological niche of B. anthracis and predict its potential geographic distribution in Australia. Our models reveal the niche of B. anthracis in Australia is characterized by a narrow range of ecological conditions concentrated in two disjunct corridors. The most dominant corridor, used to redefine a new anthrax belt, parallels the Eastern Highlands and runs from north Victoria to central east Queensland through the centre of New South Wales. This study has redefined the anthrax belt in eastern Australia and provides insights about the ecological factors that limit the distribution of B. anthracis at the continental scale for Australia. The geographic distributions identified can help inform anthrax surveillance strategies by public and veterinary health agencies. PMID:27280981

Phylogenetic Characteristics of Anthrax Outbreaks in Liaoning Province, China, 2001-2015.

PubMed

Mao, Lingling; Zhang, Enmin; Wang, Zijiang; Li, Yan; Zhou, Hang; Liu, Xuesheng; Zhang, Huijuan; Cai, Hong; Liang, Xudong; Sun, Yingwei; Zhang, Zhikai; Li, Wei; Yao, Wenqing; Wei, Jianchun

2016-01-01

Anthrax is a continuous threat in China, especially in rural regions. In July 2015, an anthrax outbreak occurred in Xifeng County, Liaoning Province. A total of 10 cutaneous anthrax cases were reported, with 210 people under medical observation. In this study, the general characteristics of human anthrax outbreak occurred in Liaoning Province were described, and all cases were caused by butchering and contacting sick animal. Meanwhile, the phylogenetic relationship between outbreak-related isolates/samples of the year 2015 and previous Bacillus anthracis strains was analyzed by means of canonical single nucleotide polymorphisms (canSNP), multiple-locus variable-number tandem repeat analysis (MLVA) with 15 markers and single-nucleotide repeats (SNR) analysis. There are two canSNP subgroups found in Liaoning, A.Br.001/002 and A.Br.Ames, and a total of six MLVA 15 genotypes and five SNR genotypes were observed. The strain collected from anthrax outbreak in Xifeng County in 2015 was classified as A.Br.001/002 subgroup and identified as MLVA15-29 genotype, with same SNR profile (CL10: 17, CL12: 15, CL33: 29, and CL35: 13). So we conclude that the same clone of B.anthracis caused the anthrax outbreak in Xifeng County in 2015, and this clone is different to previous isolates. Strengthening public health education in China is one of the most important measures to prevent and control anthrax.

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

PubMed

Barro, Alassane S; Fegan, Mark; Moloney, Barbara; Porter, Kelly; Muller, Janine; Warner, Simone; Blackburn, Jason K

2016-06-01

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

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

PubMed

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

2014-08-01

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

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

PubMed Central

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

2014-01-01

Summary 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 titer 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 worldwide, 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 titers and developed three increasingly conservative models to determine endpoint titers with more rigorous, objective mensuration. Between 52-87% of zebra, 0-15% of springbok, and 3-52% of elephants had measurable anti-anthrax antibody titers, 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 immunomodulators and affect population dynamics through indirect immunological and co-infection effects. In addition, with our three endpoint titer models, we introduce more mensuration rigor into serological antibody assays, even under the often-restrictive conditions that come with adapting laboratory immunology methods to wild systems. With these methods we identified significantly more zebras responding immunologically to anthrax than have previous studies using less comprehensive titer analyses. PMID:24499424

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

PubMed Central

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

2013-01-01

Introduction From August 2009 to October 2010, International Centre for Diarrheal Disease Research, Bangladesh and the Institute of Epidemiology, Disease Control and Research together investigated 14 outbreaks of anthrax which included 140 animal and 273 human cases in 14 anthrax-affected villages. Our investigation objectives were to explore the context in which these outbreaks occurred, including livestock rearing practices, human handling of sick and dead animals, and the anthrax vaccination program. Methods Field anthropologists used qualitative data-collection tools, including 15 hours of unstructured observations, 11 key informant interviews, 32 open-ended interviews, and 6 group discussions in 5 anthrax-affected villages. Results Each cattle owner in the affected communities raised a median of six ruminants on their household premises. The ruminants were often grazed in pastures and fed supplementary rice straw, green grass, water hyacinth, rice husk, wheat bran, and oil cake; lactating cows were given dicalcium phosphate. Cattle represented a major financial investment. Since Islamic law forbids eating animals that die from natural causes, when anthrax-infected cattle were moribund, farmers often slaughtered them on the household premises while they were still alive so that the meat could be eaten. Farmers ate the meat and sold it to neighbors. Skinners removed and sold the hides from discarded carcasses. Farmers discarded the carcasses and slaughtering waste into ditches, bodies of water, or open fields. Cattle in the affected communities did not receive routine anthrax vaccine due to low production, poor distribution, and limited staffing for vaccination. Conclusion Slaughtering anthrax-infected animals and disposing of butchering waste and carcasses in environments where ruminants live and graze, combined with limited vaccination, provided a context that permitted repeated anthrax outbreaks in animals and humans. Because of strong financial incentives, slaughtering moribund animals and discarding carcasses and waste products will likely continue. Long-term vaccination coverage for at-risk animal populations may reduce anthrax infection. PMID:24298326

Changing Patterns of Human Anthrax in Azerbaijan during the Post-Soviet and Preemptive Livestock Vaccination Eras

PubMed Central

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

2014-01-01

We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of +11.95% from 1984 to 1995 followed by declining rate of −35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated “One Health” approach that takes into account the changing geographic distribution of the disease. PMID:25032701

Pathology and pathophysiology of inhalational anthrax in a guinea pig model.

PubMed

Savransky, Vladimir; Sanford, Daniel C; Syar, Emily; Austin, Jamie L; Tordoff, Kevin P; Anderson, Michael S; Stark, Gregory V; Barnewall, Roy E; Briscoe, Crystal M; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris; Skiadopoulos, Mario H

2013-04-01

Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's "Animal Rule." However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 10(4) spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.

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

PubMed Central

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

2015-01-01

Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63 × 10−6 μM (0.551 ng/ml) for PA83 and 2.51 × 10−5 μM (1.58 ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through use of monoclonal antibodies to detect PA and LF in the lethal toxin complex. PMID:24857756

Anthrax vaccination in the Millennium Cohort: validation and measures of health.

PubMed

Smith, Besa; Leard, Cynthia A; Smith, Tyler C; Reed, Robert J; Ryan, Margaret A K

2007-04-01

In 1998, the United States Department of Defense initiated the Anthrax Vaccine Immunization Program. Concerns about vaccine-related adverse health effects followed, prompting several studies. Although some studies used self-reported vaccination data, the reliability of such data has not been established. The purpose of this study was to compare self-reported anthrax vaccination to electronic vaccine records among a large military cohort and to evaluate the relationship between vaccine history and health outcome data. Between September 2005 and February 2006 self-reported anthrax vaccination was compared to electronic records for 67,018 participants enrolled in the Millennium Cohort Study between 2001 and 2003 using kappa statistics. Multivariable modeling investigated vaccination concordance as it pertains to subjective health (functional status) and objective health (hospitalization) metrics. Greater than substantial agreement (kappa=0.80) was found between self-report and electronic recording of anthrax vaccination. Of all participants with electronic documentation of anthrax vaccination, 98% self-reported being vaccinated; and of all participants with no electronic record of vaccination, 90% self-reported not receiving a vaccination. There were no differences between vaccinated and unvaccinated participants in overall measures of health. Only the subset of participants who self-reported anthrax vaccination, but had no electronic confirmation, differed from others in the cohort, with consistently lower measures of health as indicated by Medical Outcomes Study 36-Item Short Form Health Survey for Veterans (SF-36V) scores. These results indicate that military members accurately recall their anthrax vaccinations. Results also suggest that anthrax vaccination among Millennium Cohort participants is not associated with self-reported health problems or broad measures of health problems severe enough to require hospitalization. Service members who self-report vaccination with no electronic documentation of vaccination, however, report lower measures of physical and mental health and deserve further research.

Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model

PubMed Central

Savransky, Vladimir; Sanford, Daniel C.; Syar, Emily; Austin, Jamie L.; Tordoff, Kevin P.; Anderson, Michael S.; Stark, Gregory V.; Barnewall, Roy E.; Briscoe, Crystal M.; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris

2013-01-01

Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule.” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 104 spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans. PMID:23357384

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

PubMed

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

2007-01-01

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

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review

PubMed Central

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

2016-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident. PMID:26690378

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

PubMed

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

2015-01-01

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

Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident.

PubMed

Bower, William A; Hendricks, Katherine; Pillai, Satish; Guarnizo, Julie; Meaney-Delman, Dana

2015-12-04

In 2014, CDC published updated guidelines for the prevention and treatment of anthrax (Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20[2]. Available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). These guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax in conventional medical settings. An aerosolized release of Bacillus anthracis spores over densely populated areas could become a mass-casualty incident. To prepare for this possibility, the U.S. government has stockpiled equipment and therapeutics (known as medical countermeasures [MCMs]) for anthrax prevention and treatment. However, previously developed, publicly available clinical recommendations have not addressed the use of MCMs or clinical management during an anthrax mass-casualty incident, when the number of patients is likely to exceed the ability of the health care infrastructure to provide conventional standards of care and supplies of MCMs might be inadequate to meet the demand required. To address this gap, in 2013, CDC conducted a series of systematic reviews of the scientific literature on anthrax to identify evidence that could help clinicians and public health authorities set guidelines for intravenous antimicrobial and antitoxin use, diagnosis of anthrax meningitis, and management of common anthrax-specific complications in the setting of a mass-casualty incident. Evidence from these reviews was presented to professionals with expertise in anthrax, critical care, and disaster medicine during a series of workgroup meetings that were held from August 2013 through March 2014. In March 2014, a meeting was held at which 102 subject matter experts discussed the evidence and adapted the existing best practices guidance to a clinical use framework for the judicious, efficient, and rational use of stockpiled MCMs for the treatment of anthrax during a mass-casualty incident, which is described in this report. This report addresses elements of hospital-based acute care, specifically antitoxins and intravenous antimicrobial use, and the diagnosis and management of common anthrax-specific complications during a mass-casualty incident. The recommendations in this report should be implemented only after predefined triggers have been met for shifting from conventional to contingency or crisis standards of care, such as when the magnitude of cases might lead to impending shortages of intravenous antimicrobials, antitoxins, critical care resources (e.g., chest tubes and chest drainage systems), or diagnostic capability. This guidance does not address primary triage decisions, anthrax postexposure prophylaxis, hospital bed or workforce surge capacity, or the logistics of dispensing MCMs. Clinicians, hospital administrators, state and local health officials, and planners can use these recommendations to assist in the development of crisis protocols that will ensure national preparedness for an anthrax mass-casualty incident.

Anthrax lethal factor inhibitors as potential countermeasure of the infection.

PubMed

Kumar, B V S Suneel; Malik, Siddharth; Grandhi, Pradeep; Dayam, Raveendra; Sarma, J A R P

2014-01-01

Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. Three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). Anthrax toxin is composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Protective antigen mediates the entry of Lethal Factor/Edema Factor into the cytosol of host cells. Lethal factor (LF) inactivates mitogen-activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defenses. In the past few years, extensive studies are undertaken to design inhibitors targeting LF. The current review focuses on the small molecule inhibitors targeting LF activity and its structure activity relationships (SAR).

Recent Advances in the Development of an Improved, Human Anthrax Vaccine

DTIC Science & Technology

1988-03-01

ology of toxin and capsule production and mode component of gram-negative endotoxin, trehalose of action, the improved methods developed for...im- for their safety and efficacy in potentiating immu- munoprophylaxis ot inhalation anthrax. - Abstr. nity to anthrax. Ann. Meeting. Am. Soc

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

PubMed

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

2014-02-01

Protective antigen (PA) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. Previously, we found that the 2β2-2β3 loop of PA contains a dominant neutralizing epitope, the SFFD. We successfully inserted the 2β2-2β3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein. The resulting fusion protein, termed HBc-N144-PA-loop2 (HBcL2), can effectively produce anthrax specific protective antibodies in an animal model. However, the protective immunity caused by HBcL2 could still be improved. In this research, we removed amino acids 79-81 from the HBc MIR of the HBcL2. This region was previously reported to be the major B cell epitope of HBc, and in keeping with this finding, we observed that the short deletion in the MIR not only diminished the intrinsic immunogenicity of HBc but also stimulated a higher titer of anthrax specific immunity. Most importantly, this deletion led to the full protection of the immunized mice against a lethal dose anthrax toxin challenge. We supposed that the conformational changes which occurred after the short deletion and foreign insertion in the MIR of HBc were the most likely reasons for the improvement in the immunogenicity of the HBc-based anthrax epitope vaccine. Copyright © 2013 Elsevier GmbH. All rights reserved.

Predicting disease risk, identifying stakeholders, and informing control strategies: A case study of anthrax in Montana

PubMed Central

Morris, Lillian R.; Blackburn, Jason K.

2018-01-01

Infectious diseases that affect wildlife and livestock are challenging to manage, and can lead to large scale die offs, economic losses, and threats to human health. The management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high risk landscapes. This study focuses on anthrax, caused by the bacterium Bacillus anthracis, risk to wildlife and livestock in Montana. There is a history of anthrax in Montana, but the spatial extent of disease risk and subsequent wildlife species at risk are not known. Our objective was to predict the potential geographic distribution of anthrax risk across Montana, identify wildlife species at risk and their distributions, and define stakeholders. We used an ecological niche model to predict the potential distribution of anthrax risk. We overlaid susceptible wildlife species distributions and land ownership delineations on our risk map. We found that there was an extensive region across Montana predicted as potential anthrax risk. These potentially risky landscapes overlapped the ranges of all 6 ungulate species considered in the analysis and livestock grazing allotments, and this overlap was on public and private land for all species. Our findings suggest that there is the potential for a multi species anthrax outbreak on multiple landscapes across Montana. Our potential anthrax risk map can be used to prioritize landscapes for surveillance and for implementing livestock vaccination programs. PMID:27169560

Predicting Disease Risk, Identifying Stakeholders, and Informing Control Strategies: A Case Study of Anthrax in Montana.

PubMed

Morris, Lillian R; Blackburn, Jason K

2016-06-01

Infectious diseases that affect wildlife and livestock are challenging to manage and can lead to large-scale die-offs, economic losses, and threats to human health. The management of infectious diseases in wildlife and livestock is made easier with knowledge of disease risk across space and identifying stakeholders associated with high-risk landscapes. This study focuses on anthrax, caused by the bacterium Bacillus anthracis, risk to wildlife and livestock in Montana. There is a history of anthrax in Montana, but the spatial extent of disease risk and subsequent wildlife species at risk are not known. Our objective was to predict the potential geographic distribution of anthrax risk across Montana, identify wildlife species at risk and their distributions, and define stakeholders. We used an ecological niche model to predict the potential distribution of anthrax risk. We overlaid susceptible wildlife species distributions and land ownership delineations on our risk map. We found that there was an extensive region across Montana predicted as potential anthrax risk. These potentially risky landscapes overlapped the ranges of all 6 ungulate species considered in the analysis and livestock grazing allotments, and this overlap was on public and private land for all species. Our findings suggest that there is the potential for a multi-species anthrax outbreak on multiple landscapes across Montana. Our potential anthrax risk map can be used to prioritize landscapes for surveillance and for implementing livestock vaccination programs.

Jamming Attack in Wireless Sensor Network: From Time to Space

NASA Astrophysics Data System (ADS)

Sun, Yanqiang; Wang, Xiaodong; Zhou, Xingming

Classical jamming attack models in the time domain have been proposed, such as constant jammer, random jammer, and reactive jammer. In this letter, we consider a new problem: given k jammers, how does the attacker minimize the pair-wise connectivity among the nodes in a Wireless Sensor Network (WSN)? We call this problem k-Jammer Deployment Problem (k-JDP). To the best of our knowledge, this is the first attempt at considering the position-critical jamming attack against wireless sensor network. We mainly make three contributions. First, we prove that the decision version of k-JDP is NP-complete even in the ideal situation where the attacker has full knowledge of the topology information of sensor network. Second, we propose a mathematical formulation based on Integer Programming (IP) model which yields an optimal solution. Third, we present a heuristic algorithm HAJDP, and compare it with the IP model. Numerical results show that our heuristic algorithm is computationally efficient.

Inmate's rape suit is viable despite missing paperwork.

PubMed

1999-10-29

An appeals court has reinstated a rape suit filed by an inmate who did not follow procedures when filing his complaint. The 6th U.S. Circuit Court of Appeals reinstated the suit by [name removed], who claims officials of the Ohio Department of Corrections (DOC) were deliberately indifferent to his safety and provided inadequate care after he was attacked by a fellow inmate. The case was originally dismissed on the grounds that [name removed] filed his lawsuit before filing a grievance form as required by the Prison Litigation Reform Act of 1996. The 6th Circuit ruled that [name removed] complied with the law by writing letters to several prison officials inquiring about his attacker's HIV status and possible charges against the attacker.

ANTHRAX PROBLEM IN MASSACHUSETTS

PubMed Central

Osborn, Stanley H.

1920-01-01

Federal regulations do not prevent importation of anthrax infected material. This author suggests anthrax surveys in countries of origin of materials, quarantine of all hides, wool and hair from suspected areas, disinfection of these at places of origin and sanitary care here of wastes from hide and wool industrial establishments. Imagesp665-a PMID:18010353

INTER-ALPHA INHIBITOR PROTEINS: A NOVEL THERAPEUTIC STRATEGY FOR EXPERIMENTAL ANTHRAX INFECTION

PubMed Central

Opal, Steven M.; Lim, Yow-Pin; Cristofaro, Patricia; Artenstein, Andrew W.; Kessimian, Noubar; DelSesto, David; Parejo, Nicolas; Palardy, John E.; Siryaporn, Edward

2010-01-01

Human inter-alpha-inhibitor proteins (IaIp) are endogenous human plasma proteins that function as serine protease inhibitors. IaIp can block the systemic release of proteases in sepsis and block furin-mediated assembly of protective antigen, an essential stop in the intracellular delivery of the anthrax exotoxins, lethal toxin and edema toxin. IaIp administered on hour or up to 24 hours after spore challenge with Bacillus anthracis Sterne strain protected mice from lethality if administered with antimicrobial therapy (p<.001). These human plasma proteins possess combined actions against anthrax as general inhibitors of excess serine proteases in sepsis and specific inhibitors of anthrax toxin assembly. IaIp could represent a novel adjuvant therapy for the treatment of established anthrax infection. PMID:20523269

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

A longitudinal study of UK military personnel offered anthrax vaccination: informed choice, symptom reporting, uptake and pre-vaccination health.

PubMed

Murphy, D; Marteau, T M; Wessely, S

2012-02-01

To determine longer term health outcome in a cohort of UK service personnel who received the anthrax vaccination. We conducted a three year follow up of UK service personnel all of whom were in the Armed Forces at the start of the Iraq War. 3206 had been offered the anthrax vaccination as part of preparations for the 2003 invasion of Iraq. A further 1190 individuals who did not deploy to Iraq in 2003 were subsequently offered the vaccination as part of later deployments, and in whom we therefore had prospective pre-exposure data. There was no overall adverse health effect following receipt of the anthrax vaccination, with follow up data ranging from three to six years following vaccination. The previous retrospective association between making an uninformed choice to receive the anthrax vaccination and increased symptom reporting was replicated within a longitudinal sample where pre-vaccination health was known. Anthrax vaccination was not associated with long term adverse health problems. However, symptoms were associated with making an uninformed choice to undergo the vaccination. The results are important both for the safety of the vaccine and for future policies should anthrax vaccination be required in either military or non military populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Attribution of Spear Phishing Attacks: A Literature Survey

DTIC Science & Technology

2013-08-01

header of an email, verbally informed by another person, or easily ascertained via the handwriting of the text. In a few specific cases, this...scene would be scrutinised, based on both the handwriting and the content of the letter, to identify a suspect. The goal of this phase is to establish

The Taliban Insurgency and an Analysis of ’Shabnamah’ (Night Letters)

DTIC Science & Technology

2007-09-01

regular terminology used by al-Qaeda. It proclaims a clash of civilisations . The declaration accuses the ‘crusaders and their domestic servants’ of...In Violence: Foreign Support Seen Behind Attacks That Mimic Those in Iraq’, Christian Science Monitor, 28 Nov. 2005, p.1. 56. Eric Schmitt

Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of Turkey.

PubMed

Denk, Affan; Tartar, Ayse Sagmak; Ozden, Mehmet; Demir, Betul; Akbulut, Ayhan

2016-09-01

Anthrax is an endemic disease in developing countries. Human cases are usually associated with animal products. About 95% of naturally acquired cases are cutaneous anthrax. In this study, cutaneous anthrax cases from the Elazig province (the Eastern Anatolian region) of Turkey seen in our hospital within a 6-year period were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome. Twenty-eight patients with cutaneous anthrax observed between January 2009 and December 2014 were investigated retrospectively. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless, ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 years (age range 17-65 years). The patients have an incubation period in the range of 1-9 days (mean 4.6 ± 0.5 days). The cases were seen between April and November of each year during the study period. Twenty-three cases (82%) had a history of contact with animals or animal products. Twenty patients (71.4%) showed malignant pustules and eight (28.6%) malignant edema. Bacillus anthracis was isolated in three cases (10.7%) and Gram stain smear were positive in five cases (17.8%). All patients were treated successfully with penicillin or ciprofloxacin. Systemic corticosteroids were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered. Anthrax is still a serious public health problem in Turkey. Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, edema, and a history of contact with animals or animal products are observed in an individual. Early and correct diagnosis significantly affects course of the disease. Protective precautions such as vaccination of animals against anthrax and education of the population would reduce the incidence of the disease.

Anthrax

DTIC Science & Technology

2009-01-01

antimicrobials listed below) Initial therapye (intravenous dosing) Oral dosing Initial therapy (intravenous) IV treatment initially Switch to oral...high index of suspicion for anthrax, initiation of therapy should not be delayed for results of these confirmatory tests. 1. MICROBIOLOGICAL TESTS...Sputum specimens from inhalational anthrax patients should be plated on chocolate agar, SBA, and MAC. Cultures will show isolated B. anthracis

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

DTIC Science & Technology

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY... livestock remains in the lot. (c) Apparently healthy livestock (other than hogs) from a lot in which anthrax is detected, and any apparently healthy livestock which have been treated with anthrax biologicals...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY... livestock remains in the lot. (c) Apparently healthy livestock (other than hogs) from a lot in which anthrax is detected, and any apparently healthy livestock which have been treated with anthrax biologicals...

Anthrax Spores under a microscope

NASA Technical Reports Server (NTRS)

2003-01-01

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

Human Cutaneous Anthrax, Georgia 2010–2012

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-01-01

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

A Mathematical Model of Anthrax Transmission in Animal Populations.

PubMed

Saad-Roy, C M; van den Driessche, P; Yakubu, Abdul-Aziz

2017-02-01

A general mathematical model of anthrax (caused by Bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. The basic reproduction number [Formula: see text] is calculated, and existence of a unique endemic equilibrium is established for [Formula: see text] above the threshold value 1. Using data from the literature, elasticity indices for [Formula: see text] and type reproduction numbers are computed to quantify anthrax control measures. Including only herbivorous animals, anthrax is eradicated if [Formula: see text]. For these animals, oscillatory solutions arising from Hopf bifurcations are numerically shown to exist for certain parameter values with [Formula: see text] and to have periodicity as observed from anthrax data. Including carnivores and assuming no disease-related death, anthrax again goes extinct below the threshold. Local stability of the endemic equilibrium is established above the threshold; thus, periodic solutions are not possible for these populations. It is shown numerically that oscillations in spore growth may drive oscillations in animal populations; however, the total number of infected animals remains about the same as with constant spore growth.

Source and risk factors of a cutaneous anthrax outbreak, Jiangsu, Eastern China, 2012.

PubMed

Hu, J L; Cui, L L; Bao, C J; Tan, Z M; Rutherford, S; Ying, L; Zhang, M L; Zhu, F C

2016-09-01

Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas.

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

PubMed

Ascough, Stephanie; Altmann, Daniel Martin

2015-06-01

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

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

PubMed

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

2016-01-01

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

[Scientific substantiation of sizes of sanitary protection zones of anthrax burial sites based on the comprehensive evaluation of risk factors].

PubMed

Kartavaya, S A; Simonova, E G; Loktionova, M N; Kolganova, O A; Ladny, V I; Raichich, S R

In the Russian Federation anthrax epizootics are still being registered among animals as well as epidemic foci of the population. This situation is linked to natural reservoirs of the pathogen - numerous anthrax burial sites which belong to class I of dangerous objects. In this connection, a one-kilometer sanitary protective zone is required according to current Russian Federation legislation. As a result, a significant land of the country is unsuitable for any agricultural use. Meanwhile, epizootologo-epidemiological observations indicate to that different anthrax burial sites differ in their characteristics and represent varying degrees of the risk. In connection with the development of the agricultural sector, intensive construction and the development of new and abandoned areas there is a need of creating unified approaches to assess the risk of anthrax burial sites, as well as to determine the size of sanitary protection zones based on the risk assessment. This article represents an original methodology to assess the actual danger of anthrax burial sites. It is based on a comprehensive multi-factor quantity-related risk assessment, described by a model that accounting the importance of each study for natural, social and biological factors. Undertaking this methodology allowed to reveal a degree of danger of anthrax burial sites located in different territories of the Russian Federation, and helped to substantiate the dimensions of their sanitary protection zones.

Bioethics, bioweapons and the microbiologist.

PubMed

Anaya-Velázquez, Fernando

2002-01-01

The analysis of behavior of man in the field of biology is carried out through bioethics, considered the science of the survival. In the microbiology, there are numerous discoveries related with pathogenic microorganisms, including those that can be used as weapons in a biological war or in an attack considered bioterrorism. The scientist involved in microbiology can participate with his knowledge in the development and improvement of bioweapons, however from the point of view of bioethics it is not acceptable that he works in an investigation related with these topics, because the defense research can evolve in offensive one. The war is an antisurvival activity, therefore it is not acceptable. In the same way, the biological weapons composed with virus, fungi or alive bacteria, or with toxins from them, neither they are morally accepted. After the terrorist attacks with anthrax in the United States in 2001, the world scientific community in the field of microbiology should show against the use of the microorganisms like bioweapons, at the time of promoting the idea that the responsible use for the microorganisms is a moral imperative for all microbiologists around the world, since the biological weapons are a threat for the human life.

Biological warfare agents

PubMed Central

Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

2010-01-01

The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

Anthrax vaccine associated deaths in miniature horses.

PubMed

Wobeser, Bruce K

2015-04-01

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

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

PubMed

Keim, Paul; Grunow, Roland; Vipond, Richard; Grass, Gregor; Hoffmaster, Alex; Birdsell, Dawn N; Klee, Silke R; Pullan, Steven; Antwerpen, Markus; Bayer, Brittany N; Latham, Jennie; Wiggins, Kristin; Hepp, Crystal; Pearson, Talima; Brooks, Tim; Sahl, Jason; Wagner, David M

2015-11-01

Anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. Injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple European countries and this outbreak has been difficult to trace back to a source. We took a molecular epidemiological approach in understanding this disease outbreak, including whole genome sequencing of Bacillus anthracis isolates from the anthrax victims. We also screened two large strain repositories for closely related strains to provide context to the outbreak. Analyzing 60 Bacillus anthracis isolates associated with injectional anthrax cases and closely related reference strains, we identified 1071 Single Nucleotide Polymorphisms (SNPs). The synapomorphic SNPs (350) were used to reconstruct phylogenetic relationships, infer likely epidemiological sources and explore the dynamics of evolving pathogen populations. Injectional anthrax genomes separated into two tight clusters: one group was exclusively associated with the 2009-10 outbreak and located primarily in Scotland, whereas the second comprised more recent (2012-13) cases but also a single Norwegian case from 2000. Genome-based differentiation of injectional anthrax isolates argues for at least two separate disease events spanning > 12 years. The genomic similarity of the two clusters makes it likely that they are caused by separate contamination events originating from the same geographic region and perhaps the same site of drug manufacturing or processing. Pathogen diversity within single patients challenges assumptions concerning population dynamics of infecting B. anthracis and host defensive barriers for injectional anthrax. This work was supported by the United States Department of Homeland Security grant no. HSHQDC-10-C-00,139 and via a binational cooperative agreement between the United States Government and the Government of Germany. This work was supported by funds from the German Ministry of Defense (Sonderforschungsprojekt 25Z1-S-431,214). Support for sequencing was also obtained from Illumina, Inc. These sources had no role in the data generation or interpretation, and had not role in the manuscript preparation. We searched PubMed for any article published before Jun. 17, 2015, with the terms "Bacillus anthracis" and "heroin", or "injectional anthrax". Other than our previously published work (Price et al., 2012), we found no other relevant studies on elucidating the global phylogenetic relationships of B. anthracis strains associated with injectional anthrax caused by recreational heroin consumption of spore-contaminated drug. There were, however, publically available genome sequences of two strains involved (Price et al., 2012, Grunow et al., 2013) and the draft genome sequence of Bacillus anthracis UR-1, isolated from a German heroin user (Ruckert et al., 2012) with only limited information on the genotyping of closely related strains (Price et al., 2012, Grunow et al., 2013). 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.

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

NASA Astrophysics Data System (ADS)

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

Geographic information system (GIS) is a computer application system, which possesses the ability of manipulating spatial information and has been used in many fields related with the spatial information management. Many methods and models have been established for analyzing animal diseases distribution models and temporal-spatial transmission models. Great benefits have been gained from the application of GIS in animal disease epidemiology. GIS is now a very important tool in animal disease epidemiological research. Spatial analysis function of GIS can be widened and strengthened by using spatial statistical analysis, allowing for the deeper exploration, analysis, manipulation and interpretation of spatial pattern and spatial correlation of the animal disease. In this paper, we analyzed the cow anthrax spatial distribution characteristics in the target district A (due to the secret of epidemic data we call it district A) based on the established GIS of the cow anthrax in this district in combination of spatial statistical analysis and GIS. The Cow anthrax is biogeochemical disease, and its geographical distribution is related closely to the environmental factors of habitats and has some spatial characteristics, and therefore the correct analysis of the spatial distribution of anthrax cow for monitoring and the prevention and control of anthrax has a very important role. However, the application of classic statistical methods in some areas is very difficult because of the pastoral nomadic context. The high mobility of livestock and the lack of enough suitable sampling for the some of the difficulties in monitoring currently make it nearly impossible to apply rigorous random sampling methods. It is thus necessary to develop an alternative sampling method, which could overcome the lack of sampling and meet the requirements for randomness. The GIS computer application software ArcGIS9.1 was used to overcome the lack of data of sampling sites.Using ArcGIS 9.1 and GEODA to analyze the cow anthrax spatial distribution of district A. we gained some conclusions about cow anthrax' density: (1) there is a spatial clustering model. (2) there is an intensely spatial autocorrelation. We established a prediction model to estimate the anthrax distribution based on the spatial characteristic of the density of cow anthrax. Comparing with the true distribution, the prediction model has a well coincidence and is feasible to the application. The method using a GIS tool facilitates can be implemented significantly in the cow anthrax monitoring and investigation, and the space statistics - related prediction model provides a fundamental use for other study on space-related animal diseases.

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection*

PubMed Central

Vrentas, Catherine E.; Moayeri, Mahtab; Keefer, Andrea B.; Greaney, Allison J.; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H.; Shoemaker, Charles B.

2016-01-01

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LFN, EFN) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. PMID:27539858

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

PubMed Central

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

2012-01-01

Objective To simulate the neutron-based sterilisation of anthrax contamination by Monte Carlo N-particle (MCNP) 4C code. Methods 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 252Cf 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 1013 n s−1 with current technology. All these enable an effective and low-cost method of killing anthrax spores. Results 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. Conclusion The MCNP simulation indicates that a 10 min neutron irradiation from a 0.5 g 252Cf 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 >1013 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. PMID:22573293

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

PubMed

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 Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection.

PubMed

Vrentas, Catherine E; Moayeri, Mahtab; Keefer, Andrea B; Greaney, Allison J; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H; Shoemaker, Charles B

2016-10-07

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LF N , EF N ) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2015-03-01

Sporadic anthrax outbreaks have occurred in and around Uganda's Queen Elizabeth National Park (QENP) for years, affecting wildlife, domestic animals, and humans. Reported outbreaks (2004-2005 and 2010) in QENP collectively killed over 500 wild animals and over 400 domestic animals. A 2011 outbreak in Sheema district temporarily froze local markets while killing two humans and seven bovines. One Health is multidisciplinary at its core, yet studies sometimes focus on the effects of animals on human health to the detriment of investigating the surrounding ecological and cultural contexts. Participatory methods connect problems - such as disease - to their context. A multidisciplinary team used participatory epidemiology and conventional structured questionnaires to investigate the impacts of anthrax on human livelihoods and the related perceptions of conservation, public health, and veterinary health efforts in the QENP area. Proximities to previous anthrax outbreaks and to QENP were treated as risk factors in the collection and evaluation of data. Participants' feedback indicates that anthrax prevalence may be greater than officially reported. Community member perceptions about anthrax and other diseases appear to be more closely related to their proximity to QENP than their proximity to anthrax outbreaks. Neither risk factor had a strong effect on knowledge of disease, nor any effect on behaviors associated with disease response or control. Instead, participants reported that social pressures, the economics of poverty, and the lack of health and veterinary infrastructure highly influenced responses to disease. The complex connections between the social needs and the economic context of these communities seem to be undermining current anthrax control and education measures. This livelihood-based decision-making may be unlikely to respond to educational intervention alone. This study provides a strong base for further research and for improvements in effective disease control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bacteriophage T4 as a Nanoparticle Platform to Display and Deliver Pathogen Antigens: Construction of an Effective Anthrax Vaccine.

PubMed

Tao, Pan; Li, Qin; Shivachandra, Sathish B; Rao, Venigalla B

2017-01-01

Protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. However, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. The bacteriophage T4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. Therefore, it offers a strong promise as a novel antigen delivery system. Currently Bacillus anthracis, the causative agent of anthrax, is a serious biothreat agent and no FDA-approved anthrax vaccine is available for mass vaccination. Here, we describe a potential anthrax vaccine using a T4 capsid platform to display and deliver the 83 kDa protective antigen, PA, a key component of the anthrax toxin. This T4 vaccine platform might serve as a universal antigen delivery system that can be adapted to develop vaccines against any infectious disease.

Anthrax Pathogenesis.

PubMed

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

2015-01-01

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

Physical and Chemical Analytical Analysis: A key component of Bioforensics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velsko, S P

The anthrax letters event of 2001 has raised our awareness of the potential importance of non-biological measurements on samples of biological agents used in a terrorism incident. Such measurements include a variety of mass spectral, spectroscopic, and other instrumental techniques that are part of the current armamentarium of the modern materials analysis or analytical chemistry laboratory. They can provide morphological, trace element, isotopic, and other molecular ''fingerprints'' of the agent that may be key pieces of evidence, supplementing that obtained from genetic analysis or other biological properties. The generation and interpretation of such data represents a new domain of forensicmore » science, closely aligned with other areas of ''microbial forensics''. This paper describes some major elements of the R&D agenda that will define this sub-field in the immediate future and provide the foundations for a coherent national capability. Data from chemical and physical analysis of BW materials can be useful to an investigation of a bio-terror event in two ways. First, it can be used to compare evidence samples collected at different locations where such incidents have occurred (e.g. between the powders in the New York and Washington letters in the Amerithrax investigation) or between the attack samples and those seized during the investigation of sites where it is suspected the material was manufactured (if such samples exist). Matching of sample properties can help establish the relatedness of disparate incidents, and mis-matches might exclude certain scenarios, or signify a more complex etiology of the events under investigation. Chemical and morphological analysis for sample matching has a long history in forensics, and is likely to be acceptable in principle in court, assuming that match criteria are well defined and derived from known limits of precision of the measurement techniques in question. Thus, apart from certain operational issues (such as how to prioritize such measurements in the face of limited sample availability, or how to render samples safe for handling in the analytical laboratory,) instrumental analysis of biological agents for purposes of sample matching alone is unlikely to present fundamental problems that require extensive research and development investments. The second way that the data generated by instrumental analysis can be useful to an investigation is through inferences that can be drawn regarding the processes used to grow and ''weaponize'' the agent. In contrast to the case of sample matching, there are significant R&D challenges associated with developing a robust capability that will reliably permit such inferential uses of instrumental data. Elaborating these challenges occupies the major portion of this paper.« less

Do Specific Classroom Reading Activities Predict English Language Learners' Later Reading Achievement?

ERIC Educational Resources Information Center

Swanson, H. Lee; Orosco, Michael J.; Kudo, Milagros Fatima

2017-01-01

This study investigated the relationship between elementary classroom (N = 50) reading activities in Year 1 and reading performance (i.e., passage comprehension, letter-word identification, and word attack) 1 year later for English language learners (ELLs; N = 270). A cross-classification hierarchical model indicated that compared to other reading…

Roots of terrorism: a reassessment after September 11th

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilat, Joseph F.

2002-01-01

The brutal terrorist attacks of September 11th, the anthrax attacks that followed and growing knowledge of al Qaeda's pursuit of nuclear, biological and chemical weapons have not only intensified concerns about terrorism but also created doubts about our understanding of terrorism. These attacks were in many ways unprecedented, and ultimately raise the question of the roots or causes of terrorism. Historically and today, there have been divergent views on this question, which reflect philosophical, religious, political, sociological and other differences. These differences are not merely academic, as they can affect our understanding of both the threat and of responses tomore » terrorism in the aftermath of September 11th, Terrorism is too complex and diverse a phenomenon to speak easily of causes. But we may be able to discern the causes of specific acts. Our response to 9/11 and other acts of terrorism will be affected by our understanding of their causes. If 9/11 was caused by US Middle East policies, the response must involve a review of these policies. If it is a backlash against globalization, the response must address the realities underlying anti-globalization sentiments. Addressing causes will not in any case end terrorism, and addressing the wrong causes will be counterproductive. Actions to reduce those conditions that create support for terrorism and aid its recruitment, which need to be clearly identified, are critical in any counterterrorism strategy. So we must understand the reasons for terrorism and, in particular, for the attacks of September 11th.T his paper will look at the question of the roots of terrorism and then look to the specific case of 911 and its aftermath, with a special view to the impact of globalization.« less

Anthrax: Diagnosis

MedlinePlus

... Laboratory Testing Confirming Anthrax Through the Laboratory Response Network FAQs Information for Specific Groups Laboratory Professionals Collecting Specimens Recommended Specimens Worker Safety ...

Treatment of Anthrax Disease Frequently Asked Questions

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.

Tumor Targeting and Drug Delivery by Anthrax Toxin.

PubMed

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.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, Diane E.; Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA; Hoover, Benjamin

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-BL6more » 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-tumor activity of protease-activated anthrax toxins were evaluated. • All anthrax toxin variants exhibited potent systemic anti-tumor activity in mice. • A dual MMP/uPA-activated anthrax toxin displayed a superior safety profile. • Clinical development of a dual MMP/uPA-activated anthrax toxin is feasible.« less

Agroterrorism: where are we in the ongoing war on terrorism?

PubMed

Crutchley, Tamara M; Rodgers, Joel B; Whiteside, Heustis P; Vanier, Marty; Terndrup, Thomas E

2007-03-01

The U.S. agricultural infrastructure is one of the most productive and efficient food-producing systems in the world. Many of the characteristics that contribute to its high productivity and efficiency also make this infrastructure extremely vulnerable to a terrorist attack by a biological weapon. Several experts have repeatedly stated that taking advantage of these vulnerabilities would not require a significant undertaking and that the nation's agricultural infrastructure remains highly vulnerable. As a result of continuing criticism, many initiatives at all levels of government and within the private sector have been undertaken to improve our ability to detect and respond to an agroterrorist attack. However, outbreaks, such as the 1999 West Nile outbreak, the 2001 anthrax attacks, the 2003 monkeypox outbreak, and the 2004 Escherichia coli O157:H7 outbreak, have demonstrated the need for improvements in the areas of communication, emergency response and surveillance efforts, and education for all levels of government, the agricultural community, and the private sector. We recommend establishing an interdisciplinary advisory group that consists of experts from public health, human health, and animal health communities to prioritize improvement efforts in these areas. The primary objective of this group would include establishing communication, surveillance, and education benchmarks to determine current weaknesses in preparedness and activities designed to mitigate weaknesses. We also recommend broader utilization of current food and agricultural preparedness guidelines, such as those developed by the U.S. Department of Agriculture and the U.S. Food and Drug Administration.

Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase from Bacillus cereus*

PubMed Central

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

2012-01-01

We identified Certhrax, the first anthrax-like mART toxin from the pathogenic G9241 strain of Bacillus cereus. Certhrax shares 31% sequence identity with anthrax lethal factor from Bacillus anthracis; however, we have shown that the toxicity of Certhrax resides in the mART domain, whereas anthrax uses a metalloprotease mechanism. Like anthrax lethal factor, Certhrax was found to require protective antigen for host cell entry. This two-domain enzyme was shown to be 60-fold more toxic to mammalian cells than anthrax lethal factor. Certhrax localizes to distinct regions within mouse RAW264.7 cells by 10 min postinfection and is extranuclear in its cellular location. Substitution of catalytic residues shows that the mART function is responsible for the toxicity, and it binds NAD+ with high affinity (KD = 52.3 ± 12.2 μm). We report the 2.2 Å Certhrax structure, highlighting its structural similarities and differences with anthrax lethal factor. We also determined the crystal structures of two good inhibitors (P6 (KD = 1.7 ± 0.2 μm, Ki = 1.8 ± 0.4 μm) and PJ34 (KD = 5.8 ± 2.6 μm, Ki = 9.6 ± 0.3 μm)) in complex with Certhrax. As with other toxins in this family, the phosphate-nicotinamide loop moves toward the NAD+ binding site with bound inhibitor. These results indicate that Certhrax may be important in the pathogenesis of B. cereus. PMID:22992735

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

PubMed Central

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

2015-01-01

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay. PMID:26426050

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

PubMed

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

2015-09-29

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

Biological Incident Operations: A Guide for Law Enforcement

DTIC Science & Technology

2004-09-01

organisms. Bacteria can vary in size and shape and some have the capability of forming spores . Spores are much hardier since they are more capable of...unintentional dissemination of a biological agent occurred in the anthrax mailings (October 2001) when anthrax spores cross-contaminated machinery...indicate the presence of Bacillus anthracis (anthrax) and Yersinia pestis (plague). Washington DC emergency personnel responded to the incident. As a

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

DTIC Science & Technology

2006-04-01

be- known severe adverse health effects , excluding mortality and pregnancy-related outcomes , associated with anthrax vaccination. Outcomes were...January 1, 1998 to December 31, 2001. Study outcomes included hospitalizations due to any-cause, 14 broad International Classification of Diseases...talization outcomes studied. Although there was no apparent increase in risk of morbidity in this study population, the relationship between anthrax

Maximum entropy modeling risk of anthrax in the Republic of Kazakhstan.

PubMed

Abdrakhmanov, S K; Mukhanbetkaliyev, Y Y; Korennoy, F I; Sultanov, A A; Kadyrov, A S; Kushubaev, D B; Bakishev, T G

2017-09-01

The objective of this study was to zone the territory of the Republic of Kazakhstan (RK) into risk categories according to the probability of anthrax emergence in farm animals as stipulated by the re-activation of preserved natural foci. We used historical data on anthrax morbidity in farm animals during the period 1933 - 2014, collected by the veterinary service of the RK. The database covers the entire territory of the RK and contains 4058 anthrax outbreaks tied to 1798 unique locations. Considering the strongly pronounced natural focality of anthrax, we employed environmental niche modeling (Maxent) to reveal patterns in the outbreaks' linkages to specific combinations of environmental factors. The set of bioclimatic factors BIOCLIM, derived from remote sensing data, the altitude above sea level, the land cover type, the maximum green vegetation fraction (MGVF) and the soil type were examined as explanatory variables. The model demonstrated good predictive ability, while the MGVF, the bioclimatic variables reflecting precipitation level and humidity, and the soil type were found to contribute most significantly to the model. A continuous probability surface was obtained that reflects the suitability of the study area for the emergence of anthrax outbreaks. The surface was turned into a categorical risk map by averaging the probabilities within the administrative divisions at the 2nd level and putting them into four categories of risk, namely: low, medium, high and very high risk zones, where very high risk refers to more than 50% suitability to the disease re-emergence and low risk refers to less than 10% suitability. The map indicated increased risk of anthrax re-emergence in the districts along the northern, eastern and south-eastern borders of the country. It was recommended that the national veterinary service uses the risk map for the development of contra-epizootic measures aimed at the prevention of anthrax re-emergence in historically affected regions of the RK. The map can also be considered when developing large-scale construction projects in the areas comprising preserved soil foci of anthrax. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

2013-01-01

Background 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 typical and more unusual manifestations. Case presentations The first patient, a 55-year old man with HIV and hepatitis C virus co-infection, presented with severe pain in the right thigh and lower abdomen after injecting heroin into the right groin. Computed tomography and ultrasonographic examination of the abdomen and right thigh showed oedematous thickened peritoneum, distended oedematous mesentery and subcutaneous oedema of the right thigh. At admission the patient was afebrile but within 24 hours he progressed to severe septic shock and abdominal compartment syndrome. Cultures of blood and intraperitoneal fluid grew Bacillus anthracis. The patient was treated with meropenem, clindamycin, ciprofloxacin and metronidazole. Despite maximum supportive care including mechanical ventilation, vasopressor treatment and continuous veno-venous hemodiafiltration the patient died on day four. The second patient, a 39-year old man with chronic hepatitis C virus infection, presented with fever and a swollen right arm after injecting heroin into his right arm. The arm was swollen from the axilla to the wrist with tense and discoloured skin. He was initially septic with low blood pressure but responded to crystalloids. During the first week, swelling progressed and the patient developed massive generalised oedema with a weight gain of 40 kg. When blood cultures grew Bacillus anthracis antibiotic treatment was changed to meropenem, moxifloxacin and metronidazole, and on day 7 hydroxycloroquin was added. The patient responded to treatment and was discharged after 29 days. Conclusions These two heroin-associated anthrax cases from Denmark corroborate that heroin contaminated with anthrax spores may be a continuous source of injectional anthrax across Europe. Clinicians and clinical microbiologists need to stay vigilant and suspect anthrax in patients with a history of heroin use who present with soft tissue or generalised infection. Marked swelling of affected soft tissue or unusual intra-abdominal oedema should strengthen clinical suspicion. PMID:24004900

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

PubMed

Russell, Lene; Pedersen, Michael; Jensen, Andreas V; Søes, Lillian Marie; Hansen, Ann-Brit Eg

2013-09-03

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 typical and more unusual manifestations. The first patient, a 55-year old man with HIV and hepatitis C virus co-infection, presented with severe pain in the right thigh and lower abdomen after injecting heroin into the right groin. Computed tomography and ultrasonographic examination of the abdomen and right thigh showed oedematous thickened peritoneum, distended oedematous mesentery and subcutaneous oedema of the right thigh. At admission the patient was afebrile but within 24 hours he progressed to severe septic shock and abdominal compartment syndrome. Cultures of blood and intraperitoneal fluid grew Bacillus anthracis. The patient was treated with meropenem, clindamycin, ciprofloxacin and metronidazole. Despite maximum supportive care including mechanical ventilation, vasopressor treatment and continuous veno-venous hemodiafiltration the patient died on day four.The second patient, a 39-year old man with chronic hepatitis C virus infection, presented with fever and a swollen right arm after injecting heroin into his right arm. The arm was swollen from the axilla to the wrist with tense and discoloured skin. He was initially septic with low blood pressure but responded to crystalloids. During the first week, swelling progressed and the patient developed massive generalised oedema with a weight gain of 40 kg. When blood cultures grew Bacillus anthracis antibiotic treatment was changed to meropenem, moxifloxacin and metronidazole, and on day 7 hydroxycloroquin was added. The patient responded to treatment and was discharged after 29 days. These two heroin-associated anthrax cases from Denmark corroborate that heroin contaminated with anthrax spores may be a continuous source of injectional anthrax across Europe. Clinicians and clinical microbiologists need to stay vigilant and suspect anthrax in patients with a history of heroin use who present with soft tissue or generalised infection. Marked swelling of affected soft tissue or unusual intra-abdominal oedema should strengthen clinical suspicion.

Prophylaxis and treatment of pregnant women for emerging infections and bioterrorism emergencies.

PubMed

Cono, Joanne; Cragan, Janet D; Jamieson, Denise J; Rasmussen, Sonja A

2006-11-01

Emerging infectious disease outbreaks and bioterrorism attacks warrant urgent public health and medical responses. Response plans for these events may include use of medications and vaccines for which the effects on pregnant women and fetuses are unknown. Healthcare providers must be able to discuss the benefits and risks of these interventions with their pregnant patients. Recent experiences with outbreaks of severe acute respiratory syndrome, monkeypox, and anthrax, as well as response planning for bioterrorism and pandemic influenza, illustrate the challenges of making recommendations about treatment and prophylaxis for pregnant women. Understanding the physiology of pregnancy, the factors that influence the teratogenic potential of medications and vaccines, and the infection control measures that may stop an outbreak will aid planners in making recommendations for care of pregnant women during large-scale infectious disease emergencies.

Structural models used in real-time biosurveillance outbreak detection and outbreak curve isolation from noisy background morbidity levels

PubMed Central

Cheng, Karen Elizabeth; Crary, David J; Ray, Jaideep; Safta, Cosmin

2013-01-01

Objective We discuss the use of structural models for the analysis of biosurveillance related data. Methods and results Using a combination of real and simulated data, we have constructed a data set that represents a plausible time series resulting from surveillance of a large scale bioterrorist anthrax attack in Miami. We discuss the performance of anomaly detection with structural models for these data using receiver operating characteristic (ROC) and activity monitoring operating characteristic (AMOC) analysis. In addition, we show that these techniques provide a method for predicting the level of the outbreak valid for approximately 2 weeks, post-alarm. Conclusions Structural models provide an effective tool for the analysis of biosurveillance data, in particular for time series with noisy, non-stationary background and missing data. PMID:23037798

Climatic influence on anthrax suitability in warming northern latitudes.

PubMed

Walsh, Michael G; de Smalen, Allard W; Mor, Siobhan M

2018-06-18

Climate change is impacting ecosystem structure and function, with potentially drastic downstream effects on human and animal health. Emerging zoonotic diseases are expected to be particularly vulnerable to climate and biodiversity disturbance. Anthrax is an archetypal zoonosis that manifests its most significant burden on vulnerable pastoralist communities. The current study sought to investigate the influence of temperature increases on geographic anthrax suitability in the temperate, boreal, and arctic North, where observed climate impact has been rapid. This study also explored the influence of climate relative to more traditional factors, such as livestock distribution, ungulate biodiversity, and soil-water balance, in demarcating risk. Machine learning was used to model anthrax suitability in northern latitudes. The model identified climate, livestock density and wild ungulate species richness as the most influential features in predicting suitability. These findings highlight the significance of warming temperatures for anthrax ecology in northern latitudes, and suggest potential mitigating effects of interventions targeting megafauna biodiversity conservation in grassland ecosystems, and animal health promotion among small to midsize livestock herds.

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

PubMed

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.

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

PubMed Central

Lehman, Mark W.; Craig, Allen S.; Malama, Constantine; Kapina-Kany’anga, Muzala; Malenga, Philip; Munsaka, Fanny; Muwowo, Sergio; Shadomy, Sean

2017-01-01

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 hippopotamus 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. PMID:28820129

Anthrax of the Gastrointestinal Tract

DTIC Science & Technology

2002-07-01

partial immunity. * Chiang Mai University, Chiang Mai , Thailand; and †Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand T PERSPECTIVE...1982 in Chiang Mai , northern Thailand (25). A total of 52 cases of cutaneous anthrax and 24 cases of oropharyngeal anthrax were recognized in humans...was the case in the Chiang Mai outbreak (25). Only those who eat dishes that are raw or undercooked are exposed to infectious material. Disease is

Preparing South Carolina Emergency Departments for Mass Casualties with an Emphasis on the Planning Process

DTIC Science & Technology

2013-03-01

population for patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza 19 • 50 cases...disease, especially smallpox, anthrax, plague, tularemia , and influenza • 50 cases per million population for patients with symptoms of acute...an additional 1,548–2064 patients with symptoms of acute infectious disease, especially smallpox, anthrax, plague, tularemia , and influenza to be

Crystallographic studies of the Anthrax lethal toxin. Annual report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frederick, C.A.

1996-07-01

The lethal form of Anthrax results from the inhalation of anthrax spores. Death is primarily due to the effects of the lethal toxin (Protective Antigen (PA) + Lethal Factor) from the causative agent, Bacillus anthracis. All the Anthrax vaccines currently in use or under development contain or produce PA, the major antigenic component of anthrax toxin, and there is a clear need for an improved vaccine for human use. In the previous report we described the first atomic resolution structure of PA, revealing that the molecule is composed largely of beta-sheets organized into four domains. This information can be usedmore » in the design. of recombinant PA vaccines. In this report we describe additional features of the full-length PA molecule derived from further crystallographic refinement and careful examination of the structure. We compare two crystal forms of PA grown at different pH values and discuss the functional implications. A complete definition of the function of each domain must await the crystal structure of the PA63 heptamer. We have grown crystals of the heptamer under both detergent and detergent-free conditions, and made substantial progress towards the crystal structure. The mechanism of anthrax intoxication in the light of our results is reviewed.« less

Potent antitumor activity of a urokinase-activated engineered anthrax toxin

NASA Astrophysics Data System (ADS)

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.

Letter from a Young Boy Following the "Panay" Incident

ERIC Educational Resources Information Center

Plante,Trevor K.; Potter, Lee Ann

2008-01-01

An attack by Japanese naval aircraft on the USS "Panay" in 1937, which the Japanese government declared accidental and for which it paid compensation, caused a crisis in U.S.-Japanese relations. A little-known dimension of the incident was the expression of spontaneous sympathy and apologies by Japanese citizens to the U.S. embassy in…

Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

PubMed

Wright, Jennifer Gordon; Quinn, Conrad P; Shadomy, Sean; Messonnier, Nancy

2010-07-23

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.

Detection and management of the first human anthrax outbreak in Togo.

PubMed

Patassi, Akouda Akessiwe; Saka, Bayaki; Landoh, Dadja Essoya; Agbenoko, Kodjo; Tamekloe, Tsidi; Salmon-Ceron, Dominique

2016-07-01

The aim of this study was to describe and define an outbreak of human anthrax in two villages in the northern savannah region of Togo. In December 2009, localised groups of deaths occurred among villagers and their livestock, confirmed to be due to anthrax at the district hospital of Dapaong in Northern Togo. The National Disease Control department undertook an investigation to describe the epidemiological, clinical and bacteriological characteristics of this outbreak. Thirty-four individuals presented with clinical manifestations of anthrax. All patients were known to have consumed meat from cattle who had died of unknown causes or had been killed as a result of unknown illness. All patients presented with muco-cutaneous lesions; some had gastro-intestinal, neurological or meningeal symptoms, or septicaemia. One patient was co-infected with Plasmodium falciparum. Six deaths (17.6%) were reported at the beginning of the epidemic; 28 patients were successfully treated with a 10-day course of intravenous Penicillin or oral Amoxicillin. The two factors that contributed to the ultimate resolution of the anthrax outbreak were the increase of community awareness toward health promotion and vaccination of all farm animals. Although six deaths occurred among families' members who were infected, new human anthrax cases were prevented by rapid treatment of victims as well as aggressive public health interventions. However the risk of re-emergence of infection and exposure still exists as there are no existing epidemiological mapping and no identification of infected zones; and furthermore, no functional anthrax surveillance system exists in the affected region. © The Author(s) 2015.

Mapping as a tool for predicting the risk of anthrax outbreaks in Northern Region of Ghana.

PubMed

Nsoh, Ayamdooh Evans; Kenu, Ernest; Forson, Eric Kofi; Afari, Edwin; Sackey, Samuel; Nyarko, Kofi Mensah; Yebuah, Nathaniel

2016-01-01

Anthrax is a febrile soil-born infectious disease that can affect all warm-blooded animals including man. Outbreaks of anthrax have been reported in northern region of Ghana but no concerted effort has been made to implement risk-based surveillance systems to document outbreaks so as to implement policies to address the disease. We generated predictive maps using soil pH, temperature and rainfall as predictor variables to identify hotspot areas for the outbreaks. A 10-year secondary data records on soil pH, temperature and rainfall were used to create climate-based risk maps using ArcGIS 10.2. The monthly mean values of rainfall and temperature for ten years were calculated and anthrax related evidence based constant raster values were created as weights for the three factors. All maps were generated using the Kriging interpolation method. There were 43 confirmed outbreaks. The deaths involved were 131 cattle, 44 sheep, 15 goats, 562 pigs with 6 human deaths and 22 developed cutaneous anthrax. We found three strata of well delineated distribution pattern indicating levels of risk due to suitability of area for anthrax spore survival. The likelihood of outbreaks occurrence and reoccurrence was higher in Strata I, Strata II and strata III respectively in descending order, due to the suitability of soil pH, temperature and rainfall for the survival and dispersal of B. anthracis spore. The eastern corridor of Northern region is a Hots spot area. Policy makers can develop risk based surveillance system and focus on this area to mitigate anthrax outbreaks and reoccurrence.

Changing livestock vaccination policy alters the epidemiology of human anthrax, Georgia, 2000-2013.

PubMed

Kracalik, Ian; Malania, Lile; Broladze, Mariam; Navdarashvili, Archil; Imnadze, Paata; Ryan, Sadie J; Blackburn, Jason K

2017-11-01

Anthrax is a widely spread zoonotic disease found on nearly every continent. To control the disease in humans and animals, annual livestock vaccination is recommended. However, in 2007, the country of Georgia ended its policy of compulsory annual livestock anthrax vaccination. Our objective was to assess how the epidemiology of human anthrax has evolved from 2000-2013 in Georgia, in the wake of this cessation. We used passive surveillance data on epidemiological surveys of human anthrax case patients. Risk factors and rates of self-reported sources of infection were compared, before and after the change in livestock vaccination policy. We mapped ethnicity-adjusted incidence during the two periods and assessed changes in the spatial pattern of risk. The overall risk of human anthrax increased >5-fold, from 0.7 cases per 100,000 in 2000 to 3.7 cases per 100,000 by 2013. Ethnic disparities in risk became pronounced; from 2000 to 2013, incidence increased >60-fold in Azerbaijanis from 0.35 to 21.1 cases/100,000 Azerbaijanis compared to 0.61 to 1.9 cases/100,000 among ethnic Georgians. Food-borne exposures from purchasing meat increased from 11% in 2000-2006 to 21% in 2007-2013. Spatial analyses revealed a shift from a random pattern of reporting pre-policy change to clustering among district municipalities following the change in policy. Our findings indicate there were unintended human health consequences associated with changing livestock vaccination policy. Following a reduction in the immunizations administered, there was a major shift in the epidemiology of human anthrax in Georgia. Current infection risk is now highest among ethnic minorities. Increased reporting among individuals uncharacteristically at risk for anthrax from foodborne exposures suggests spillover from modes of agricultural production. Given the importance of human-livestock health linkages, careful evaluations of policy need to be undertaken before changes to animal vaccination are made. Copyright © 2017 Elsevier Ltd. All rights reserved.

Practical limitation for continuous-variable quantum cryptography using coherent States.

PubMed

Namiki, Ryo; Hirano, Takuya

2004-03-19

In this Letter, first, we investigate the security of a continuous-variable quantum cryptographic scheme with a postselection process against individual beam splitting attack. It is shown that the scheme can be secure in the presence of the transmission loss owing to the postselection. Second, we provide a loss limit for continuous-variable quantum cryptography using coherent states taking into account excess Gaussian noise on quadrature distribution. Since the excess noise is reduced by the loss mechanism, a realistic intercept-resend attack which makes a Gaussian mixture of coherent states gives a loss limit in the presence of any excess Gaussian noise.

The roots of terrorism: A reassessment after September 11th

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilat, Joseph F.

2002-01-01

The brutal terrorist attacks of September 11th, the anthrax attacks that followed and growing knowledge of al Qaeda's pursuit of nuclear, biological and chemical weapons have not only intensified concerns about terrorism but also created doubts about our understanding of terrorism. These attacks were in many ways unprecedented, and ultimately raise the question of the roots or causes of terrorism. Historically and today, there have been divergent views on this question, which reflect philosophical, religious, political and other differences. These differences are not merely academic, as they can affect our understanding of both the threat and of responses to terrorismmore » in the aftermath of September 1 1 th. Terrorism is too complex and diverse a phenomenon to speak easily of causes. But we may be able to discern the causes of specific acts. Our response to 9/11 and other acts of terrorism will be affected by our understanding of their causes, as well as by possible political requirements to address widespread perceptions of causes. If 9/11 was caused by Islamic radicalism, the near-term response must be to ensure the terrorists are defeated and pose no fiuther danger. In the longer term, education is critical. If the attacks were caused by US Middle East policies, the response should involve a review of those policies. This may or may not result in changes to policy, public diplomacy, etc. If the attacks were a backlash against globalization, the response must address the realities underlying anti-globalization sentiments. Addressing causes (real and perceived) will not in any case end terrorism, and addressing the wrong causes can be counterproductive. Actions to reduce those conditions that create support for terrorism and aid its recruitment effort are critical to any counterterrorism strategy. For this reason alone, we must do everything possible to understand the reasons terrorism may be undertaken, including the attacks of September 1 1 th. This paper will look at the question of the roots of terrorism and then look to the specific case of 9/11 and its aftermath, with a special view to the impact of globalization.« less

Anthrax Vaccines: Pasteur to the Present

DTIC Science & Technology

2006-01-01

pathogenesis Anthrax is most often a disease of ruminants that can afflict a wide variety of mammals, including humans. Three forms of the disease are...91 Sloat, B. R. and Cui , Z. (2005) Strong mucosal and systemic immunities induced by nasal immunization with anthrax pro- tective antigen protein...strains with variant plasmid contents . Infect. Immun. 73, 3646–3658. 115 Wang, J., Ying, T., Wang, H., Shi, Z., Li, M., He, K., Feng, E., Wang, J

A synthetic peptide vaccine directed against the 2ß2-2ß3 loop of domain 2 of protective antigen protects rabbits from inhalation anthrax.

PubMed

Oscherwitz, Jon; Yu, Fen; Cease, Kemp B

2010-09-15

The current vaccines for anthrax in the United States and United Kingdom are efficacious in the two most accepted animal models of inhalation anthrax, nonhuman primates and rabbits, but require extensive immunization protocols. We previously demonstrated that a linear determinant in domain 2 of Bacillus anthracis protective Ag (PA) is a potentially important target for an epitope-specific vaccine for anthrax, as Abs specific for this site, referred to as the loop-neutralizing determinant (LND), neutralize lethal toxin in vitro, yet are virtually absent in PA-immunized rabbits. In this study, we evaluated the immunogenicity and protective efficacy in rabbits of multiple antigenic peptides (MAPs) consisting of aa 304-319 from the LND of PA colinearly synthesized at the C terminus (T-B MAP) or N terminus (B-T MAP) with a heterologous T cell epitope from Plasmodium falciparum. Immunogenicity studies demonstrated that both MAPs elicited toxin-neutralizing Ab in rabbits. To evaluate the MAPs as potential anthrax vaccines, we immunized groups of rabbits (n = 7) with each MAP in Freund's adjuvant and then exposed all rabbits to a 200-LD(50) challenge with aerosolized spores of B. anthracis Ames strain. All seven rabbits immunized with the B-T MAP and 89% (six of seven) of rabbits immunized with the T-B MAP survived the spore challenge. Corollary studies with reference sera from human vaccinees immunized with rPA or anthrax vaccine absorbed and nonhuman primates immunized with PA revealed no detectable Ab with specificity for the LND. We conclude that a synthetic peptide vaccine targeting the LND would be a potentially efficacious vaccine for anthrax.

Analysis of the Fc Gamma Receptor-Dependent Component of Neutralization Measured by Anthrax Toxin Neutralization Assays▿

PubMed Central

Verma, Anita; Ngundi, Miriam M.; Meade, Bruce D.; De Pascalis, Roberto; Elkins, Karen L.; Burns, Drusilla L.

2009-01-01

Anthrax toxin neutralization assays are used to measure functional antibody levels elicited by anthrax vaccines in both preclinical and clinical studies. In this study, we investigated the magnitude and molecular nature of Fc gamma (Fcγ) receptor-dependent toxin neutralization observed in commonly used forms of the anthrax toxin neutralization assay. Significantly more Fcγ receptor-dependent neutralization was observed in the J774A.1 cell-based assay than in the RAW 264.7 cell-based assay, a finding that could be due to the larger numbers of Fcγ receptors that we found on J774A.1 cells by using flow cytometry. Thus, the extent to which Fcγ receptor-dependent neutralization contributes to the total neutralization measured by the assay depends on the specific cell type utilized in the assay. Using Fcγ receptor blocking monoclonal antibodies, we found that at least three murine Fcγ receptor classes, IIB, III, and IV, can contribute to Fcγ receptor-dependent neutralization. When antibodies elicited by immunization of rabbits with protective-antigen-based anthrax vaccines were analyzed, we found that the magnitude of Fcγ receptor-dependent neutralization observed in the J774A.1 cell-based assay was dependent on the concentration of protective antigen utilized in the assay. Our results suggest that the characteristics of the antibodies analyzed in the assay (e.g., species of origin, isotype, and subclass), as well as the assay design (e.g., cell type and protective antigen concentration), could significantly influence the extent to which Fcγ receptor-dependent neutralization contributes to the total neutralization measured by anthrax toxin neutralization assays. These findings should be considered when interpreting anthrax toxin neutralization assay output. PMID:19656993

[Screening of full human anthrax lethal factor neutralizing antibody in transgenic mice].

PubMed

Wang, Xiaolin; Chi, Xiangyang; Liu, Ju; Liu, Weicen; Liu, Shuling; Qiu, Shunfang; Wen, Zhonghua; Fan, Pengfei; Liu, Kun; Song, Xiaohong; Fu, Ling; Zhang, Jun; Yu, Changming

2016-11-25

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

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

PubMed

Parlak, Emine; Parlak, Mehmet

2016-01-01

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

Combination of Two Candidate Subunit Vaccine Antigens Elicits Protective Immunity to Ricin and Anthrax Toxin in Mice

PubMed Central

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

2014-01-01

In an effort to develop combination vaccines for biodefense, we evaluated a ricin subunit antigen, RiVax, given in conjunction with an anthrax protective antigen, DNI. The combination led to high endpoint titer antibody response, neutralizing antibodies, and protective immunity against ricin and anthrax lethal toxin. This is a natural combination vaccine, since both antigens are recombinant subunit proteins that would be given to the same target population. PMID:25475957

Immunization Against Potential Biological Warfare Agents

DTIC Science & Technology

2000-06-01

Human live anthrax vaccine in the former USSR. Vaccine 1994; 12:727-30. 11. Stanley JL, Smith H . Purification of factor I and recognition of a...third factor of the anthrax toxin. J Gen Microbiol 1961;26:49-66. 12. Stanley JL, Smith H . The three factors of anthrax toxin: their immunogenicity...vaccination. In: Madkour MM, ed. Bru- cellosis. Madkour MM, ed. London: Butterworths, 1989:263-9. 40. Roux J. Brucella vaccines in humans. In: Madkour MM, ed

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

PubMed Central

Sun, Der-Shan; Kau, Jyh-Hwa; Huang, Hsin-Hsien; Tseng, Yao-Hsuan; Wu, Wen-Shiang; Chang, Hsin-Hou

2016-01-01

The bactericidal activity of conventional titanium dioxide (TiO2) photocatalyst is effective only on irradiation by ultraviolet light, which restricts the applications of TiO2 for use in living environments. Recently, carbon-containing TiO2 nanoparticles [TiO2(C) NP] were found to be a visible-light-responsive photocatalyst (VLRP), which displayed significantly enhanced antibacterial properties under visible light illumination. However, whether TiO2(C) NPs exert antibacterial properties against Bacillus anthracis remains elusive. Here, we evaluated these VLRP NPs in the reduction of anthrax-induced pathogenesis. Bacteria-killing experiments indicated that a significantly higher proportion (40%–60%) of all tested Bacillus species, including B. subtilis, B. cereus, B. thuringiensis, and B. anthracis, were considerably eliminated by TiO2(C) NPs. Toxin inactivation analysis further suggested that the TiO2(C) NPs efficiently detoxify approximately 90% of tested anthrax lethal toxin, a major virulence factor of anthrax. Notably, macrophage clearance experiments further suggested that, even under suboptimal conditions without considerable bacterial killing, the TiO2(C) NP-mediated photocatalysis still exhibited antibacterial properties through the reduction of bacterial resistance against macrophage killing. Our results collectively suggested that TiO2(C) NP is a conceptually feasible anti-anthrax material, and the relevant technologies described herein may be useful in the development of new strategies against anthrax. PMID:28335365

Neutralizing antibody and functional mapping of Bacillus anthracis protective antigen-The first step toward a rationally designed anthrax vaccine.

PubMed

McComb, Ryan C; Martchenko, Mikhail

2016-01-02

Anthrax is defined by the Centers for Disease Control and Prevention as a Category A pathogen for its potential use as a bioweapon. Current prevention treatments include Anthrax Vaccine Adsorbed (AVA). AVA is an undefined formulation of Bacillus anthracis culture supernatant adsorbed to aluminum hydroxide. It has an onerous vaccination schedule, is slow and cumbersome to produce and is slightly reactogenic. Next-generation vaccines are focused on producing recombinant forms of anthrax toxin in a well-defined formulation but these vaccines have been shown to lose potency as they are stored. In addition, studies have shown that a proportion of the antibody response against these vaccines is focused on non-functional, non-neutralizing regions of the anthrax toxin while some essential functional regions are shielded from eliciting an antibody response. Rational vaccinology is a developing field that focuses on designing vaccine antigens based on structural information provided by neutralizing antibody epitope mapping, crystal structure analysis, and functional mapping through amino acid mutations. This information provides an opportunity to design antigens that target only functionally important and conserved regions of a pathogen in order to make a more optimal vaccine product. This review provides an overview of the literature related to functional and neutralizing antibody epitope mapping of the Protective Antigen (PA) component of anthrax toxin. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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 biosensor, protective antigen ion channel asymmetric blockade.

PubMed

Halverson, Kelly M; Panchal, Rekha G; Nguyen, Tam L; Gussio, Rick; Little, Stephen F; Misakian, Martin; Bavari, Sina; Kasianowicz, John J

2005-10-07

The significant threat posed by biological agents (e.g. anthrax, tetanus, botulinum, and diphtheria toxins) (Inglesby, T. V., O'Toole, T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Friedlander, A. M., Gerberding, J., Hauer, J., Hughes, J., McDade, J., Osterholm, M. T., Parker, G., Perl, T. M., Russell, P. K., and Tonat, K. (2002) J. Am. Med. Assoc. 287, 2236-2252) requires innovative technologies and approaches to understand the mechanisms of toxin action and to develop better therapies. Anthrax toxins are formed from three proteins secreted by fully virulent Bacillus anthracis, protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). Here we present electrophysiological measurements demonstrating that full-length LF and EF convert the current-voltage relationship of the heptameric PA63 ion channel from slightly nonlinear to highly rectifying and diode-like at pH 6.6. This effect provides a novel method for characterizing functional toxin interactions. The method confirms that a previously well characterized PA63 monoclonal antibody, which neutralizes anthrax lethal toxin in animals in vivo and in vitro, prevents the binding of LF to the PA63 pore. The technique can also detect the presence of anthrax lethal toxin complex from plasma of infected animals. The latter two results suggest the potential application of PA63 nanopore-based biosensors in anthrax therapeutics and diagnostics.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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

2015-04-01

Inhalational anthrax is characterized by extensive bacteremia and toxemia as well as nonspecific to mild flu-like symptoms, until the onset of hypotension, shock, and mortality. Without treatment, the mortality rate approaches 100%. Antibiotic treatment is not always effective, and alternative treatments are needed, such as monotherapy for antibiotic-resistant inhalational anthrax or as an adjunct therapy in combination with antibiotics. The Bacillus anthracis antitoxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric deimmunized antibody which targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective efficacy of the adjunct therapy with the MAb. Following detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the efficacy of the combination adjunct therapy with that of an antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicate that a subtherapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in nonvaccinated individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

2014 Anthrax epidemic in Koubia prefecture, Guinea-Conakry.

PubMed

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.

Cryo-electron microscopy study of bacteriophage T4 displaying anthrax toxin proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fokine, Andrei; Bowman, Valorie D.; Battisti, Anthony J.

2007-10-25

The bacteriophage T4 capsid contains two accessory surface proteins, the small outer capsid protein (Soc, 870 copies) and the highly antigenic outer capsid protein (Hoc, 155 copies). As these are dispensable for capsid formation, they can be used for displaying proteins and macromolecular complexes on the T4 capsid surface. Anthrax toxin components were attached to the T4 capsid as a fusion protein of the N-terminal domain of the anthrax lethal factor (LFn) with Soc. The LFn-Soc fusion protein was complexed in vitro with Hoc{sup -}Soc{sup -}T4 phage. Subsequently, cleaved anthrax protective antigen heptamers (PA63){sub 7} were attached to the exposedmore » LFn domains. A cryo-electron microscopy study of the decorated T4 particles shows the complex of PA63 heptamers with LFn-Soc on the phage surface. Although the cryo-electron microscopy reconstruction is unable to differentiate on its own between different proposed models of the anthrax toxin, the density is consistent with a model that had predicted the orientation and position of three LFn molecules bound to one PA63 heptamer.« less

Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.

PubMed

Klinman, Dennis M; Yamamoto, Masaki; Tross, Debra; Tomaru, Koji

2009-12-01

The intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. While individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. Concern over the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax vaccines based on purified recombinant protective antigen (rPA) have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents. Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants. Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy.

Immunological and functional comparison between Clostridium perfringens iota toxin, C. spiroforme toxin, and anthrax toxins.

PubMed

Perelle, S; Scalzo, S; Kochi, S; Mock, M; Popoff, M R

1997-01-01

Clostridium perfringens iota and C. spiroforme toxins consist of two separate proteins. One is the binding component and the other the enzymatic component. The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen, lethal factor, and edema factor. As shown by Western blotting and ELISA, the binding component of anthrax toxin shares common epitopes with that of iota toxin and C. spiroforme toxin which are closely related immunologically. However, no functional complementation was observed between iota toxin and anthrax toxin components. The binding components can form toxins active on macrophages only in combination with their respective enzymatic components. Agents which prevent acidification of endosomes do not have the same effects on anthrax toxin activity as they do on iota and C. spiroforme toxins. Therefore, the mechanisms of entry into the cells are presumably different. Since the binding components of anthrax toxins and iota toxin share a conserved putative translocation domain, these binding components could have a common mode of insertion into the cell membranes.

Growth medium for the rapid isolation and identification of anthrax

NASA Astrophysics Data System (ADS)

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).

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gkazonis, Petros V.; Dalkas, Georgios A.; Chasapis, Christos T.

2010-06-04

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

The Application of the Haddon Matrix to Public Health Readiness and Response Planning

PubMed Central

Barnett, Daniel J.; Balicer, Ran D.; Blodgett, David; Fews, Ayanna L.; Parker, Cindy L.; Links, Jonathan M.

2005-01-01

State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public’s health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. Public health readiness and response activities can be conceptualized similarly for intentional attacks, natural disasters, and human-caused accidents. Consistent with this view, the federal government has adopted the all-hazards response model as its fundamental paradigm. Adoption of this paradigm provides powerful improvements in efficiency and efficacy, because it reduces the need to create a complex family of situation-specific preparedness and response activities. However, in practice, public health preparedness requires additional models and tools to provide a framework to better understand and prioritize emergency readiness and response needs, as well as to facilitate solutions; this is particularly true at the local health department level. Here, we propose to extend the use of the Haddon matrix—a conceptual model used for more than two decades in injury prevention and response strategies—for this purpose. PMID:15866764

Disaster preparedness, pediatric considerations in primary blast injury, chemical, and biological terrorism

PubMed Central

Hamele, Mitchell; Poss, William Bradley; Sweney, Jill

2014-01-01

Both domestic and foreign terror incidents are an unfortunate outgrowth of our modern times from the Oklahoma City bombings, Sarin gas attacks in Japan, the Madrid train bombing, anthrax spores in the mail, to the World Trade Center on September 11th, 2001. The modalities used to perpetrate these terrorist acts range from conventional weapons to high explosives, chemical weapons, and biological weapons all of which have been used in the recent past. While these weapons platforms can cause significant injury requiring critical care the mechanism of injury, pathophysiology and treatment of these injuries are unfamiliar to many critical care providers. Additionally the pediatric population is particularly vulnerable to these types of attacks. In the event of a mass casualty incident both adult and pediatric critical care practitioners will likely be called upon to care for children and adults alike. We will review the presentation, pathophysiology, and treatment of victims of blast injury, chemical weapons, and biological weapons. The focus will be on those injuries not commonly encountered in critical care practice, primary blast injuries, category A pathogens likely to be used in terrorist incidents, and chemical weapons including nerve agents, vesicants, pulmonary agents, cyanide, and riot control agents with special attention paid to pediatric specific considerations. PMID:24834398

Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

PubMed Central

Ngundi, Miriam M.; Meade, Bruce D.; Little, Stephen F.; Quinn, Conrad P.; Corbett, Cindi R.; Brady, Rebecca A.

2012-01-01

Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax. PMID:22441391

Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques.

PubMed

Livingston, Brian D; Little, Stephen F; Luxembourg, Alain; Ellefsen, Barry; Hannaman, Drew

2010-01-22

DNA vaccination is a promising immunization strategy that could be applied in the development of vaccines for a variety of prophylactic and therapeutic indications. Utilizing anthrax protective antigen as a model antigen, we demonstrate that electroporation mediated delivery enhanced the immunogenicity of DNA vaccines in nonhuman primates over 100-fold as compared to conventional intramuscular injection. Two administrations of a DNA vaccine with electroporation elicited anthrax toxin neutralizing antibody responses in 100% of rhesus macaques. Toxin neutralizing antibodies were sustained for the nearly 1-year study duration and were correlated with protection against subsequent lethal Bacillus anthracis spore challenge. Collectively, electroporation mediated DNA vaccination conferred protection comparable to that observed following vaccination with an FDA approved anthrax vaccine.

Anthrax of domestic animals in Vrbas Banate: from traditional beliefs to the first scientific views on the ancient disease.

PubMed

Stevanović, Oliver N; Nedić, Drago N; Šubarević, Nemanja; Tomić, Obren

2016-12-01

From 1929 to 1941, the Vrbas Banate was one of nine provinces of the Kingdom Yugoslavia, and according to historical data, the poorest one, without well-organized and sustainable agriculture production. Naturalistic production and poor animal health control in the Vrbas Banate were the most important risk factors for infectious disease spreading. Anthrax was very prevalent infectious disease in domestic animals and humans in that period, but some data on this disease remain scarce. In this paper epidemiology and clinical investigation of anthrax in the Vrbas Banate are reviewed. Apart from many aggravating factors that influenced the control of anthrax, the veterinary service of Banate contributed to the development of animal husbandry, animal health and public health in that period.

List of Contractors to Support Anthrax Remediation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Judd, Kathleen S.; Lesperance, Ann M.

2010-05-14

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

Pandemic influenza planning, United States, 1978-2008.

PubMed

Iskander, John; Strikas, Raymond A; Gensheimer, Kathleen F; Cox, Nancy J; Redd, Stephen C

2013-06-01

During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community's response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.

Public health and national security: the critical role of increased federal support.

PubMed

Frist, Bill

2002-01-01

Protecting the public's health historically has been a state and local responsibility. However, the growing threat of bioterrorism has highlighted the importance of a strong public health infrastructure to the nation's homeland security and has focused increased attention on the preparedness of the public health system. As a result, federal public health funding has increased exponentially since the anthrax attacks of late 2001, and Congress has passed sweeping new federal legislation intended to strengthen the nation's public health system. This heightened level of federal interest and support should yield important public health benefits. Most recognize that after years of neglect the public health infrastructure cannot be rebuilt overnight. As we implement a comprehensive strategy to increase the capabilities and capacity of our nation's public health system, it is essential to address a series of important policy questions, including the appropriate level of ongoing public health investments from local, state, and federal sources.

Medical toxicology and public health-update on research and activities at the centers for disease control and prevention and the agency for toxic substances and disease registry.

PubMed

Snook, Curtis P; Cardarelli, John; Mickelsen, R Leroy; Mattorano, Dino; Nalipinski, Michael

2008-12-01

An extensive review of CDC epidemiological responses to human outbreaks of anthrax from occupational settings between the years of 1950 and 2001 documented a variety of approaches to mitigation and decontamination [2]. These approaches included taking no action, burning contaminated materials, chlorinating water supplies, instituting administrative and engineering controls and PPE, vaccinating potentially exposed individuals, and in 2 instances, fumigating with formaldehyde vapor (now considered to be a human carcinogen). Secondary contamination of a worker's home was documented in 1 case, but not felt to be clinically significant to warrant any decontamination efforts. In response to the B. anthracis attacks in 2001, chlorine dioxide fumigation, vaporous hydrogen peroxide fumigation, and a combination of HEPA vacuuming, cleaning, and bleach application were all techniques used successfully to clean B. anthracis spore contamination.

Agility in adversity: Vaccines on Demand.

PubMed

De Groot, Anne S; Moise, Leonard; Olive, David; Einck, Leo; Martin, William

2016-09-01

Is the US ready for a biological attack using Ebola virus or Anthrax? Will vaccine developers be able to produce a Zika virus vaccine, before the epidemic spreads around the world? A recent report by The Blue Ribbon Study Panel on Biodefense argues that the US is not ready for these challenges, however, technologies and capabilities that could address these deficiencies are within reach. Vaccine technologies have advanced and readiness has improved in recent years, due to advances in sequencing technology and computational power making the 'vaccines on demand' concept a reality. Building a robust strategy to design effective biodefense vaccines from genome sequences harvested by real-time biosurveillance will benefit from technologies that are being brought to bear on the cancer cure 'moonshot'. When combined with flexible vaccine production platforms, vaccines on demand will relegate expensive and, in some cases, insufficiently effective vaccine stockpiles to the dust heap of history.

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

PubMed

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

2015-01-09

In an effort to develop combination vaccines for biodefense, we evaluated a ricin subunit antigen, RiVax, given in conjunction with an anthrax protective antigen, DNI. The combination led to high endpoint titer antibody response, neutralizing antibodies, and protective immunity against ricin and anthrax lethal toxin. This is a natural combination vaccine, since both antigens are recombinant subunit proteins that would be given to the same target population. Copyright © 2014 Elsevier Ltd. All rights reserved.

75 FR 66085 - Agency Information Collection Activities; Proposed Collection; Comment Request; Certification of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... comply with the terms and conditions of the pesticide registration (e.g., registrants of anthrax-related pesticide products that assert claims to inactivate bacillus anthracis (anthrax) spores). Paperwork...

Cutaneous anthrax associated with drum making using goat hides from West Africa--Connecticut, 2007.

PubMed

2008-06-13

On August 29, 2007, the Connecticut Department of Public Health was notified by a physician of suspect cutaneous anthrax involving a drum maker and one of his three children. The drum maker had been working with untreated goat hides from Guinea in West Africa. This report summarizes results of the joint epidemiologic and environmental investigation conducted by public health officials, environmental agencies, and law enforcement authorities. The investigation revealed that the drum maker was exposed while working with a contaminated goat hide from Guinea and that his workplace and home were contaminated with anthrax. His child was most likely exposed from cross-contamination of the home. The findings underscore the potential hazard of working with untreated animal hides from areas with epizootic anthrax and the potential for secondary cases from environmental contamination.

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

PubMed

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.

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

PubMed Central

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

2013-01-01

An intense effort has been launched to develop improved anthrax vaccines that confer rapid, long lasting protection preferably with an extended stability profile amenable for stockpiling. Protective antigen (PA)-based vaccines are most favored as immune responses directed against PA are singularly protective, although the actual protective mechanism remains to be unraveled. Herein we show that contrary to the prevailing view, an efficacious PA-based vaccine confers protection against inhalation anthrax by preventing the establishment of a toxin-releasing systemic infection. Equally importantly, antibodies measured by the in vitro lethal toxin neutralization activity assay (TNA) that is considered as a reliable correlate of protection, especially for PA protein-based vaccines adjuvanted with aluminum salts appear to be not absolutely essential for this protective immune response. PMID:23787486

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

PubMed

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

2013-09-01

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

[The experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated against plague and anthrax].

PubMed

Bogacheva, N V; Kriuchkov, A V; Darmov, I V; Vorob'ev, K A; Pechenkin, D V; Elagin, G D; Kolesnikiov, D P

2013-11-01

The article deals with experimental evaluation with flow cytofluorimetry technique of the level of cellular immunologic memory in persons vaccinated with plague and anthrax live dry vaccines. It is established that the introduction of plague and anthrax live dry vaccines into organism of vaccinated persons ignites immunologic rearrangement manifested by reliable increase of level of blood concentration of Th1-lymphocytes (immunologic memory cells) against the background of vaccination. The higher correlation coefficient is detected between leucocytes lysis coefficient and stimulation coefficient according blood concentration level of T-lymphocytes predominantly at the expense of Th1-lymphocytes. The values of stimulation coefficient were calculated for corresponding blood cells of vaccinated persons. This data testifies the effectiveness of application of vaccination against plague and anthrax.

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

NASA Astrophysics Data System (ADS)

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

2009-05-01

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

Killed but metabolically active Bacillus anthracis vaccines induce broad and protective immunity against anthrax.

PubMed

Skoble, Justin; Beaber, John W; Gao, Yi; Lovchik, Julie A; Sower, Laurie E; Liu, Weiqun; Luckett, William; Peterson, Johnny W; Calendar, Richard; Portnoy, Daniel A; Lyons, C Rick; Dubensky, Thomas W

2009-04-01

Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting the spoIIE and uvrAB genes, rendering B. anthracis extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into the lef and cya genes, which allowed inactive but immunogenic toxins to be produced. Photochemically inactivated vaccine strains maintained a high degree of metabolic activity and secreted protective antigen (PA), lethal factor, and edema factor. KBMA B. anthracis vaccines were avirulent in mice and induced less injection site inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMA B. anthracis-vaccinated animals produced antibodies against numerous anthrax antigens, including high levels of anti-PA and toxin-neutralizing antibodies. Vaccination with KBMA B. anthracis fully protected mice against challenge with lethal doses of toxinogenic unencapsulated Sterne 7702 spores and rabbits against challenge with lethal pneumonic doses of fully virulent Ames strain spores. Guinea pigs vaccinated with KBMA B. anthracis were partially protected against lethal Ames spore challenge, which was comparable to vaccination with the licensed vaccine anthrax vaccine adsorbed. These data demonstrate that KBMA anthrax vaccines are well tolerated and elicit potent protective immune responses. The use of KBMA vaccines may be broadly applicable to bacterial pathogens, especially those for which the correlates of protective immunity are unknown.

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

PubMed

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

2014-11-01

In the past decade, several Bacillus cereus strains have been isolated from otherwise healthy individuals who succumbed to bacterial pneumonia presenting symptoms resembling inhalational anthrax. One strain was indistinguishable from B. cereus G9241, previously cultured from an individual who survived a similar pneumonia-like illness and which was shown to possess a complete set of plasmid-borne anthrax toxin-encoding homologs. The finding that B. cereus G9241 pathogenesis in mice is dependent on pagA1-derived protective antigen (PA) synthesis suggests that an anthrax toxin-based vaccine may be effective against this toxin-encoding B. cereus strain. Dunkin Hartley guinea pigs were immunized with protein- and DNA-based anthrax toxin-based vaccines, immune responses were evaluated and survival rates were calculated after lethal aerosol exposure with B. cereus G9241 spores. Each vaccine induced seroconversion with the protein immunization regimen eliciting significantly higher serum levels of antigen-specific antibodies at the prechallenge time-point compared with the DNA-protein prime-boost immunization schedule. Complete protection against lethal challenge was observed in all groups with a detectable prechallenge serum titer of toxin neutralizing antibodies. For the first time, we demonstrated that the efficacy of fully defined anthrax toxin-based vaccines was protective against lethal B. cereus G9241 aerosol challenge in the guinea pig animal model. Published 2014. This article is a US Government work and is in the public domain in the USA.

Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

PubMed Central

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

2014-01-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

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

PubMed

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

2014-04-01

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

Genetic source tracking of an anthrax outbreak in Shaanxi province, China.

PubMed

Liu, Dong-Li; Wei, Jian-Chun; Chen, Qiu-Lan; Guo, Xue-Jun; Zhang, En-Min; He, Li; Liang, Xu-Dong; Ma, Guo-Zhu; Zhou, Ti-Cao; Yin, Wen-Wu; Liu, Wei; Liu, Kai; Shi, Yi; Ji, Jian-Jun; Zhang, Hui-Juan; Ma, Lin; Zhang, Fa-Xin; Zhang, Zhi-Kai; Zhou, Hang; Yu, Hong-Jie; Kan, Biao; Xu, Jian-Guo; Liu, Feng; Li, Wei

2017-01-17

Anthrax is an acute zoonotic infectious disease caused by the bacterium known as Bacillus anthracis. From 26 July to 8 August 2015, an outbreak with 20 suspected cutaneous anthrax cases was reported in Ganquan County, Shaanxi province in China. The genetic source tracking analysis of the anthrax outbreak was performed by molecular epidemiological methods in this study. Three molecular typing methods, namely canonical single nucleotide polymorphisms (canSNP), multiple-locus variable-number tandem repeat analysis (MLVA), and single nucleotide repeat (SNR) analysis, were used to investigate the possible source of transmission and identify the genetic relationship among the strains isolated from human cases and diseased animals during the outbreak. Five strains isolated from diseased mules were clustered together with patients' isolates using canSNP typing and MLVA. The causative B. anthracis lineages in this outbreak belonged to the A.Br.001/002 canSNP subgroup and the MLVA15-31 genotype (the 31 genotype in MLVA15 scheme). Because nine isolates from another four provinces in China were clustered together with outbreak-related strains by the canSNP (A.Br.001/002 subgroup) and MLVA15 method (MLVA15-31 genotype), still another SNR analysis (CL10, CL12, CL33, and CL35) was used to source track the outbreak, and the results suggesting that these patients in the anthrax outbreak were probably infected by the same pathogen clone. It was deduced that the anthrax outbreak occurred in Shaanxi province, China in 2015 was a local occurrence.

ANTHRAX IN THE MACKENZIE WOOD BISON (BISON BISON ATHABASCAE) POPULATION: 2012 ANTHRAX OUTBREAK AND HISTORICAL EXPOSURE IN NONOUTBREAK YEARS.

PubMed

New, Dallas; Elkin, Brett; Armstrong, Terry; Epp, Tasha

2017-10-01

Anthrax, caused by the spore-forming bacterium Bacillus anthracis, poses a threat to wood bison (Bison bison athabascae) conservation. We used descriptive epidemiology to characterize a large outbreak of anthrax in the Mackenzie bison population in the Northwest Territories, Canada, in 2012 and investigated historical serologic exposure of the bison to the bacterium in nonoutbreak years. Between late June and early August 2012, 451 bison carcasses were detected; mortality peaked from 13-19 July. A substantial number of calves, yearlings, and adult females died in the 2012 outbreak, unlike in two previous anthrax outbreaks in this population that killed mostly mature males. On the basis of the difference in estimates of population size prior to the outbreak (2012) and after the outbreak (2013), it is possible that not all dead bison were found during the outbreak. We assessed serologic history of exposure to B. anthracis by using samples from the Mackenzie wood bison population collected between 1986 and 2009. Overall, 87 of 278 samples were positive (31%). Seroprevalence was lower in females (18%, 10/55) than males (36%, 72/203). The highest proportion of positive submissions (90%) was from 1994, the year following the only anthrax outbreak within the historical data set. Both adult males and females had a higher likelihood of being seropositive than the younger age categories. There was a trend toward declining antibody levels between the 1993 and 2012 outbreak years.

The letters of Alix Joffroy (1844-1908), a medical intern at Lariboisière's Hospital at the time of the Commune of Paris.

PubMed

Tiberghien, Denis

2016-02-01

Since opening in 1848, Lariboisière's Hospital was strongly associated with the history of Paris and especially with the terrible days of the siege of Paris and the fights of the Commune. On the day after the surrender, Alix Joffroy wrote his first letter to his mother. He described the events as he experienced them, expressing his feelings about the causes of this political and military disaster and his experience there as an intern. Some weeks after the defeat of France by the Prussians, humbled Parisians attacked governmental troops. From March to May 1871 an improvised insurrectionary movement, The Commune of Paris, had taken power in the capital During the Bloody Week from 21 to 28 May 1871; this movement was suppressed by the Versaillaise Army. In his second letter, Joffroy related with great realism the tooth and nail fighting at the barricades and then the savage repression by the Army of the Communards around Lariboisière's Hospital. Two letters preciously preserved by Alix Joffroy's descendants give this man's unique direct account of a tragic period of the 19th century. © The Author(s) 2014.

Anthrax Vaccine

MedlinePlus

... products some military personnel, as determined by the Department of Defense These people should get five doses of vaccine ( ... cdc.gov/agent/anthrax/vaccination/. Contact the U.S Department of Defense (DoD): call 1-877-438-8222 or visit ...

Anthrax

MedlinePlus

... in humans — although it's very rare. In the environment, the anthrax-causing bacterium forms spores (a version of the germ covered by a hard protective shell) that can live in the soil for years. People can become infected by coming ...

Dominant-Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax

NASA Astrophysics Data System (ADS)

Sellman, Bret R.; Mourez, Michael; John Collier, R.

2001-04-01

The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.

Historical cases of anthrax in Sweden 1916-1961.

PubMed

Elvander, M; Persson, B; Sternberg Lewerin, S

2017-06-01

As in most European countries, anthrax was common in Swedish livestock during the centuries leading up to the mid-twentieth century. After 1957, the disease was regarded as practically extinct. However, in the past 7 years, three outbreaks have caused public alarm because of the risk of environmental contamination. Properly buried carcasses should present little risk of spore contamination, and instructions were in place to ensure this since the 1890s. However, as has been demonstrated in recent outbreaks, carcasses were not always adequately buried and viable spores may remain in some sites. This study was prompted by the lack of historical information to assess the geographical risk of old anthrax spores. The aim was to obtain sufficient information to map old anthrax outbreaks, to study clusters and variation between years. Historical data were retrieved from Official National and Regional Veterinary Archives. In the years 1916 to 1961, anthrax was reported from more than 3000 farms and all 24 counties in Sweden were affected. Most cases were single animals, but there were also some larger outbreaks mainly involving cattle. Anthrax in horses was mostly reported before the mid-twentieth century, and the same was seen for pigs and wildlife. A ban in 1957, on the import of bone meal for animal feed led to a drastic reduction of outbreaks. The majority of cases were reported during the summer months in animals on pasture. Historical records proved useful for the investigation of current outbreaks. If handled properly, old carcasses pose no substantial risk, but if not, they may present a risk to grazing animals in some areas. Historical information is useful for all planning of work that involves digging or relocation of soil masses. Anthrax can be regarded as one of the diseases where history is a key to present knowledge. © 2015 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POST... medical officer. (As a precautionary measure, all persons exposed to anthrax infection should report...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POST... medical officer. (As a precautionary measure, all persons exposed to anthrax infection should report...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POST... medical officer. (As a precautionary measure, all persons exposed to anthrax infection should report...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION POST... medical officer. (As a precautionary measure, all persons exposed to anthrax infection should report...

ANTHRAX REMEDIATION RESEARCH NEEDS

EPA Science Inventory

The Environmental Protection Agency has initiated a research program to respond to the immediate needs arising from the recent Bacillus anthracis bioterrorism events. Although the program has a strong emphasis on anthrax, other pathogens and chemical agents, including toxic indu...

9 CFR 95.9 - Glue stock; requirements for unrestricted entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... such materials have been removed from animals found at time of slaughter to be free from anthrax, foot... such specified abattoir and found free from anthrax foot-and-mouth disease, and rinderpest. 4 See...

9 CFR 95.9 - Glue stock; requirements for unrestricted entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... such materials have been removed from animals found at time of slaughter to be free from anthrax, foot... such specified abattoir and found free from anthrax foot-and-mouth disease, and rinderpest. 4 See...

Adherence to Antimicrobial Inhalational Anthrax Prophylaxis among Postal Workers, Washington, D.C., 2001

PubMed Central

Laserson, Kayla; Fry, Alicia M.; Roy, Sharon; Hayslett, James; Grummer-Strawn, Laurence; Kettel-Khan, Laura; Schuchat, Anne

2002-01-01

In October 2001, two envelopes containing Bacillus anthracis spores were processed at the Washington, D.C., Processing and Distribution Center of the U.S. Postal Service; inhalational anthrax developed in four workers at this facility. More than 2,000 workers were advised to complete 60 days of postexposure prophylaxis to prevent inhalational anthrax. Interventions to promote adherence were carried out to support workers, and qualitative information was collected to evaluate our interventions. A quantitative survey was administered to a convenience sample of workers to assess factors influencing adherence. No anthrax infections developed in any workers involved in the interventions or interviews. Of 245 workers, 98 (40%) reported full adherence to prophylaxis, and 45 (18%) had completely discontinued it. Experiencing adverse effects to prophylaxis, anxiety, and being <45 years old were risk factors for discontinuing prophylaxis. Interventions, especially frequent visits by public health staff, proved effective in supporting adherence. PMID:12396929

Anthrax and the geochemistry of soils in the contiguous United States

USGS Publications Warehouse

Griffin, Dale W.; Silvestri, Erin E.; Bowling, Charlena Y.; Boe, Timothy; Smith, David B.; Nichols, Tonya L.

2014-01-01

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.

Epidemiologic Responses to Anthrax Outbreaks: A Review of Field Investigations, 1950–2001

PubMed Central

Bales, Michael E.; Brachman, Philip S.; Kaufmann, Arnold F.; Klatsky, Peter C.; Ashford, David A.

2002-01-01

We used unpublished reports, published manuscripts, and communication with investigators to identify and summarize 49 anthrax-related epidemiologic field investigations conducted by the Centers for Disease Control and Prevention from 1950 to August 2001. Of 41 investigations in which Bacillus anthracis caused human or animal disease, 24 were in agricultural settings, 11 in textile mills, and 6 in other settings. Among the other investigations, two focused on building decontamination, one was a response to bioterrorism threats, and five involved other causes. Knowledge gained in these investigations helped guide the public health response to the October 2001 intentional release of B. anthracis, especially by addressing the management of anthrax threats, prevention of occupational anthrax, use of antibiotic prophylaxis in exposed persons, use of vaccination, spread of B. anthracis spores in aerosols, clinical diagnostic and laboratory confirmation methods, techniques for environmental sampling of exposed surfaces, and methods for decontaminating buildings. PMID:12396934

Immunization studies with attenuated strains of Bacillus anthracis.

PubMed Central

Ivins, B E; Ezzell, J W; Jemski, J; Hedlund, K W; Ristroph, J D; Leppla, S H

1986-01-01

Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with anthrax toxin in Fischer 344 rats and against aerosol or intramuscular challenge with virulent anthrax spores in Hartley guinea pigs. Animals immunized with toxigenic, nonencapsulated (pXO1+, pXO2-) strains survived toxin and spore challenge and demonstrated postimmunization antibody titers to the three components of anthrax toxin (protective antigen, lethal factor, and edema factor). Immunization with two nontoxigenic, encapsulated (pXO1-, pXO2+), Pasteur vaccine strains neither provided protection nor elicited titers to any of the toxin components. Therefore, to immunize successfully against anthrax toxin or spore challenge, attenuated, live strains of B. anthracis must produce the toxin components specified by the pXO1 plasmid. PMID:3084383

Anthrax vaccine-induced antibodies provide cross-species prediction of survival to aerosol challenge.

PubMed

Fay, Michael P; Follmann, Dean A; Lynn, Freyja; Schiffer, Jarad M; Stark, Gregory V; Kohberger, Robert; Quinn, Conrad P; Nuzum, Edwin O

2012-09-12

Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration's "Animal Rule," a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. U.S. government-sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. We examined data from 21 of those studies to determine whether an immunological bridge based on lethal toxin neutralization activity assay (TNA) can predict survival against an inhalation anthrax challenge within and across species and genera. The 21 studies were classified into 11 different settings, each of which had the same animal species, vaccine type and formulation, vaccination schedule, time of TNA measurement, and challenge time. Logistic regression models determined the contribution of vaccine dilution dose and TNA on prediction of survival. For most settings, logistic models using only TNA explained more than 75% of the survival effect of the models with dose additionally included. Cross-species survival predictions using TNA were compared to the actual survival and shown to have good agreement (Cohen's κ ranged from 0.55 to 0.78). In one study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques (actual survival, 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These data add support for the use of TNA as an immunological bridge between species to extrapolate data in animals to predict anthrax vaccine effectiveness in humans.

Evaluation of immunogenicity and efficacy of anthrax vaccine adsorbed for postexposure prophylaxis.

PubMed

Ionin, Boris; Hopkins, Robert J; Pleune, Brett; Sivko, Gloria S; Reid, Frances M; Clement, Kristin H; Rudge, Thomas L; Stark, Gregory V; Innes, Alison; Sari, Suha; Guina, Tina; Howard, Cris; Smith, Jeffrey; Swoboda, M Lisa; Vert-Wong, Ekaterina; Johnson, Virginia; Nabors, Gary S; Skiadopoulos, Mario H

2013-07-01

Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone.

Anthrax. William Smith Greenfield, M.D., F.R.C.P., Professor Superintendent, the Brown Animal Sanatory Institution (1878-81). Concerning the priority due to him for the production of the first vaccine against anthrax.

PubMed Central

Tigertt, W. D.

1980-01-01

The purpose of this paper is to draw attention to the fact that W. S. Greenfield, working at the Brown Animal Sanatory Institution in London, prepared an effective vaccine against anthrax and described his results some months before the experiment of Pasteur at Pouilly-le-fort. Partly through lack of financial support and partly due to opposition by the antivivisectionists, Greenfield was forced to confine his experiments to a small number of animals, but his results were nevertheless conclusive. He showed that by continuous subculture in a fluid medium that the anthrax bacillus progressively lost its virulence, until it was harmless even to the most susceptible animal, the mouse. The injection of suitably attenuated organisms into cattle rendered them immune to the subsequent injection of virulent anthrax bacilli. Greenfield's work has been overlooked or neglected, and he has never received the credit due him. It is only fitting that his work should be acknowledged in the centenary of the year in which it was described. The following account is composed primarily of quotations from his published papers. For additional information on Greenfield, reference may be made to the series of papers by Wilson (1979 a, b). It may be pointed out that the method of attenuating the virulence of bacilli recorded by Pasteur in relation to the bacillus of fowl cholera was, like that of anthrax vaccine, anticipated by Greenfield. PMID:7007487

The Genome of a Bacillus Isolate Causing Anthrax in Chimpanzees Combines Chromosomal Properties of B. cereus with B. anthracis Virulence Plasmids

PubMed Central

Nattermann, Herbert; Brüggemann, Holger; Dupke, Susann; Wollherr, Antje; Franz, Tatjana; Pauli, Georg; Appel, Bernd; Liebl, Wolfgang; Couacy-Hymann, Emmanuel; Boesch, Christophe; Meyer, Frauke-Dorothee; Leendertz, Fabian H.; Ellerbrok, Heinz; Gottschalk, Gerhard; Grunow, Roland; Liesegang, Heiko

2010-01-01

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”. PMID:20634886

Pandemic Flu and Medical Biodefense Countermeasure Liability Limitation

DTIC Science & Technology

2010-02-12

covering countermeasures against other strains of influenza (including H1N1), anthrax, botulism , small pox, and acute radiation syndrome...Secretary of HHS has issued additional declarations covering various countermeasures against anthrax, botulism , acute radiation syndrome, smallpox, and

Strategies for the prevention of a successful biological warfare aerosol attack.

PubMed

Wiener, S L

1996-05-01

Biological warfare (BW) aerosol attacks are different from chemical attacks in that they may provide no warning/all clear signals that allow the soldier to put on or remove his M17/M40 protective mask. Methods are now being perfected to detect a BW aerosol cloud using an airborne (helicopter) pulsed laser system to scan the lower altitudes upwind from a troop concentration of corps size, and to sample and analyze the nature of the aerosol within a brief time interval. This system has certain limitations and vulnerabilities, since it is designed specifically to detect a line-type aerosol attack. Provision of, training with, and field use of a lightweight dust mist or HEPA filter respirator for each soldier is proposed for protection against undetected aerosol attacks. This particulate filter respirator would be issued in addition to the M17/M40 mask. Such a BW respirator will be able to purify the soldier's air by removing particles in the 0.3- to 15-micro m-diameter range with an efficiency of 98 to 100%. Particle size of BW aerosols is in the same range, with an optimum size for high-efficiency casualty production of 1 to 5 micro m mass median diameter. The proposed BW respirator will be lightweight; will require low inhalation pressures; will be comfortable to wear for prolonged periods; will not interfere with vision, hearing, and communication; and will not degrade overall effectiveness and performance to the degree observed with the M17/M40 masks. Such respirators would be worn as part of a contingency defense against an enemy likely to use BW agents. This respirator could be worn for prolonged periods when under threat of an undetectable BW attack during weather conditions favorable to the success of such an attack (i.e., low wind velocity and temperature inversion in the target area). In addition, tactically important assets such as command and control centers and missile batteries can also be protected continuously by air filtration systems powered by electricity (modular collective protection equipment). Vaccinations against anthrax, botulism, Q fever, plague, and tularemia are now available and immune protection against ricin and staphylococcal toxins appears feasible in the near future. Chemotherapy can also be provided for prophylaxis of infectious agents released on the battlefield. The vaccines and antibiotics can provide back-up protection against an unexpected BW attack during a period when the BW respirator is not in use or malfunctions due to a poor seal or filter leak. Enemy sites of biological weapon production, assembly, testing, and storage, and delivery vehicles can be targeted for destruction by bombs and/or missiles. An integrated, well-planned, BW defense with multiple components can decrease the likelihood of a successful enemy BW aerosol attack.

Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents

PubMed Central

Ramasamy, S; Liu, CQ; Tran, H; Gubala, A; Gauci, P; McAllister, J; Vo, T

2010-01-01

The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin – a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. PMID:20860656

Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents.

PubMed

Ramasamy, S; Liu, C Q; Tran, H; Gubala, A; Gauci, P; McAllister, J; Vo, T

2010-10-01

The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin - a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. © 2010 The Commonwealth of Australia. British Journal of Pharmacology © 2010 The British Pharmacological Society.

[Current status of anthrax or black fever].

PubMed

Chantal, J

1997-01-01

Although anthrax is one of the oldest recognized infectious diseases in the world, it remains widespread particularly in tropical zones such as Africa. The impact of this major zoonoses is further enhanced by the fact that the pulmonary form can be used for biological warfare. Recently there has been a revival of interest in anthrax and research has benefited greatly from advances in molecular biology. The main factors accounting for the virulence of Bacillus anthracis have been elucidated. The author reports current data concerning pathogenesis, epidemiology and diagnosis and reviews progress made in the field of prophylaxis especially with regard to vaccines.

Micromotors to capture and destroy anthrax simulant spores.

PubMed

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.

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime boost immunization strategy

PubMed Central

Baillie, Leslie W.J.; Rodriguez, Ana L.; Moore, Stephen; Atkins, Helen S.; Feng, Chiguang; Nataro, James P.; Pasetti, Marcela F.

2008-01-01

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [1]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax. PMID:18805452

Increased long-term immunity to Bacillus anthracis protective antigen in mice immunized with a CIA06B-adjuvanted anthrax vaccine.

PubMed

Wui, Seo Ri; Han, Ji Eun; Kim, Yeon Hee; Rhie, Gi-eun; Lee, Na Gyong

2013-04-01

Anthrax is an acute infectious disease caused by Bacillus anthracis. We previously reported that the adjuvant CIA06B, which consists of TLR4 agonist CIA05 and aluminum hydroxide (alum), enhanced the immune response to anthrax protective antigen (PA) in mice. This study was carried out to determine whether CIA06B can enhance long-term immune responses to PA in mice. BALB/c mice were immunized intramuscularly three times at 2-week intervals with recombinant PA alone or PA combined with alum or CIA06B. At 8 and 24 weeks post-immunization, the immunological responses including serum anti-PA IgG antibody titer, toxin-neutralizing antibody titer, splenic cytokine secretion and the frequency of PA-specific memory B cells were assessed. Compared with mice injected with PA alone or PA plus alum, mice injected with PA plus CIA06B had higher titers of serum anti-PA IgG antibodies, and higher frequencies of PA-specific memory B cells and interferon-γ secreting cells. Furthermore, anti-PA antibodies induced by CIA06B were more effective in neutralizing anthrax toxin. These results demonstrated that CIA06B is capable of providing long-term immunity when used as an adjuvant in a PA-based anthrax vaccine.

Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys.

PubMed

Chabot, Donald J; Joyce, Joseph; Caulfield, Michael; Cook, James; Hepler, Robert; Wang, Su; Vietri, Nicholas J; Ruthel, Gordon; Shoop, Wesley; Pitt, Louise; Leffel, Elizabeth; Ribot, Wilson; Friedlander, Arthur M

2012-01-20

Bacillus anthracis, the causative agent of anthrax, is recognized as one of the most serious bioterrorism threats. The current human vaccines are based on the protective antigen component of the anthrax toxins. Concern about possible vaccine resistant strains and reliance on a single antigen has prompted the search for additional immunogens. Bacterial capsules, as surface-expressed virulence factors, are well-established components of several licensed vaccines. In a previous study we showed that an anthrax vaccine consisting of the B. anthracis poly-γ-D-glutamic acid capsule covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B protected mice against parenteral B. anthracis challenge. Here we tested this vaccine in rabbits and monkeys against an aerosol spore challenge. The vaccine induced anti-capsule antibody responses in both species, measured by ELISA and a macrophage opsono-adherence assay. While rabbits were not protected against a high aerosol challenge dose, significant protection was observed in monkeys receiving the capsule conjugate vaccine. The results confirm that the capsule is a protective immunogen against anthrax, being the first non-toxin antigen shown to be efficacious in monkeys and suggest that addition of capsule may broaden and enhance the protection afforded by protective antigen-based vaccines. Published by Elsevier Ltd.

Inhalation Anthrax: Dose Response and Risk Analysis

PubMed Central

Thran, Brandolyn; Morse, Stephen S.; Hugh-Jones, Martin; Massulik, Stacey

2008-01-01

The notion that inhalation of a single Bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. Risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. The difficulty in achieving transparency for biothreat risk is magnified by misinformation and poor characterization of both dose-response relationships and the driving mechanisms that cause susceptibility or resistance to disease progression. Regrettably, this entrenchment unnecessarily restricts preparedness planning to a single response scenario: decontaminate until no spores are detectable in air, water, or on surfaces—essentially forcing a zero-tolerance policy inconsistent with the biology of anthrax. We present evidence about inhalation anthrax dose-response relationships, including reports from multiple studies documenting exposures insufficient to cause inhalation anthrax in laboratory animals and humans. The emphasis of the article is clarification about what is known from objective scientific evidence for doses of anthrax spores associated with survival and mortality. From this knowledge base, we discuss the need for future applications of more formal risk analysis processes to guide development of alternative non-zero criteria or standards based on science to inform preparedness planning and other risk management activities. PMID:18582166

Investigation, control and epizootiology of anthrax in a geographically isolated, free-roaming bison population in northern Canada.

PubMed Central

Gates, C C; Elkin, B T; Dragon, D C

1995-01-01

In July 1993 anthrax caused significant mortality in an isolated, free-ranging population of bison (Bos bison athabascae) west of Great Slave Lake in the Northwest Territories. There was no previous record of anthrax in this area. An emergency response was undertaken to reduce the scale of environmental contamination and dissemination of anthrax spores and hence to reduce the likelihood of future outbreaks. One-hundred-and-seventy-two bison, 3 moose (Alces alces), and 3 black bear (Ursus americanus) carcasses were found. Visual detection of carcasses was enhanced with the use of an airborne, remote infrared sensing camera mounted externally on a helicopter. Fifty-five percent of the carcasses were located in forested or shrub-covered sites where detection would not have been likely without the thermal imaging equipment. Carcasses were disposed of by incineration and the sites were decontaminated with formaldehyde. Application of formaldehyde to carcasses prevented scavenging. The outbreak occurred after a prolonged period of drying between April and mid-July 1993 which followed several successive years of flooding of bison habitat. The "spore concentration hypothesis" provides the most conservative explanation for the occurrence of anthrax under the observed conditions. Images Fig. 1. Fig. 2. PMID:8548686

Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia.

PubMed

Pérez-Tanoira, Ramón; Ramos, Jose Manuel; Prieto-Pérez, Laura; Tesfamariam, Abraham; Balcha, Seble; Tissiano, Gabre; Cabello, Alfonso; Cuadros, Juan; Rodríguez-Valero, Natalia; Barreiro, Pablo; Reyes, Francisco; Górgolas, Miguel

2017-12-23

Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 - 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

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

PubMed

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

2015-02-01

DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax. Copyright © 2015 Elsevier B.V. All rights reserved.

Jane Austen and Addison's disease: an unconvincing diagnosis.

PubMed

White, K G

2009-12-01

Jane Austen's letters describe a two-year deterioration into bed-ridden exhaustion, with unusual colouring, bilious attacks and rheumatic pains. In 1964, Zachary Cope postulated tubercular Addison's to explain her symptoms and her relatively pain-free illness. Literary scholars later countered this posthumous diagnosis on grounds that are not well substantiated, while medical authors supported his conclusion. Important symptoms reported by contemporary Addison's patients-mental confusion, generalised pain and suffering, weight loss and anorexia-are absent from Jane Austen's letters. Thus, by listening to the patient's perspective, we can conclude it is unlikely that Addison's disease caused Jane Austen's demise. Disseminated bovine tuberculosis would offer a coherent explanation for her symptoms, so that Cope's original suggestion of infective tuberculosis as the cause of her illness may have been correct.

A generic open-source software framework supporting scenario simulations in bioterrorist crises.

PubMed

Falenski, Alexander; Filter, Matthias; Thöns, Christian; Weiser, Armin A; Wigger, Jan-Frederik; Davis, Matthew; Douglas, Judith V; Edlund, Stefan; Hu, Kun; Kaufman, James H; Appel, Bernd; Käsbohrer, Annemarie

2013-09-01

Since the 2001 anthrax attack in the United States, awareness of threats originating from bioterrorism has grown. This led internationally to increased research efforts to improve knowledge of and approaches to protecting human and animal populations against the threat from such attacks. A collaborative effort in this context is the extension of the open-source Spatiotemporal Epidemiological Modeler (STEM) simulation and modeling software for agro- or bioterrorist crisis scenarios. STEM, originally designed to enable community-driven public health disease models and simulations, was extended with new features that enable integration of proprietary data as well as visualization of agent spread along supply and production chains. STEM now provides a fully developed open-source software infrastructure supporting critical modeling tasks such as ad hoc model generation, parameter estimation, simulation of scenario evolution, estimation of effects of mitigation or management measures, and documentation. This open-source software resource can be used free of charge. Additionally, STEM provides critical features like built-in worldwide data on administrative boundaries, transportation networks, or environmental conditions (eg, rainfall, temperature, elevation, vegetation). Users can easily combine their own confidential data with built-in public data to create customized models of desired resolution. STEM also supports collaborative and joint efforts in crisis situations by extended import and export functionalities. In this article we demonstrate specifically those new software features implemented to accomplish STEM application in agro- or bioterrorist crisis scenarios.

Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax.

PubMed

Wycoff, Keith L; Belle, Archana; Deppe, Dorothée; Schaefer, Leah; Maclean, James M; Haase, Simone; Trilling, Anke K; Liu, Shihui; Leppla, Stephen H; Geren, Isin N; Pawlik, Jennifer; Peterson, Johnny W

2011-01-01

Inhalational anthrax, a zoonotic disease caused by the inhalation of Bacillus anthracis spores, has a ∼50% fatality rate even when treated with antibiotics. Pathogenesis is dependent on the activity of two toxic noncovalent complexes: edema toxin (EdTx) and lethal toxin (LeTx). Protective antigen (PA), an essential component of both complexes, binds with high affinity to the major receptor mediating the lethality of anthrax toxin in vivo, capillary morphogenesis protein 2 (CMG2). Certain antibodies against PA have been shown to protect against anthrax in vivo. As an alternative to anti-PA antibodies, we produced a fusion of the extracellular domain of human CMG2 and human IgG Fc, using both transient and stable tobacco plant expression systems. Optimized expression led to the CMG2-Fc fusion protein being produced at high levels: 730 mg/kg fresh leaf weight in Nicotiana benthamiana and 65 mg/kg in N. tabacum. CMG2-Fc, purified from tobacco plants, fully protected rabbits against a lethal challenge with B. anthracis spores at a dose of 2 mg/kg body weight administered at the time of challenge. Treatment with CMG2-Fc did not interfere with the development of the animals' own immunity to anthrax, as treated animals that survived an initial challenge also survived a rechallenge 30 days later. The glycosylation of the Fc (or lack thereof) had no significant effect on the protective potency of CMG2-Fc in rabbits or on its serum half-life, which was about 5 days. Significantly, CMG2-Fc effectively neutralized, in vitro, LeTx-containing mutant forms of PA that were not neutralized by anti-PA monoclonal antibodies.

Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate.

PubMed

Savransky, Vladimir; Shearer, Jeffry D; Gainey, Melicia R; Sanford, Daniel C; Sivko, Gloria S; Stark, Gregory V; Li, Na; Ionin, Boris; Lacy, Michael J; Skiadopoulos, Mario H

2017-09-05

The anthrax vaccine candidate AV7909 is being developed as a next generation vaccine for a post-exposure prophylaxis (PEP) indication against anthrax. AV7909 consists of the Anthrax Vaccine Adsorbed (AVA, BioThrax®) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (ODN) compound, CPG 7909. The addition of CPG 7909 to AVA enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making AV7909 a suitable next-generation vaccine for use in a PEP setting. The studies described here provide initial information on AV7909-induced toxin-neutralizing antibody (TNA) levels associated with the protection of animals from lethal Bacillus anthracis challenge. Guinea pigs or nonhuman primates (NHPs) were immunized on Days 0 and 28 with various dilutions of AV7909, AVA or a saline or Alhydrogel+CPG 7909 control. Animals were challenged via the inhalational route with a lethal dose of aerosolized B. anthracis (Ames strain) spores and observed for clinical signs of disease and mortality. The relationship between pre-challenge serum TNA levels and survival following challenge was determined in order to calculate a threshold TNA level associated with protection. Immunisation with AV7909 induced a rapid, highly protective TNA response in guinea pigs and NHPs. Surprisingly, the TNA threshold associated with a 70% probability of survival for AV7909 immunized animals was substantially lower than the threshold which has been established for the licensed AVA vaccine. The results of this study suggest that the TNA threshold of protection against anthrax could be modified by the addition of an immune stimulant such as CPG 7909 and that the TNA levels associated with protection may be vaccine-specific. Copyright © 2017. Published by Elsevier Ltd.

Composite Sampling Approaches for Bacillus anthracis Surrogate Extracted from Soil

PubMed Central

France, Brian; Bell, William; Chang, Emily; Scholten, Trudy

2015-01-01

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. PMID:26714315

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

PubMed

Ghosh, N; Gunti, D; Lukka, H; Reddy, B R; Padmaja, Jyothi; Goel, A K

2015-08-01

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

Anthrax

MedlinePlus

... spores during processes such as tanning hides and processing wool. Breathing in spores means a person has been exposed to anthrax. But it does not mean the person will have symptoms. The bacterial spores must germinate or sprout (the same way a seed sprouts before a plant grows) before the actual ...

Serologic Surveillance of Anthrax in the Serengeti Ecosystem, Tanzania, 1996–2009

PubMed Central

Lembo, Tiziana; Auty, Harriet; Beesley, Cari A.; Bessell, Paul; Packer, Craig; Halliday, Jo; Fyumagwa, Robert; Hoare, Richard; Ernest, Eblate; Mentzel, Christine; Mlengeya, Titus; Stamey, Karen; Wilkins, Patricia P.; Cleaveland, Sarah

2011-01-01

Bacillus anthracis, the bacterium that causes anthrax, is responsible for varying death rates among animal species. Difficulties in case detection, hazardous or inaccessible carcasses, and misdiagnosis hinder surveillance. Using case reports and a new serologic assay that enables multispecies comparisons, we examined exposure to and illness caused by B. anthracis in different species in the Serengeti ecosystem in Tanzania during 1996–2009 and the utility of serosurveillance. High seroprevalence among carnivores suggested regular nonfatal exposure. Seropositive wildebeest and buffalo showed that infection was not invariably fatal among herbivores, whereas absence of seropositivity in zebras and frequent detection of fatal cases indicated high susceptibility. Exposure patterns in dogs reflected known patterns of endemicity and provided new information about anthrax in the ecosystem, which indicated the potential of dogs as indicator species. Serosurveillance is a valuable tool for monitoring and detecting anthrax and may shed light on mechanisms responsible for species-specific variability in exposure, susceptibility, and mortality rates. PMID:21392428

Cell-wall preparation containing poly-γ-D-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.

PubMed

Candela, Thomas; Dumetz, Fabien; Tosi-Couture, Evelyne; Mock, Michèle; Goossens, Pierre L; Fouet, Agnès

2012-12-17

Bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. Many vaccine strategies were described to counteract anthrax infection. In contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. However, in animal models this vaccine is less efficient than the live vaccine. In this study, we analyzed the protection afforded by a single extractable surface element. The poly-γ-D-glutamate capsule is covalently linked to the peptidoglycan. A preparation of peptidoglycan-linked poly-γ-D-glutamate (GluPG) was tested for its immunogenicity and its protective effect. GluPG injection, in mice, elicited the production of specific antibodies directed against poly-glutamate and partially protected the animals against lethal challenges with a non-toxinogenic strain. When combined to protective antigen, GluPG immunization conferred full protection against cutaneous anthrax induced with a fully virulent strain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anthrax: Where Margins are Merging between Emerging Threats and Bioterrorism

PubMed Central

Banerjee, Dibyendu; Chakraborty, Baishali; Chakraborty, Banya

2017-01-01

National Institute of Allergy and Infectious Diseases has classified all the emerging infectious diseases agents under three categories. Among Category A priority pathogens comes Bacillus anthracis –the causative agent of Anthrax. It is a gram positive spore bearing bacteria, and the disease is typically associated with grazing animals, and affects the people as a zoonosis. The disease can be classically transmitted by three routes namely: cutaneous, gastrointestinal and pulmonary, with a fourth route recently identified as “injection anthrax”, seen in intravenous drug abusers. Cutaneous anthrax is the commonest form in humans, accounting for 95% of all the cases. There are two main virulence factors of this bacteria, a capsule and an exotoxin, each carried by a separate toxin. Two models have been used for explaining the pathogenesis of this infection. The earlier one or “Trojan horse” model is now replaced with “jail-break” model. Centers for disease control (CDC) has issued updated guidelines for diagnosis, post-exposure prophylaxis and treatment. For immunization, anthrax vaccine absorbed is available. PMID:28979006

Recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.

PubMed

Schiffer, Jarad M; McNeil, Michael M; Quinn, Conrad P

2016-09-01

Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.

Reanalysis of the anthrax epidemic in Rhodesia, 1978-1984.

PubMed

Wilson, James M; Brediger, Walter; Albright, Thomas P; Smith-Gagen, Julie

2016-01-01

In the mid-1980s, the largest epidemic of anthrax of the last 200 years was documented in a little known series of studies by Davies in The Central African Journal of Medicine . This epidemic involved thousands of cattle and 10,738 human cases with 200 fatalities in Rhodesia during the Counterinsurgency. Grossly unusual epidemiological features were noted that, to this day, have not been definitively explained. This study performed a historical reanalysis of the data to reveal an estimated geographic involvement of 245,750 km 2 , with 171,990 cattle and 17,199 human cases. Here we present the first documented geotemporal visualization of the human anthrax epidemic.

Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death

PubMed Central

Zhu, Ping Jun; Hobson, Peyton; Southall, Noel; Qiu, Cunping; Thomas, Craig J.; Lu, Jiamo; Inglese, James; Zheng, Wei; Leppla, Stephen H.; Bugge, Thomas H.; Austin, Christopher P.; Liu, Shihui

2009-01-01

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization. PMID:19540764

Anthrax and the Geochemistry of Soils in the Contiguous ...

EPA Pesticide Factsheets

Journal Article Soil geochemical data from sample sites located in counties that reported cases or outbreaks of anthrax since 2000 were evaluated against counties within the same states (MN, MT, ND, NV, OR, SD and TX) that did not report cases or outbreaks. These data identified the elements Ca, Mn, P and Sr as having statistically significant differences in concentrations between county type (anthrax occurrence versus no occurrence) within the total data set or in a majority of the states. Preliminary elemental threshold values present prospective investigative tools that can be refined through future high-resolution studies and present a path forward for understanding the geochemical constraints of other pathogens.

Compositions, devices and methods for SERS and LSPR

DOEpatents

Van Duyne, Richard P; Zhang, Xiaoyu; Zhao, Jing; Whitney, Alyson V; Elam, Jeffrey W; Schatz, George C; Stair, Peter C; Zou, Shengli; Young, Matthew; Lyandres, Olga

2014-01-14

The present invention relates to compositions, devices and methods for detecting microorganisms (e.g., anthrax). In particular, the present invention provides portable, surface-enhanced Raman biosensors, and associated substrates, and methods of using the same, for use in rapidly detecting and identifying microorganisms (e.g., anthrax).

CTC Sentinel. Volume 9, Issue 10, October 2016

DTIC Science & Technology

2016-10-01

attacking bridges with car bombs in order to obstruct security force reinforcement of the area; use of platoon-sized assaults to overrun police...complexes, bomb -making factories, supply points, and training camps.j In Au- gust 2015 insurgents extended their presence into the DRV groves south of...intent in his February 2004 letter to Ayman al-Zawahiri.33 The Islamic State has already begun to bait Badr and the PMF with local car bombings

Dragon’s Claws: The Improvised Explosive Device (IED) as a Weapon of Strategic Influence

DTIC Science & Technology

2009-03-01

admiration, respect, regret, sadness, guilt, and even anguish. They emotionally prepared themselves for loading their friends’ flag- draped coffins...including attacks on armoured vehicles, outposts and helicopters.164 AQI certainly has not limited its operations to the guidelines of Zarqawi’s letter...reports of American casualties, glimpses of flag- draped coffins, and stories of towns rallying behind the families of their fallen heroes accumulate in

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

PubMed Central

Balderas, Miriam A.; Nguyen, Chinh T. Q.; Terwilliger, Austen; Keitel, Wendy A.; Iniguez, Angelina; Torres, Rodrigo; Palacios, Frederico; Goulding, Celia W.

2016-01-01

Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine. PMID:27647868

Role of Visible Light-Activated Photocatalyst on the Reduction of Anthrax Spore-Induced Mortality in Mice

PubMed Central

Huang, Hsin-Hsien; Wong, Ming-Show; Lin, Hung-Chi; Chang, Hsin-Hou

2009-01-01

Background Photocatalysis of titanium dioxide (TiO2) substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO2 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. PMID:19132100

Biotechnology

NASA Image and Video Library

2003-01-22

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

The poison center role in biological and chemical terrorism.

PubMed

Krenzelok, E P; Allswede, M P; Mrvos, R

2000-10-01

Nuclear, biological and chemical (NBC) terrorism countermeasures are a major priority with municipalities, healthcare providers, and the federal government. Significant resources are being invested to enhance civilian domestic preparedness by conducting education at every response level in anticipation of a NBC terroristic incident. The key to a successful response, in addition to education, is integration of efforts as well as thorough communication and understanding the role that each agency would play in an actual or impending NBC incident. In anticipation of a NBC event, a regional counter-terrorism task force was established to identify resources, establish responsibilities and coordinate the response to NBC terrorism. Members of the task force included first responders, hazmat, law enforcement (local, regional, national), government officials, the health department, and the regional poison information center. Response protocols were developed and education was conducted, culminating in all members of the response task force becoming certified NBC instructors. The poison center participated actively in 3 incidents of suspected biologic and chemical terrorism: an alleged anthrax-contaminated letter sent to a women's health clinic; a possible sarin gas release in a high school: and a potential anthrax/ebola contamination incident at an international airport. All incidents were determined hoaxes. The regional response plan establishes the poison information center as a common repository for all cases in a biological or chemical incident. The poison center is one of several critical components of a regional counterterrorism response force. It can conduct active and passive toxicosurveillance and identify sentinel events. To be responsive, the poison center staff must be knowledgeable about biological and chemical agents. The development of basic protocols and a standardized staff education program is essential. The use of the RaPiD-T (R-recognition, P-protection, D-detection, T-triage/treatment) course can provide basic staff education for responding to this important but rare consultation to the poison center.

Pandemic Influenza Planning, United States, 1978–2008

PubMed Central

Strikas, Raymond A.; Gensheimer, Kathleen F.; Cox, Nancy J.; Redd, Stephen C.

2013-01-01

During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community’s response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises. PMID:23731839

Wide area restoration following biological contamination

NASA Astrophysics Data System (ADS)

Yang, Lynn; Hibbard, Wilthea; Edwards, Donna; Franco, David; Fruetel, Julie; Tucker, Mark; Einfeld, Wayne; Knowlton, Robert; Brown, Gary; Brockmann, John; Greenwalt, Robert; Miles, Robin; Raber, Ellen; Carlsen, Tina; Krauter, Paula; Dillon, Michael; MacQueen, Don; Intrepido, Tony; Hoppes, Bill; Wilson, Wendy; Mancieri, Sav

2008-04-01

Current understanding of how to restore a wide area that has been contaminated following a large biological attack is limited. The Department of Homeland Security and Department of Defense are executing a four-year collaborative program named the Interagency Biological Restoration Demonstration (IBRD) program. This program is aimed at developing technologies, methods, plans and policies necessary to restore a wide area, including military installations and critical infrastructures, in the event of a large outdoor aerosol release of anthrax. The IBRD program partner pilot city is the Seattle Urban Area to include Fort Lewis, WA and McChord Air Force Base. A front-end systems analysis was conducted as part of IBRD, to: 1) assess existing technologies and processes for wide area restoration; from this, 2) develop an "as-is" decision framework for wide area restoration; and 3) identify and prioritize capability gaps. Qualitative assessments and quantitative analyses, including sensitivity, timeline and case study analyses, were conducted to evaluate existing processes and rank capability gaps. This paper describes the approach and results from this front-end systems analysis.

Field application of the Numobag as a portable disposable isolation unit and for treating chemical, radiological or biologically induced wounds.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Keith A.; Felton, Robert; Vaughan, Courtenay Thomas

2005-04-01

Numotech Inc. has developed the Numobag{trademark}, a disposable, lightweight, wound healing device which produces Topical Hyperbaric Oxygen Therapy (THOT). The Numobag{trademark} is cost effective and has been clinically validated to heal large skin lesions rapidly and has proven to arrest wound advancement from several insidious forms of biological attack including dermal anthrax, small pox, necrotizing fasciitis etc. The Numobag{trademark} can treat mass casualties wounded by chemical/radiological burns or damaging biological exposures. The Numobag{trademark} can be a frontline tool as an isolation unit, reducing cross-contamination and infection of medical personnel. The heightened oxygen content kills organisms on the skin and inmore » the wound, avoids expensive hospital trash disposal procedures, and helps the flesh heal. The Numobag{trademark} requires high purity oxygen. Numotech Inc. is teaming with Sandia National Laboratories and Spektr Conversion in Russia to develop a cost effective, portable, low power oxygen generator.« less

APDS: Autonomous Pathogen Detection System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langlois, R G; Brown, S; Burris, L

An early warning system to counter bioterrorism, the Autonomous Pathogen Detection System (APDS) continuously monitors the environment for the presence of biological pathogens (e.g., anthrax) and once detected, it sounds an alarm much like a smoke detector warns of a fire. Long before September 11, 2001, this system was being developed to protect domestic venues and events including performing arts centers, mass transit systems, major sporting and entertainment events, and other high profile situations in which the public is at risk of becoming a target of bioterrorist attacks. Customizing off-the-shelf components and developing new components, a multidisciplinary team developed APDS,more » a stand-alone system for rapid, continuous monitoring of multiple airborne biological threat agents in the environment. The completely automated APDS samples the air, prepares fluid samples in-line, and performs two orthogonal tests: immunoassay and nucleic acid detection. When compared to competing technologies, APDS is unprecedented in terms of flexibility and system performance.« less

The importance of establishing a national health security preparedness index.

PubMed

Lumpkin, John R; Miller, Yoon K; Inglesby, Tom; Links, Jonathan M; Schwartz, Angela T; Slemp, Catherine C; Burhans, Robert L; Blumenstock, James; Khan, Ali S

2013-03-01

Natural disasters, infectious disease epidemics, terrorism, and major events like the nuclear incident at Fukushima all pose major potential challenges to public health and security. Events such as the anthrax letters of 2001, Hurricanes Katrina, Irene, and Sandy, severe acute respiratory syndrome (SARS) and West Nile virus outbreaks, and the 2009 H1N1 influenza pandemic have demonstrated that public health, emergency management, and national security efforts are interconnected. These and other events have increased the national resolve and the resources committed to improving the national health security infrastructure. However, as fiscal pressures force federal, state, and local governments to examine spending, there is a growing need to demonstrate both what the investment in public health preparedness has bought and where gaps remain in our nation's health security. To address these needs, the Association of State and Territorial Health Officials (ASTHO), through a cooperative agreement with the Centers for Disease Control and Prevention (CDC) Office of Public Health Preparedness and Response (PHPR), is creating an annual measure of health security and preparedness at the national and state levels: the National Health Security Preparedness Index (NHSPI).

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

PubMed

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

2014-02-01

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

Coordinated Response to Reports of Possible Anthrax Contamination, Idaho, 2001

PubMed Central

Hudson, Richard; Barnes, Shana; Hahn, Christine

2002-01-01

In 2001, the intentional release of anthrax spores in the eastern United States increased concern about exposure to anthrax nationwide, and residents of Idaho sought assistance. Response from state and local agencies was required, increasing the strain on epidemiologists, laboratorians, and communications personnel. In late 2001, Idaho’s public health communications system handled 133 calls about suspicious powders. For each call, a multiagency bridge call was established, and participants (public health officials, epidemiologists, police, Federal Bureau of Investigation personnel, hazardous materials officials, and others) determined which samples would be tested by the state public health laboratory. A triage system for calls helped relieve the burden on public safety and health systems. PMID:12396922

Reanalysis of the anthrax epidemic in Rhodesia, 1978–1984

PubMed Central

Brediger, Walter; Albright, Thomas P.; Smith-Gagen, Julie

2016-01-01

In the mid-1980s, the largest epidemic of anthrax of the last 200 years was documented in a little known series of studies by Davies in The Central African Journal of Medicine. This epidemic involved thousands of cattle and 10,738 human cases with 200 fatalities in Rhodesia during the Counterinsurgency. Grossly unusual epidemiological features were noted that, to this day, have not been definitively explained. This study performed a historical reanalysis of the data to reveal an estimated geographic involvement of 245,750 km2, with 171,990 cattle and 17,199 human cases. Here we present the first documented geotemporal visualization of the human anthrax epidemic. PMID:27867766

New Insights into Gastrointestinal Anthrax Infection

PubMed Central

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

2014-01-01

Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the “archetype zoonotic” pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target establishment of infection. PMID:25577136

Portable Anthrax Testing with Lab-in-a-Pocket

ScienceCinema

Finley, Melissa; Koskelo, Markku; Edwards, Thayne

2018-05-30

BaDx (Bacillus anthracis Diagnostics) is a lab-in-a-pocket device to sample, sense, and diagnose bacteria that cause anthrax. It accomplishes these tasks in environments with no power, refrigerated storage, or laboratory equipment. BaDx was designed to be used with minimal or no training, and to keep handlers safe.

World Epidemiology Review No. 99

DTIC Science & Technology

1978-08-02

by microbes Brucellosis, bacterial anthrax, symptomatic anthrax, aviary cholera, sheep pox, farcy in cattle, aphthous fever, bluetongue , heartwater...equine epizootic lymphangitis, Teschen’s disease, hemorrhagic septicemia, tuberculosis, rabies, equine and bovine plague, swine salmonellosis... bovine peripneumonia. 57 Some of these diseases, whose list is far from exhaustive, are infectious. Others are contagious, and finally, a certain number

Portable Anthrax Testing with Lab-in-a-Pocket

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finley, Melissa; Koskelo, Markku; Edwards, Thayne

2014-10-24

BaDx (Bacillus anthracis Diagnostics) is a lab-in-a-pocket device to sample, sense, and diagnose bacteria that cause anthrax. It accomplishes these tasks in environments with no power, refrigerated storage, or laboratory equipment. BaDx was designed to be used with minimal or no training, and to keep handlers safe.

Injectional anthrax at a Scottish district general hospital.

PubMed

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

2015-04-01

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

A Novel Immunogenic Spore Coat-Associated Protein in Bacillus Anthracis: Characterization via Proteomics Approaches and a Vector-Based Vaccine System

PubMed Central

Liu, Yu-Tsueng; Lin, Shwu-Bin; Huang, Cheng-Po; Huang, Chun-Ming

2007-01-01

New generation anthrax vaccines have been actively explored with the aim of enhancing efficacies and decreasing undesirable side effects that could be caused by licensed vaccines. Targeting novel antigens and/or eliminating the requirements for multiple needle injections and adjuvants are major objectives in the development of new anthrax vaccines. Using proteomics approaches, we identified a spore coat-associated protein (SCAP) in Bacillus anthracis. An E. coli vector-based vaccine system was used to determine the immunogenicity of SCAP. Mice generated detectable SCAP antibodies three weeks after intranasal immunization with an intact particle of ultraviolet (UV)-irradiated E. coli vector overproducing SCAP. The production of SCAP antibodies was detected via western blotting and SCAP-spotted antigen-arrays. The adjuvant effect of a UV-irradiated E. coli vector eliminates the necessity of boosting and the use of other immunomodulators which will foster the screening and manufacturing of new generation anthrax vaccines. More importantly, the immunogenic SCAP may potentially be a new candidate for the development of anthrax vaccines. PMID:18029197

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

PubMed

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

2016-01-01

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

A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax.

PubMed

Arévalo, Maria T; Li, Junwei; Diaz-Arévalo, Diana; Chen, Yanping; Navarro, Ashley; Wu, Lihong; Yan, Yongyong; Zeng, Mingtao

2017-03-01

Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of three tandem M2e repeats plus HA2, in combination with a detoxified anthrax oedema toxin delivery system (EFn plus PA) to enhance immune responses. The EFn-3×M2e-HA2 plus PA vaccine formulation elicited robust, antigen-specific, IgG responses; and was protective against heterologous influenza viral challenge when intranasally delivered to mice three times. Moreover, use of the detoxified anthrax toxin system as an adjuvant had the additional benefit of generating protective immunity against anthrax. Hence, this novel vaccine strategy could potentially address two major emerging public health and biodefence threats. © 2016 John Wiley & Sons Ltd.

A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge

PubMed Central

Klas, S.D.; Petrie, C.R.; Warwood, S.J.; Williams, M.S.; Olds, C.L.; Stenz, J.P.; Cheff, A.M.; Hinchcliffe, M.; Richardson, C.; Wimer, S.

2009-01-01

Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150 μg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150 μg rPA, 150 μg rPA + 150 μg of a conjugated 10-mer peptide representing the B. anthracis capsule (conj), or 150 μg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys®). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA + conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p = 0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA + conj immunized groups (p = 0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later. PMID:18703110

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

PubMed

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

2014-02-01

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

Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy.

PubMed

Baillie, Leslie W J; Rodriguez, Ana L; Moore, Stephen; Atkins, Helen S; Feng, Chiguang; Nataro, James P; Pasetti, Marcela F

2008-11-11

We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax.

A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.

PubMed

Klas, S D; Petrie, C R; Warwood, S J; Williams, M S; Olds, C L; Stenz, J P; Cheff, A M; Hinchcliffe, M; Richardson, C; Wimer, S

2008-10-09

Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150microg rPA, 150microg rPA+150microg of a conjugated 10-mer peptide representing the Bacillus anthracis capsule (conj), or 150microg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA+conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p=0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA+conj immunized groups (p=0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later.

Gastrointestinal anthrax after an animal-hide drumming event - New Hampshire and Massachusetts, 2009.

PubMed

2010-07-23

On December 24, 2009, a woman aged 24 years from New Hampshire was confirmed to have gastrointestinal anthrax on the basis of clinical findings and a Bacillus anthracis blood culture isolate. Her symptoms began on December 5. One day before symptom onset, she had participated in a drumming event at a community organization's building where animal-hide drums of multiple ages and origins were played. This report describes the case and subsequent investigation, which identified 84 persons potentially exposed to anthrax, including those persons at the drumming event and those who lived or worked at the event site. Review of New Hampshire disease surveillance data and clinical microbiology records for periods before and after the event identified no additional anthrax cases. Initial qualitative environmental testing of the event site yielded three positive samples (two from drum heads and one composite sample of three electrical outlets in the main drumming room). Wider, targeted, semi-quantitative environmental testing of the site and additional drums yielded six positive samples (two from one drum and four from environmental locations in the building). These results suggested that aerosolization of spores from drumheads had occurred. All isolates obtained from environmental and drum samples matched the patient's isolate by multiple-locus variable-number tandem repeat analysis using eight loci (MLVA-8). Public health agencies and persons with exposure to animal-hide drums should be aware of the potential, although remote, risk for anthrax exposure associated with these drums.

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

PubMed Central

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

2014-01-01

Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 108 infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD50) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax. PMID:24307239

New insights into the biological effects of anthrax toxins: linking cellular to organismal responses

PubMed Central

Guichard, Annabel; Nizet, Victor; Bier, Ethan

2013-01-01

The anthrax toxins lethal toxin (LT) and edema toxin (ET), are essential virulence factors produced by B. anthracis. These toxins act during two distinct phases of anthrax infection. During the first, prodromal phase, which is often asymptomatic, anthrax toxins act on cells of the immune system to help the pathogen establish infection. Then, during the rapidly progressing (or fulminant) stage of the disease bacteria disseminate via a hematological route to various target tissues and organs, which are typically highly vascularized. As bacteria proliferate in the bloodstream LT and ET begin to accumulate rapidly reaching a critical threshold level that will cause death even when the bacterial proliferation is curtailed by antibiotics. During this final phase of infection the toxins cause an increase in vascular permeability and a decrease in function of target organs including the heart, spleen, kidney, adrenal gland, and brain. In this review, we examine the various biological effects of anthrax toxins, focusing on the fulminant stage of the disease and on mechanisms by which the two toxins may collaborate to cause cardiovascular collapse. We discuss normal mechanisms involved in maintaining vascular integrity and based on recent studies indicating that LT and ET cooperatively inhibit membrane trafficking to cell-cell junctions we explore several potential mechanisms by which the toxins may achieve their lethal effects. We also summarize the effects of other potential virulence factors secreted by B. anthracis and consider the role of toxic factors in the evolutionarily recent emergence of this devastating disease. PMID:21930233

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

PubMed

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.

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.

PubMed

Weiss, Shay; Altboum, Zeev; Glinert, Itai; Schlomovitz, Josef; Sittner, Assa; Bar-David, Elad; Kobiler, David; Levy, Haim

2015-12-01

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated.

PubMed

Dumas, Eric K; Garman, Lori; Cuthbertson, Hannah; Charlton, Sue; Hallis, Bassam; Engler, Renata J M; Choudhari, Shyamal; Picking, William D; James, Judith A; Farris, A Darise

2017-06-08

A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective. In this report we compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients (n=78) matched 1:2 for number of vaccinations and time post-vaccination, and evaluated whether the LF response contributes to LT neutralization in human recipients of AVP. PA response rates (≥95%) and PA IgG concentrations were similar in both groups; however, AVP recipients exhibited higher LT neutralization ED 50 values (AVP: 1464.0±214.7, AVA: 544.9±83.2, p<0.0001) and had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees (1%). Multiple regression analysis revealed that LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group. Affinity purified LF antibodies from two independent AVP recipients neutralized LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT neutralization. This study documents the benefit of including an LF component to PA-based anthrax vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease.

PubMed

Balderas, Miriam A; Nguyen, Chinh T Q; Terwilliger, Austen; Keitel, Wendy A; Iniguez, Angelina; Torres, Rodrigo; Palacios, Frederico; Goulding, Celia W; Maresso, Anthony W

2016-12-01

Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

PubMed

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.

A Heterodimer of a VHH (Variable Domains of Camelid Heavy Chain-only) Antibody That Inhibits Anthrax Toxin Cell Binding Linked to a VHH Antibody That Blocks Oligomer Formation Is Highly Protective in an Anthrax Spore Challenge Model*

PubMed Central

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

2015-01-01

Anthrax disease is caused by a toxin consisting of protective antigen (PA), lethal factor, and edema factor. Antibodies against PA have been shown to be protective against the disease. Variable domains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. Two classes of neutralizing VHHs were identified recognizing distinct, non-overlapping epitopes. One class recognizes domain 4 of PA at a well characterized neutralizing site through which PA binds to its cellular receptor. A second neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits conversion of the PA oligomer from “pre-pore” to its SDS and heat-resistant “pore” conformation while not preventing cleavage of full-length 83-kDa PA (PA83) by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The antibody prevents endocytosis of the cell surface-generated PA63 subunit but not preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and protected mice from anthrax toxin challenge with much better efficacy than the separate component VHHs. The VNA protected virtually all mice when separately administered at a 1:1 ratio to toxin and protected mice against Bacillus anthracis spore infection. Thus, our studies show the potential of VNAs as anthrax therapeutics. Due to their simple and stable nature, VNAs should be amenable to genetic delivery or administration via respiratory routes. PMID:25564615

Quantitative anti-PA IgG ELISA; assessment and comparability with the anthrax toxin neutralization assay in goats.

PubMed

Ndumnego, Okechukwu C; Crafford, Jannie; Beyer, Wolfgang; van Heerden, Henriette

2013-12-27

Presently, few data exist on the level and duration of anti-protective antigen (PA) IgG in vaccinated livestock. Various adaptation of enzyme-linked immunosorbent assays (ELISAs) have been developed in studies to assess immune response following vaccination, albeit mostly in laboratory rodent models. The quantitative anti-anthrax IgG ELISA in this study describes a method of enumerating the concentration of anti-PA specific IgG present in sera of immunized goats, with the aid of an affinity-purified caprine polyclonal anti-anthrax PA-83 IgG standard. This was compared with the anthrax toxin neutralization assay (TNA) which measures a functional subset of toxin neutralizing anti-PA IgG. The measured concentrations obtained in the standard curve correlated with the known concentration at each dilution. Percentage recovery of the standard concentrations ranged from 89 to 98% (lower and upper asymptote respectively). Mean correlation coefficient (r2) of the standard curve was 0.998. Evaluation of the intra-assay coefficient of variation showed ranges of 0.23-16.90% and 0.40-12.46% for days 28 and 140 sera samples respectively, following vaccination. The mean inter-assay coefficient of variation for triplicate samples repeated on 5 different days was 18.53 and 12.17% for days 28 and 140 sera samples respectively. Spearman's rank correlation of log-transformed IgG concentrations and TNA titres showed strong positive correlation (rs = 0.942; p = 0.01). This study provides evidence that an indirect ELISA can be used for the quantification of anti-anthrax PA IgG in goats with the added advantage of using single dilutions to save time and resources. The use of such related immunoassays can serve as potential adjuncts to potency tests for Sterne and other vaccine types under development in ruminant species. This is the first report on the correlation of polyclonal anti-anthrax PA83 antibody with the TNA in goats.

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

PubMed Central

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%–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. PMID:24971906

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

PubMed

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

2016-01-06

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Alternative pre-approved and novel therapies for the treatment of anthrax.

PubMed

Head, Breanne M; Rubinstein, Ethan; Meyers, Adrienne F A

2016-11-03

Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies. A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009. The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered. Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.

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

PubMed

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

2015-03-06

Anthrax disease is caused by a toxin consisting of protective antigen (PA), lethal factor, and edema factor. Antibodies against PA have been shown to be protective against the disease. Variable domains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. Two classes of neutralizing VHHs were identified recognizing distinct, non-overlapping epitopes. One class recognizes domain 4 of PA at a well characterized neutralizing site through which PA binds to its cellular receptor. A second neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits conversion of the PA oligomer from "pre-pore" to its SDS and heat-resistant "pore" conformation while not preventing cleavage of full-length 83-kDa PA (PA83) by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The antibody prevents endocytosis of the cell surface-generated PA63 subunit but not preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and protected mice from anthrax toxin challenge with much better efficacy than the separate component VHHs. The VNA protected virtually all mice when separately administered at a 1:1 ratio to toxin and protected mice against Bacillus anthracis spore infection. Thus, our studies show the potential of VNAs as anthrax therapeutics. Due to their simple and stable nature, VNAs should be amenable to genetic delivery or administration via respiratory routes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Designing Inhibitors of Anthrax Toxin

PubMed Central

Nestorovich, Ekaterina M.; Bezrukov, Sergey M.

2014-01-01

Introduction Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates, and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded “for the development of multiscale models for complex chemical systems” once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial and error approach to a minimum. The “rational drug design” term is rather comprehensive as it includes all contemporary methods of drug discovery where serendipity and screening are substituted by the information-guided search for new and existing compounds. Successful implementation of these innovative drug discovery approaches is inevitably preceded by learning the physics, chemistry, and physiology of functioning of biological structures under normal and pathological conditions. Areas covered This article provides an overview of the recent rational drug design approaches to discover inhibitors of anthrax toxin. Some of the examples include small-molecule and peptide-based post-exposure therapeutic agents as well as several polyvalent compounds. The review also directs the reader to the vast literature on the recognized advances and future possibilities in the field. Expert opinion Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (PA-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, in our view, the situation is still insecure. The FDA’s animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Besides, unlike PA, which is known to be unstable, LF remains active in cells and in animal tissues for days. Therefore, the effectiveness of the post-exposure treatment of the individuals with anti-PA therapeutics can be time-dependent, requiring coordinated use of membrane permeable small-molecule inhibitors, which block the LF and EF enzymatic activity intracellularly. The desperate search for an ideal anthrax antitoxin allowed researchers to gain important knowledge of the basic principles of small-molecule interactions with their protein targets that could be easily transferred to other systems. At the same time, better identification and validation of anthrax toxin therapeutic targets at the molecular level, which include understanding of the physical forces underlying the target/drug interaction, as well as elucidation of the parameters determining the corresponding therapeutic windows, require further examination. PMID:24447197

Structure of the Anthrax Research Literature

DTIC Science & Technology

2006-01-01

4; identification 4; staphylococcus - aureus 3; pharmacology & pharmacy 3; microbiology 3; pharmacology & pharmacy 2; biotechnology & applied...proteins 4; microbiology 4; escherichia-coli 4; bacillus-anthracis 4; cell-wall 3; staphylococcus - aureus 3 Country usa 9; france 7; england 2...pathogen detection using a microchip PCR array Instrument 199 In vitro selection of DNA aptamers to anthrax spores with electrochemiluminescence

Investigation of an anthrax outbreak in Alberta in 1999 using a geographic information system

PubMed Central

Parkinson, Robert; Rajic, Andrijana; Jenson, Chris

2003-01-01

A Geographic Information System was used to document an anthrax outbreak in Alberta in 1999 and to describe the physical and environmental conditions of the area. The majority of infected farms were located on poorly drained organic soils. Regulatory agencies should consider adopting this tool for animal disease outbreak investigations. PMID:12715984

New insights into gastrointestinal anthrax infection.

PubMed

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

2015-03-01

Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Advances in the development of next-generation anthrax vaccines.

PubMed

Friedlander, Arthur M; Little, Stephen F

2009-11-05

Anthrax, a disease of herbivores, only rarely infects humans. However, the threat of using Bacillus anthracis, the causative agent, to intentionally produce disease has been the impetus for development of next-generation vaccines. Two licensed vaccines have been available for human use for several decades. These are composed of acellular culture supernatants containing the protective antigen (PA) component of the anthrax toxins. In this review we summarize the various approaches used to develop improved vaccines. These efforts have included the use of PA with newer adjuvants and delivery systems, including bacterial and viral vectors and DNA vaccines. Attempts to broaden the protection afforded by PA-based vaccines have focused on adding other B. anthracis components, including spore and capsule antigens.

Expression, Purification, Crystallization And Preliminary X-Ray Studies of a Prolyl-4-Hydroxylase Protein From Bacillus Anthracis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, M.A.; Scott, E.E.; Limburg, J.

2009-05-26

Collagen prolyl-4-hydroxylase (C-P4H) catalyzes the hydroxylation of specific proline residues in procollagen, which is an essential step in collagen biosynthesis. A new form of P4H from Bacillus anthracis (anthrax-P4H) that shares many characteristics with the type I C-P4H from human has recently been characterized. The structure of anthrax-P4H could provide important insight into the chemistry of C-P4Hs and into the function of this unique homodimeric P4H. X-ray diffraction data of selenomethionine-labeled anthrax-P4H recombinantly expressed in Escherichia coli have been collected to 1.4 {angstrom} resolution.

Pediatric Anthrax Clinical Management

PubMed Central

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

2015-01-01

Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as “children”) in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults. PMID:24777226

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

PubMed

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.

Summary and results of the joint WMD-DAC/Alameda County bioterrorism response plan exercise.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manley, Dawn Kataoka; Lipkin, Joel; West, Todd H.

2003-11-01

On June 12,2003, the Alameda County Public Health Department and Sandia National Laboratories/CA jointly conducted an exercise that used a Weapons of Mass Destruction-Decision Analysis Center (WMD-DAC) bioterrorism attack simulation to test the effectiveness of the county's emergency response plan. The exercise was driven by an assumed release (in the vicinity of the Berkeley Marina), and subsequent spread, of a small quantity of aerosolized, weapons-grade anthrax spores. The simulation used several key WMD-DAC capabilities, namely: (1) integration with an atmospheric dispersion model to calculate expected dose levels in the affected areas, (2) a individual-tracking capability for both infected and non-infectedmore » persons as they made decisions, sought treatment, and received prophylaxis drugs, and (3) a user interface that allows exercise participants to affect the scenario evolution and outcome. The analysis of the county's response plan included documenting and reviewing the decisions made by participants during the exercise. Twenty-six local and regional officials representing the health care system, emergency medical services and law enforcement were involved in responding to the simulated attack. The results of this joint effort include lessons learned both by the Alameda County officials regarding implementation of their bioterrorism response plan and by the Sandia representatives about conducting exercises of this type. These observations are reviewed in this report, and they form a basis for providing a better understanding of group/individual decision processes and for identifying effective communication options among decision makers.« less

Freeing France: The Allies, the Resistance, and the JEDBURGHs

DTIC Science & Technology

2008-01-01

attack. Grall suggested and SFHQ agreed the signal would be “Le Chapeau de Napoleon est-il toujours a Perros -Guirec?” (“Is Napoleon’s hat still at... Perros - Guirec?”). After an unsuccessful attempt on 4 July, GILES finally parachuted into the French night on 8/9 July from a Carpetbagger B-24.47...9 and Knox, letter. Napolean’s Hat is the name of a rock formation off the coast of France near the town of Perros -Guirec. 38 “FREDERICK, June Moon

Generation and Characterization of Human Monoclonal Antibodies Targeting Anthrax Protective Antigen following Vaccination with a Recombinant Protective Antigen Vaccine.

PubMed

Chi, Xiangyang; Li, Jianmin; Liu, Weicen; Wang, Xiaolin; Yin, Kexin; Liu, Ju; Zai, Xiaodong; Li, Liangliang; Song, Xiaohong; Zhang, Jun; Zhang, Xiaopeng; Yin, Ying; Fu, Ling; Xu, Junjie; Yu, Changming; Chen, Wei

2015-05-01

The anthrax protective antigen (PA) is the central component of the three-part anthrax toxin, and it is the primary immunogenic component in the approved AVA anthrax vaccine and the "next-generation" recombinant PA (rPA) anthrax vaccines. Animal models have indicated that PA-specific antibodies (AB) are sufficient to protect against infection with Bacillus anthracis. In this study, we investigated the PA domain specificity, affinity, mechanisms of neutralization, and synergistic effects of PA-specific antibodies from a single donor following vaccination with the rPA vaccine. Antibody-secreting cells were isolated 7 days after the donor received a boost vaccination, and 34 fully human monoclonal antibodies (hMAb) were identified. Clones 8H6, 4A3, and 22F1 were able to neutralize lethal toxin (LeTx) both in vitro and in vivo. Clone 8H6 neutralized LeTx by preventing furin cleavage of PA in a dose-dependent manner. Clone 4A3 enhanced degradation of nicked PA, thereby interfering with PA oligomerization. The mechanism of 22F1 is still unclear. A fourth clone, 2A6, that was protective only in vitro was found to be neutralizing in vivo in combination with a toxin-enhancing antibody, 8A7, which binds to domain 3 of PA and PA oligomers. These results provide novel insights into the antibody response elicited by the rPA vaccine and may be useful for PA-based vaccine and immunotherapeutic cocktail design. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity.

PubMed

Yamamoto, Brent J; Shadiack, Annette M; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N; O'Connor, Edward; Gonzales, Nestor; Mondick, John; French, Jonathan; Stark, Gregory V; Fisher, Alan C; Casey, Leslie S; Serbina, Natalya V

2016-10-01

Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with obiltoxaximab in both early and late stages of inhalational anthrax. Copyright © 2016 Yamamoto et al.

Anthrax

DTIC Science & Technology

1984-11-21

acute or subacute, with fever , dullness, anorexia, and inflammatory edema of the face, throat, and neck (1); however, some individuals may die...involvement, blood-stained froth may be discharged from the mouth. Petechial hemorrhages often occur on the skin. With alimentary involvement, there is...which are hot and painful. Other symptoms Include high fever , severe depression, anorexia, and dyspnea which occur over the course of 2 to 4 days. Anthrax

Anthrax (Lecture Aids) - USSR .

DTIC Science & Technology

1961-08-14

cutting up its carcass and intestines are disinfected or, if they are not valuable, are burned. In the quarters of infected persons, bed linen and...objects which could have come into contact with discharges by the patient are disinfected . Industrial anthrax infections. Infection occurs in...spores. As we have already mentioned, spores’occur on the surface of wool and hair. YThis facilitates, disinfection ; excellent results are

Anthrax in Western and Central African great apes.

PubMed

Leendertz, Fabian H; Lankester, Felix; Guislain, Patrick; Néel, Cécile; Drori, Ofir; Dupain, Jef; Speede, Sheri; Reed, Patricia; Wolfe, Nathan; Loul, Severin; Mpoudi-Ngole, E; Peeters, Martine; Boesch, Christophe; Pauli, Georg; Ellerbrok, Heinz; Leroy, Eric M

2006-09-01

During the period of December 2004 to January 2005, Bacillus anthracis killed three wild chimpanzees (Pan troglodytes troglodytes) and one gorilla (Gorilla gorilla gorilla) in a tropical forest in Cameroon. While this is the second anthrax outbreak in wild chimpanzees, this is the first case of anthrax in gorillas ever reported. The number of great apes in Central Africa is dramatically declining and the populations are seriously threatened by diseases, mainly Ebola. Nevertheless, a considerable number of deaths cannot be attributed to Ebola virus and remained unexplained. Our results show that diseases other than Ebola may also threaten wild great apes, and indicate that the role of anthrax in great ape mortality may have been underestimated. These results suggest that risk identification, assessment, and management for the survival of the last great apes should be performed with an open mind, since various pathogens with distinct characteristics in epidemiology and pathogenicity may impact the populations. An animal mortality monitoring network covering the entire African tropical forest, with the dual aims of preventing both great ape extinction and human disease outbreaks, will create necessary baseline data for such risk assessments and management plans. Copyright 2006 Wiley-Liss, Inc.

Crystallographic studies of the anthrax lethal toxin. Final report, 1 July 1994-31 December 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frederick, C.A.

1997-01-01

Protective Antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthraces, the organism responsible for anthrax. Following proteolytic activation on the host cell surface, PA forms a membrane-inserting heptamer that translocates the toxic enzymes into the cytosol. We have solved the crystal structure of monomeric PA at 2.1 A resolution and the water-soluble heptamer at 4.5 A resolution. The monomer is organized mainly into antiparallel b-sheets and has four domains: an N-terminal domain containing two calcium ions; a heptamerization domain containing a large flexible loop implicated in membrane insertion; a small domain of unknown function;more » and a C-terminal receptor-binding domain. Removal of a 20 kDa fragment from the N-terminal domain permits assembly of the heptamer, a ring-shaped structure with a negatively charged lumen, and exposes a large hydrophobic surface for binding the toxic enzymes. We present a model of pH-dependent membrane insertion involving formation of a porin-like membrane-spanning b barrel. These studies greatly enhance current understanding of the mechanism of anthrax intoxication, and will be useful in the design of recombinant anthrax vaccines.« less

A poster of pustules: representations of early twentieth century industrial anthrax in Britain.

PubMed

Stark, James F

2011-03-01

In the decades around 1900, industrial anthrax attracted significant attention from medical practitioners, legislators and the general public in Britain. Attempts to reduce the incidence of the disease ranged from basic health measures - preventing workmen from eating inside factories and trialling the use of respirators - through to national legislation making disinfection of dangerous materials mandatory. Another effort involved the production of industrial warning posters (or cautionary notices) which were designed for use in the factory environment. In the case of anthrax, the context in which these notices appeared adds to our understanding of not only the disease itself, but also the relations between those producing such posters and those who encountered them in an industrial setting. Copyright © 2010 Elsevier Ltd. All rights reserved.

Potentiation of an anthrax DNA vaccine with electroporation.

PubMed

Luxembourg, A; Hannaman, D; Nolan, E; Ellefsen, B; Nakamura, G; Chau, L; Tellez, O; Little, S; Bernard, R

2008-09-19

DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.

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

PubMed

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

2015-07-01

Although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. Here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (AICT). The AICT detects the protective antigen (PA) component of the anthrax toxin present within the blood of an animal that has died from anthrax. The test provides a result in 15min and offers the advantage of avoiding the necessity for on-site necropsy and subsequent occupational risks and environmental contamination. The specificity of the test was determined by testing samples taken from 622 animals, not infected with Bacillus anthracis. Diagnostic sensitivity was estimated on samples taken from 58 animals, naturally infected with B. anthracis collected over a 10-year period. All samples used to estimate the diagnostic sensitivity and specificity of the AICT were also tested using the gold standard of bacterial culture. The diagnostic specificity of the test was estimated to be 100% (99.4-100%; 95% CI) and the diagnostic sensitivity was estimated to be 93.1% (83.3-98.1%; 95% CI) (Clopper-Pearson method). Four samples produced false negative AICT results. These were among 9 samples, all of which tested positive for B. anthracis by culture, where there was a time delay between collection and testing of >48h and/or the samples were collected from animals that were >48h post-mortem. A statistically significant difference (P<0.001; Fishers exact test) was found between the ability of the AICT to detect PA in samples from culture positive animals <48h post-mortem, 49 of 49, Se=100% (92.8-100%; 95% CI) compared with samples tested >48h post-mortem 5 of 9 Se=56% (21-86.3%; 95% CI) (Clopper-Pearson method). Based upon these results a post hoc cut-off for use of the AICT of 48h post-mortem was applied, Se=100% (92.8-100%; 95% CI) and Sp=100% (99.4-100%; 95% CI). The high diagnostic sensitivity and specificity and the simplicity of the AICT enables it to be used for active surveillance in areas with a history of anthrax, or used as a preliminary tool in investigating sudden, unexplained death in cattle. Copyright © 2015 Elsevier B.V. All rights reserved.

Cutaneous anthrax: an overview.

PubMed

Celia, Frank

2002-04-01

The recent acts of bioterrorism have raised new questions about this uncommon disease. Clinicians are puzzled as to why some of the victims exposed to Bacillus anthracis spores developed the cutaneous form of the disease and others the inhalational form. Despite these questions, cutaneous anthrax remains relatively simple to treat effectively. The real clinical challenge lies in the diagnosis, especially being able to distinguish it from a spider bite.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Anthrax; carcasses not to be eviscerated; disposition of affected carcasses; hides, hoofs, horns, hair, viscera and contents, and fat; handling of blood and scalding vat water; general cleanup and disinfection. 310.9 Section 310.9 Animals and Animal Products FOOD SAFETY AND INSPECTION...

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

PubMed

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.

Field Management of Chemical Casualties Handbook, Second Edition

DTIC Science & Technology

2000-07-01

Treatment of disease: none, other than supportive care. Tularemia Tularemia is a zoonotic , bacterial disease with a variety of clinical...chloramphenicol are other alternatives. All are effective if used early in the course of disease. Anthrax Anthrax is an acute bacterial zoonotic disease...animals (cattle, sheep , goats) and ticks. Spread by airborne dissemination of infected excreta and also by direct contact with infected animal products

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lesperance, Ann M.

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.

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

PubMed Central

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 (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 management and control strategies, including appropriate vaccination policies in Bangladesh. PMID:25101836

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 ofmore » 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, this report presents the key issues identified at the symposium.« less

A Field Investigation of Bacillus anthracis Contamination of U.S. Department of Agriculture and Other Washington, D.C., Buildings during the Anthrax Attack of October 2001

PubMed Central

Higgins, James A.; Cooper, Mary; Schroeder-Tucker, Linda; Black, Scott; Miller, David; Karns, Jeffrey S.; Manthey, Erlynn; Breeze, Roger; Perdue, Michael L.

2003-01-01

In response to a bioterrorism attack in the Washington, D.C., area in October 2001, a mobile laboratory (ML) was set up in the city to conduct rapid molecular tests on environmental samples for the presence of Bacillus anthracis spores and to route samples for further culture analysis. The ML contained class I laminar-flow hoods, a portable autoclave, two portable real-time PCR devices (Ruggedized Advanced Pathogen Identification Device [RAPID]), and miscellaneous supplies and equipment to process samples. Envelopes and swab and air samples collected from 30 locations in the metropolitan area once every three days were subjected to visual examination and DNA extraction, followed by real-time PCR using freeze-dried, fluorescent-probe-based reagents. Surface swabs and air samples were also cultured for B. anthracis at the National Veterinary Service Laboratory (NVSL) in Ames, Iowa. From 24 October 2001 to 15 September 2002, 2,092 pieces of mail were examined, 405 real-time PCR assays were performed (comprising 4,639 samples), and at the NVSL 6,275 samples were subjected to over 18,000 platings. None of the PCR assays on DNA extracted from swab and air samples were positive, but viable spores were cultured from surface swabs taken from six locations in the metropolitan area in October, November, and December 2001 and February, March, and May 2002. DNA extracted from these suspected B. anthracis colonies was positive by real-time and conventional PCRs for the lethal factor, pXO1, and for capA and vrr genes; sequence analysis of the latter amplicons indicated >99% homology with the Ames, vollum, B6273-93, C93022281, and W-21 strains of B. anthracis, suggesting they arose from cross-contamination during the attack through the mail. The RAPID-based PCR analysis provided fast confirmation of suspect colonies from an overnight incubation on agar plates. PMID:12514046

Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh.

PubMed

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.

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

PubMed

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

2016-01-01

Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important. Copyright © 2015 by The American Association of Immunologists, Inc.

SNR analysis: molecular investigation of an anthrax epidemic

PubMed Central

2010-01-01

Background In Italy, anthrax is endemic but occurs sporadically. During the summer of 2004, in the Pollino National Park, Basilicata, Southern Italy, an anthrax epidemic consisting of 41 outbreaks occurred; it claimed the lives of 124 animals belonging to different mammal species. This study is a retrospective molecular epidemiological investigation carried out on 53 isolates collected during the epidemic. A 25-loci Multiple Locus VNTR Analysis (MLVA) MLVA was initially performed to define genetic relationships, followed by an investigation of genetic diversity between epidemic strains through Single Nucleotide Repeat (SNR) analysis. Results 53 Bacillus anthracis strains were isolated. The 25-loci MLVA analysis identified all of them as belonging to a single genotype, while the SNR analysis was able to detect the existence of five subgenotypes (SGTs), allowing a detailed epidemic investigation. SGT-1 was the most frequent (46/53); SGTs 2 (4/53), 3 (1/53) 4 (1/53) and 5 (1/53) were detected in the remaining seven isolates. Conclusions The analysis revealed the prevalent spread, during this epidemic, of a single anthrax clone. SGT-1 - widely distributed across the epidemic area and present throughout the period in question - may, thus, be the ancestral form. SGTs 2, 3 and 4 differed from SGT-1 at only one locus, suggesting that they could have evolved directly from the latter during the course of this epidemic. SGT-5 differed from the other SGTs at 2-3 loci. This isolate, thus, appears to be more distantly related to SGT-1 and may not be a direct descendant of the lineage responsible for the majority of cases in this epidemic. These data confirm the importance of molecular typing and subtyping methods for in-depth epidemiological analyses of anthrax epidemics. PMID:20187980

Genotype Analysis of Bacillus anthracis Strains Circulating in Bangladesh

PubMed Central

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. PMID:27082248

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

PubMed

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.

First Case of Bioterrorism-Related Inhalational Anthrax in the United States, Palm Beach County, Florida, 2001

PubMed Central

Wiersma, Steven T.; Rosenstein, Nancy E.; Malecki, Jean M.; Shepard, Colin W.; Raghunathan, Pratima L.; Pillai, Segaran P.; Popovic, Tanja; Quinn, Conrad P.; Meyer, Richard F.; Zaki, Sharif R.; Kumar, Savita; Bruce, Sherrie M.; Sejvar, James J.; Dull, Peter M.; Tierney, Bruce C.; Jones, Joshua D.; Perkins, Bradley A.

2002-01-01

On October 4, 2001, we confirmed the first bioterrorism-related anthrax case identified in the United States in a resident of Palm Beach County, Florida. Epidemiologic investigation indicated that exposure occurred at the workplace through intentionally contaminated mail. One additional case of inhalational anthrax was identified from the index patient’s workplace. Among 1,076 nasal cultures performed to assess exposure, Bacillus anthracis was isolated from a co-worker later confirmed as being infected, as well as from an asymptomatic mail-handler in the same workplace. Environmental cultures for B. anthracis showed contamination at the workplace and six county postal facilities. Environmental and nasal swab cultures were useful epidemiologic tools that helped direct the investigation towards the infection source and transmission vehicle. We identified 1,114 persons at risk and offered antimicrobial prophylaxis. PMID:12396910

Medical Readiness of the Reserve Component

DTIC Science & Technology

2012-01-01

once per season) (DoDI 6025.19), whereas others (such as rabies and typhoid ) are service- and/or occupation-specific. 6 For management of risks...gender-specific tests and track only the military protective mask corrective insert. Some requirements, such as for anthrax, smallpox, and yellow fever ...occupational hazards (e.g., rabies, typhoid , hepatitis B) or for a specific planned operation due to the location or threat (e.g., anthrax, smallpox

Building Civilian-Military Collaboration to Enhance Response Following an Anthrax Release

DTIC Science & Technology

2012-05-04

thought that rural communities are not considered ―high risk‖ for the anthrax scenario as their widely dispersed population may not be a likely a...terrorist target.27 The community planners’ perception of risk will impact the time and effort a rural community places towards planning for these...types of scenarios. The diversity of urban and rural populations and their differing healthcare systems and infrastructures present complexities when

Gram-positive Rod Surveillance for Early Anthrax Detection

PubMed Central

Begier, Elizabeth M.; Barrett, Nancy L.; Mshar, Patricia A.; Johnson, David G.

2005-01-01

Connecticut established telephone-based gram-positive rod (GPR) reporting primarily to detect inhalational anthrax cases more quickly. From March to December 2003, annualized incidence of blood isolates was 21.3/100,000 persons; reports included 293 Corynebacterium spp., 193 Bacillus spp., 73 Clostridium spp., 26 Lactobacillus spp., and 49 other genera. Around-the-clock GPR reporting has described GPR epidemiology and enhanced rapid communication with clinical laboratories. PMID:16229790

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

DTIC Science & Technology

2009-12-01

reviews . Finally, a gap analysis aids in explaining continued reliance on the old vaccine technology. To conclude... review of the writings on anthrax vaccine summarizes published sources and synthesizes a pattern, or shift, in the literature around the 1998 time...IOM, 2002, p. 208). A 2000 IOM report also determined, “there is a paucity of published peer- reviewed literature on the

Multiagent Vaccines Vectored by Venezuelan Equine Encephalitis Virus Replicon Elicits Immune Responses to Marburg Virus and Protection Against Anthrax and Botulinum Neurotoxin in Mice

DTIC Science & Technology

2006-01-01

and protection against anthrax and botulinum neurotoxin in mice John S. Lee a,∗, Jennifer L. Groebner a, Angela G. Hadjipanayis a,1, Diane L. Negley a...botulinum. Vaccine 24:6886 - 6892 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Lee, JS Groebner , JL Hadjipanayis

Treatment of Experimental Anthrax with Recombinant Capsule Depolymerase

DTIC Science & Technology

2007-12-01

infected with Cryptococcus neoformans (15), and the recent work of Mushtaq et al. demonstrated that a capsule-degrading endosialidase could be used to...treatment to remove microbial capsules has been suc- cessfully used to treat existing infections with pneumococci, Cryptococcus , and E. coli (2, 15, 31) in...macrophage sensitivity and resistance to anthrax lethal toxin. Infect. Immun. 61:245–252. 15. Gadebusch, H. H. 1960. Specific degradation of Cryptococcus

Operational Evaluation of the Rapid Viability PCR Method for ...

EPA Pesticide Factsheets

Journal Article This research work has a significant impact on the use of the RV-PCR method to analyze post-decontamination environmental samples during an anthrax event. The method has shown 98% agreement with the traditional culture based method. With such a success, this method, upon validation, will significantly increase the laboratory throughput/capacity to analyze a large number of anthrax event samples in a relatively short time.

Anthrax vaccine powder formulations for nasal mucosal delivery.

PubMed

Jiang, Ge; Joshi, Sangeeta B; Peek, Laura J; Brandau, Duane T; Huang, Juan; Ferriter, Matthew S; Woodley, Wendy D; Ford, Brandi M; Mar, Kevin D; Mikszta, John A; Hwang, C Robin; Ulrich, Robert; Harvey, Noel G; Middaugh, C Russell; Sullivan, Vincent J

2006-01-01

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

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

PubMed

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

2014-04-20

In concern with frequent recurrence of anthrax in endemic areas and inadvertent use of its spores as biological weapon, the development of an effective anthrax vaccine suitable for both human and veterinary needs is highly desirable. A simple oral delivery through expression in plant system could offer promising alternative to the current methods that rely on injectable vaccines extracted from bacterial sources. In the present study, we have expressed protective antigen (PA) gene in Indian mustard by Agrobacterium-mediated transformation and in tobacco by plastid transformation. Putative transgenic lines were verified for the presence of transgene and its expression by molecular analysis. PA expressed in transgenic lines was biologically active as evidenced by macrophage lysis assay. Intraperitoneal (i.p.) and oral immunization with plant PA in murine model indicated high serum PA specific IgG and IgA antibody titers. PA specific mucosal immune response was noted in orally immunized groups. Further, antibodies indicated lethal toxin neutralizing potential in-vitro and conferred protection against in-vivo toxin challenge. Oral immunization experiments demonstrated generation of immunoprotective response in mice. Thus, our study examines the feasibility of oral PA vaccine expressed in an edible plant system against anthrax. Copyright © 2014 Elsevier B.V. All rights reserved.

Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.

PubMed

Peachman, Kristina K; Li, Qin; Matyas, Gary R; Shivachandra, Sathish B; Lovchik, Julie; Lyons, Rick C; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

2012-01-01

In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.

Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity.

PubMed Central

Turnbull, P C; Broster, M G; Carman, J A; Manchee, R J; Melling, J

1986-01-01

A competitive inhibition enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies in serum to the protective antigen (PA) and lethal factor (LF) components of anthrax toxin. Current human vaccination schedules with an acellular vaccine induce predictable and lasting antibody titers to PA and, when present in the vaccine, to LF. Live spore vaccine administered to guinea pigs in a single dose conferred significantly better protection than the human vaccines (P less than 0.001), although they elicited significantly lower (P less than 0.0005) anti-PA and anti-LF titers at time of challenge with virulent Bacillus anthracis. Substantial anti-PA and anti-LF titers may not, therefore, indicate solid protective immunity against anthrax infection. The ELISA system was also shown to be capable of detecting anti-PA and anti-LF antibodies in the sera of individuals with histories of clinical anthrax. The advantage of ELISA over the Ouchterlony gel diffusion test and indirect microhemagglutination assay are demonstrated. There was a highly significant degree of correlation between ELISA and the indirect microhemagglutination assay (P less than 0.0005); but ELISA was markedly superior in terms of reproducibility, reliability, specificity, and simplicity in performance and stability of the bound antigen. PMID:3084381

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

PubMed

Bai, Jane P F; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G

2017-03-10

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.

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

PubMed Central

Bai, Jane P. F.; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G.

2017-01-01

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. PMID:28287432

A retrospective study of anthrax on the Ghaap Plateau, Northern Cape province of South Africa, with special reference to the 2007-2008 outbreaks.

PubMed

Hassim, Ayesha; Dekker, Edgar H; Byaruhanga, Charles; Reardon, Tommy; Van Heerden, Henriette

2017-09-28

Anthrax is a zoonotic disease caused by the gram-positive, endospore-forming and soil-borne bacterium Bacillus anthracis. When in spore form, the organism can survive in dormancy in the environment for decades. It is a controlled disease of livestock and wild ungulates in South Africa. In South Africa, the two enzootic regions are the Kruger National Park and the Ghaap Plateau in the Northern Cape province. Farms on the Plateau span thousands of hectares comprising of wildlife - livestock mixed use farming. In 2007-2008, anthrax outbreaks in the province led to government officials intervening to aid farmers with control measures aimed at preventing further losses. Because of the ability of the organism to persist in the environment for prolonged periods, an environmental risk or isolation survey was carried out in 2012 to determine the efficacy of control measures employed during the 2007-2008, anthrax outbreaks. No B. anthracis could be isolated from the old carcass sites, even when bone fragments from the carcasses were still clearly evident. This is an indication that the control measures and protocols were apparently successful in stemming the continuity of spore deposits at previously positive carcass sites.

Liberty to decide on dual use biomedical research: an acknowledged necessity.

PubMed

Keuleyan, Emma

2010-03-01

Humanity entered the twenty-first century with revolutionary achievements in biomedical research. At the same time multiple "dual-use" results have been published. The battle against infectious diseases is meeting new challenges, with newly emerging and re-emerging infections. Both natural disaster epidemics, such as SARS, avian influenza, haemorrhagic fevers, XDR and MDR tuberculosis and many others, and the possibility of intentional mis-use, such as letters containing anthrax spores in USA, 2001, have raised awareness of the real threats. Many great men, including Goethe, Spinoza, J.B. Shaw, Fr. Engels, J.F. Kennedy and others, have recognized that liberty is also a responsibility. That is why the liberty to decide now represents an acknowledged necessity: biomedical research should be supported, conducted and published with appropriate measures to prevent potential "dual use". Biomedical scientists should work according to the ethical principles of their Code of Conduct, an analogue of Hippocrates Oath of doctors; and they should inform government, society and their juniors about the problem. National science consulting boards of experts should be created to prepare guidelines and control the problem at state level. An international board should develop minimum standards to be applicable by each country. Bio-preparedness is considered another key-measure.

Development of a matrix to evaluate the threat of biological agents used for bioterrorism.

PubMed

Tegnell, A; Van Loock, F; Baka, A; Wallyn, S; Hendriks, J; Werner, A; Gouvras, G

2006-10-01

Adequate public health preparedness for bioterrorism includes the elaboration of an agreed list of biological and chemical agents that might be used in an attack or as threats of deliberate release. In the absence of counterterrorism intelligence information, public health authorities can also base their preparedness on the agents for which the national health structures would be most vulnerable. This article aims to describe a logical method and the characteristics of the variables to be brought in a weighing process to reach a priority list for preparedness. The European Union, in the aftermath of the anthrax events of October 2001 in the United States, set up a task force of experts from multiple member states to elaborate and implement a health security programme. One of the first tasks of this task force was to come up with a list of priority threats. The model, presented here, allows Web-based updates for newly identified agents and for the changes occurring in preventive measures for agents already listed. The same model also allows the identification of priority protection action areas.

Rapid test for the detection of hazardous microbiological material

NASA Astrophysics Data System (ADS)

Mordmueller, Mario; Bohling, Christian; John, Andreas; Schade, Wolfgang

2009-09-01

After attacks with anthrax pathogens have been committed since 2001 all over the world the fast detection and determination of biological samples has attracted interest. A very promising method for a rapid test is Laser Induced Breakdown Spectroscopy (LIBS). LIBS is an optical method which uses time-resolved or time-integrated spectral analysis of optical plasma emission after pulsed laser excitation. Even though LIBS is well established for the determination of metals and other inorganic materials the analysis of microbiological organisms is difficult due to their very similar stoichiometric composition. To analyze similar LIBS-spectra computer assisted chemometrics is a very useful approach. In this paper we report on first results of developing a compact and fully automated rapid test for the detection of hazardous microbiological material. Experiments have been carried out with two setups: A bulky one which is composed of standard laboratory components and a compact one consisting of miniaturized industrial components. Both setups work at an excitation wavelength of λ=1064nm (Nd:YAG). Data analysis is done by Principal Component Analysis (PCA) with an adjacent neural network for fully automated sample identification.

Terrorism preparedness in state health departments--United States, 2001-2003.

PubMed

2003-10-31

The anthrax attacks in fall 2001 highlighted the role of infectious disease (ID) epidemiologists in terrorism preparedness and response. Beginning in 2002, state health departments (SHDs) received approximately 1 billion dollars in new federal funding to prepare for and respond to terrorism, infectious disease outbreaks, and other public health threats and emergencies. This funding is being used in part to improve epidemiologic and surveillance capabilities. To determine how states have used a portion of their new funding to increase ID epidemiology capacity, the Iowa Department of Public Health's Center for Acute Disease Epidemiology and the Iowa State University Department of Microbiology conducted two surveys of U.S. state epidemiologists during September 2000-August 2001 and October 2002-June 2003. This report summarizes the results of these surveys, which determined that although the number of SHD epidemiology workers assigned to ID and terrorism preparedness increased by 132%, concerns remained regarding the ability of SHDs to hire qualified personnel. These findings underscore the need to develop additional and more diverse training venues for current and future ID epidemiologists.

Responding to chemical, biological, or nuclear terrorism: the indirect and long-term health effects may present the greatest challenge.

PubMed

Hyams, Kenneth C; Murphy, Frances M; Wessely, Simon

2002-04-01

The possibility of terrorists employing chemical, biological, or nuclear/ radiological (CBN) materials has been a concern since 1995 when sarin gas was dispersed in a Tokyo subway. Contingency planning almost exclusively involved detection. containment, and emergency health care for mass casualties. However, it is clear that even small-scale CBN incidents--like the recent spread of anthrax spores through the mail--can cause widespread confusion, fear, and psychological stress that have lasting effects on the health of affected communities and on a nation's sense of well-being. More emphasis therefore needs to be placed on indirect effects and on the medical, social, economic, and legal consequences that follow months to years afterward. To respond effectively to CBN attacks, a comprehensive strategy needs to be developed that includes not only emergency response, but also long-term health care, risk communication, research, and economic assistance. Organizing an effective response challenges government institutions because the issues involved--eligibility for health care, the effects of low-level exposure to toxic agents. stress-related illnesses, unlicensed therapeutics. financial compensation--are complex and controversial.

Did Michelangelo Have Gout?

PubMed

Pinals, Robert S; Schlesinger, Naomi

2015-10-01

Michelangelo, the great Renaissance artist, is often included on lists of celebrated gout patients. His letters describe a single acute attack of foot pain at the age of 80, but a case for early onset has been presented, based on a fresco by a contemporary artist, Raphael. A figure resembling Michelangelo at the age of 36 appears to have nodules resembling tophi over his knees.In this report, we review Michelangelo's medical history, discuss the proposal that he had tophaceous gout, and address the significance of "knobby" knees in his works and those of other artists.

Historical Data Analysis of Hospital Discharges Related to the Amerithrax Attack in Florida

PubMed Central

Burke, Lauralyn K.; Brown, C. Perry; Johnson, Tammie M.

2016-01-01

Interrupted time-series analysis (ITSA) can be used to identify, quantify, and evaluate the magnitude and direction of an event on the basis of time-series data. This study evaluates the impact of the bioterrorist anthrax attacks (“Amerithrax”) on hospital inpatient discharges in the metropolitan statistical area of Palm Beach, Broward, and Miami-Dade counties in the fourth quarter of 2001. Three statistical methods—standardized incidence ratio (SIR), segmented regression, and an autoregressive integrated moving average (ARIMA)—were used to determine whether Amerithrax influenced inpatient utilization. The SIR found a non–statistically significant 2 percent decrease in hospital discharges. Although the segmented regression test found a slight increase in the discharge rate during the fourth quarter, it was also not statistically significant; therefore, it could not be attributed to Amerithrax. Segmented regression diagnostics preparing for ARIMA indicated that the quarterly data time frame was not serially correlated and violated one of the assumptions for the use of the ARIMA method and therefore could not properly evaluate the impact on the time-series data. Lack of data granularity of the time frames hindered the successful evaluation of the impact by the three analytic methods. This study demonstrates that the granularity of the data points is as important as the number of data points in a time series. ITSA is important for the ability to evaluate the impact that any hazard may have on inpatient utilization. Knowledge of hospital utilization patterns during disasters offer healthcare and civic professionals valuable information to plan, respond, mitigate, and evaluate any outcomes stemming from biothreats. PMID:27843420

Application of Pyrosequencing® in Food Biodefense.

PubMed

Amoako, Kingsley Kwaku

2015-01-01

The perpetration of a bioterrorism attack poses a significant risk for public health with potential socioeconomic consequences. It is imperative that we possess reliable assays for the rapid and accurate identification of biothreat agents to make rapid risk-informed decisions on emergency response. The development of advanced methodologies for the detection of biothreat agents has been evolving rapidly since the release of the anthrax spores in the mail in 2001, and recent advances in detection and identification techniques could prove to be an essential component in the defense against biological attacks. Sequence-based approaches such as Pyrosequencing(®), which has the capability to determine short DNA stretches in real time using biotinylated PCR amplicons, have potential biodefense applications. Using markers from the virulence plasmids and chromosomal regions, my laboratory has demonstrated the power of this technology in the rapid, specific, and sensitive detection of B. anthracis spores and Yersinia pestis in food. These are the first applications for the detection of the two organisms in food. Furthermore, my lab has developed a rapid assay to characterize the antimicrobial resistance (AMR) gene profiles for Y. pestis using Pyrosequencing. Pyrosequencing is completed in about 60 min (following PCR amplification) and yields accurate and reliable results with an added layer of confidence, thus enabling rapid risk-informed decisions to be made. A typical run yields 40-84 bp reads with 94-100 % identity to the expected sequence. It also provides a rapid method for determining the AMR profile as compared to the conventional plate method which takes several days. The method described is proposed as a novel detection system for potential application in food biodefense.

Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

DTIC Science & Technology

2005-08-04

inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and...fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7–8 using trehalose as stabilizer and a CpG...gas- trointestinal, and pulmonary routes. The inhaled form is of particular concern considering its de- monstrated use as a bioweapon.1–4 Inhalational

Pulmonary Anthrax Caused by Contaminated Sacks

PubMed Central

Enticknap, J. B.; Galbraith, N. S.; Tomlinson, A. J. H.; Elias-Jones, T. F.

1968-01-01

A 54-year-old Jamaican employed as a grinding machine operator developed pulmonary anthrax and died within two days. In the eight days before his illness he had been grinding sterilized bone charcoal delivered in second-hand sacks, some of which had been used to import the raw bone before its sterilization. Bacillus anthracis was isolated from four out of six sacks examined and is considered to have been the source of the infection. PMID:4966788

Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

DTIC Science & Technology

2005-02-15

29. Horwitz, M. A. 1984. Phagocytosis of the Legionnaires ’ disease bacterium (Le- gionella pneumophila) occurs by a novel mechanism: engulfment within...Journal of Immunology, 2005, 174: 5545–5552. I nhalational anthrax, a disease that was exploited for bioter-rorism (1), is most often fatal and causes...them out of the lungs. However, mice that were chemically depleted of macrophages and infected with spores by aerosol nev- ertheless experienced disease

Economic Impacts of a Wide Area Release of Anthrax

DOE Office of Scientific and Technical Information (OSTI.GOV)

Judd, Kathleen S.; Olson, Jarrod; Stein, Steven L.

2009-05-29

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

[Sacer ignis, quam pustulam vocant pastores: anthrax--cultural historical traces of a zoonosis].

PubMed

Eitel, J

2003-01-01

The knowledge of anthrax as a disease and its importance as a zoonosis in the Greco-Roman world is revealed through a selection of classical texts and mythological sources, taking into account evidence of reworking and reuse of these texts up until the nineteenth century. The numerous names given to the disease throughout history and their linguistic origins will also be examined in this paper. The narrative of the epizoonoses in Noricum in Virgil's Georgics; taken by several to represent a description of an anthrax epidemic, and which had a great influence in written works on veterinary medicine up until the discovery of bacteria, will be given particular attention. The crucial term is "Sacer Ignis", synonymous for several different human and animal diseases through time. This term will be analysed in terms of linguistic origin and the changes in meaning it acquired throughout the centuries.

Effect of endosomal acidification on small ion transport through the anthrax toxin PA63 channel.

PubMed

Kalu, Nnanya; Alcaraz, Antonio; Yamini, Goli; Momben Abolfath, Sanaz; Lucas, Laura; Kenney, Clare; Aguilella, Vicente M; Nestorovich, Ekaterina M

2017-11-01

Tight regulation of pH is critical for the structure and function of cells and organelles. The pH environment changes dramatically along the endocytic pathway, an internalization transport process that is 'hijacked' by many intracellularly active bacterial exotoxins, including the anthrax toxin. Here, we investigate the role of pH on single-channel properties of the anthrax toxin protective antigen (PA 63 ). Using conductance and current noise analysis, blocker binding, ion selectivity, and poly(ethylene glycol) partitioning measurements, we show that the channel exists in two different open states ('maximum' and 'main') at pH ≥ 5.5, while only a maximum conductance state is detected at pH < 5.5. We describe two substantially distinct patterns of PA 63 conductance dependence on KCl concentration uncovered at pH 6.5 and 4.5. © 2017 Federation of European Biochemical Societies.

Methods for neutralizing anthrax or anthrax spores

DOEpatents

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

2013-02-26

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

Challenges in disposing of anthrax waste.

PubMed

Lesperance, Ann M; Stein, Steve; Upton, Jaki F; Toomey, Chris

2011-09-01

Disasters often create large amounts of waste that must be managed as part of both immediate response and long-term recovery. While many federal, state, and local agencies have debris management plans, these plans often do not address chemical, biological, and radiological contamination. The Interagency Biological Restoration Demonstration's (IBRD) purpose was to holistically assess all aspects of an anthrax incident and assist in the development of a plan for long-term recovery. In the case of wide-area anthrax contamination and the follow-on response and recovery activities, a significant amount of material would require decontamination and disposal. Accordingly, IBRD facilitated the development of debris management plans to address contaminated waste through a series of interviews and workshops with local, state, and federal representatives. The outcome of these discussions was the identification of 3 primary topical areas that must be addressed: planning, unresolved research questions, and resolving regulatory issues.

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

PubMed

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

2014-02-01

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

Challenges in Disposing of Anthrax Waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2011-09-01

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