United States' regulatory approved pharmacotherapies for nuclear reactor explosions and anthrax-associated bioterrorism.

INTRODUCTION: Nuclear reactor incidents and bioterrorism outbreaks are concerning public health disasters. Little is known about US Food and Drug Administration (FDA)-approved agents that can mitigate consequences of these events. We review FDA data supporting regulatory approvals of these agents. AREAS COVERED: We reviewed pharmaceutical products approved to treat Hematopoietic Acute Radiation Syndrome (H-ARS) and to treat or prevent pulmonary infections following Bacillus anthracis (anthrax) exposure. Four drugs were approved for H-ARS: granulocyte-colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor, pegylated G-CSF, and romiplostim. For bioterrorism-associated anthrax, the FDA approved five antibiotics (doxycycline, penicillin-G, levofloxacin, moxifloxacin, and ciprofloxacin), two monoclonal antibodies (obiltoxaximab and raxibacumab), one polyclonal antitoxin (Anthrax Immune Globulin Intravenous) and two vaccines (Anthrax Vaccine Adsorbed and Anthrax Vaccine Adsorbed with an adjuvant). A national stockpile system ensures that communities have ready access to these agents. Our literature search was based on data included in drugs@FDA (2001-2023). EXPERT OPINION: Two potential mass public health disasters are aerosolized anthrax dissemination and radiological incidents. Five agents authorized for anthrax emergencies only have FDA approval for this indication, five antibiotics have FDA approvals as antibiotics for common infections and for bacillus anthrax, and four agents have regulatory approvals for supportive care for cancer and for radiological incidents.

Construção e validação de instrumento para avaliação das medidas de biossegurança em bioterrorismo pelos bombeiros / Construction and validation of and assessment tool for biosafety measures in bioterrorism for firefighters / Construcción y validación de un instrumento para evaluar las medidas de bioseguridad en el bioterrorismo de los bomberos

Objetivo: Este estudo teve como objetivo desenvolver e validar um instrumento de avaliação das medidas de Biossegurança adotadas pelos bombeiros militares, para a contenção dos agentes biológicos frente a um evento de bioterrorismo. Métodos: Tratou-se de um estudo descritivo de abordagem quantitativa, de desenvolvimento metodológico e do tipo de validação de conteúdo de um instrumento de avaliação. O estudo foi dividido nas fases de desenvolvimento e validação do instrumento. Para o desenvolvimento do instrumento foram feitas revisões da literatura e para a validação do instrumento foi utilizado o método Delphi. Para o estudo foram incluídos 6 juízes que avaliaram o instrumento através da escala numérica tipo Likert. Resultados: Os juízes avaliaram que o instrumento proposto está bem estruturado, possuindo boa clareza e coesão de escrita, com aplicabilidade no campo de estudo e de grande relevância, principalmente em vista a ausência desse tipo de instrumento para a população de bombeiros militares. Para avaliar a concordância entre os juízes foi utilizado o índice de Validade de Conteúdo, que alcançou 98% de concordância e o Índice de Fidedignidade Interavaliadores, que alcançou os conceitos bom e muito bom, mostrando baixa variância das respostas dos juízes, sendo estatisticamente válido. Conclusão: O estudo descreveu o processo de construção e validação do instrumento, provando ser apropriado e confiável para ser utilizado.

Objective: This study aimed to develop and validate an instrument to assess the Biosafety measures adopted by firefighters, for the containment of biological agents in the face of a bioterrorism event. Methods: This is a descriptive study with a quantitative approach, methodological development, and the type of content validation of an assessment instrument. The study was divided into instrument development and validation phases. For the development of the instrument, literature reviews were conducted and for the instrument validation, the Delphi method was used. For the study, 6 judges were included who evaluated the instrument using the Likert-type numerical scale. Results: The judges evaluated that the proposed instrument is well structured, with good clarity and cohesion of writing, with applicability in the field of study and of great relevance, especially considering the absence of this type of instrument for the military firefighter population. To evaluate the agreement between the judges, we used the Content Validity Index which reached 98% of agreement and the Interrate agreement, which reached the concepts good and very good, showing low variance of the judges' answers, being statistically valid. Conclusion: The study described the process of construction and validation of the instrument, proving to be appropriate and reliable to be used.

Objetivo: Este estudio tenía como objetivo desarrollar y validar un instrumento para evaluar las medidas de bioseguridad adoptadas por los bomberos militares para contener los agentes biológicos durante un evento de bioterrorismo. Métodos: Se trata de un estudio descriptivo de abordaje cuantitativo, de desarrollo metodológico y del tipo de validación de contenido de un instrumento de evaluación. El estudio se dividió en las fases de desarrollo y validación del instrumento. Para la elaboración del instrumento se realizaron revisiones bibliográficas y para la validación del mismo se utilizó el método Delphi. Para el estudio se incluyeron 6 jueces que evaluaron el instrumento mediante una escala numérica tipo Likert. Resultados: Los jueces evaluaron que el instrumento propuesto está bien estructurado, poseyendo buena claridad y cohesión de redacción, con aplicabilidad en el campo de estudio y de gran relevancia, especialmente en vista de la ausencia de este tipo de instrumento para la población de bomberos militares. Se utilizó el Índice de Validez de Contenido para evaluar la concordancia entre los jueces, alcanzando un 98% de acuerdo y el Índice de Fiabilidad Inter-registrador, que alcanzó conceptos buenos y muy buenos, mostrando una baja varianza en las respuestas de los jueces, siendo estadísticamente válido. Conclusión: El estudio describió el proceso de construcción y validación del instrumento, demostrando ser apropiado y confiable para ser utilizado.

An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications.

INTRODUCTION: Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in a smallpox outbreak. While there has not been a reported case of smallpox since 1978 it is still considered a serious bioterrorism threat. AREAS COVERED: A brief history of smallpox from its proposed origins as a human disease through its eradication in the late 20th century is presented. The current smallpox threat and the current public health response plans are described. The discovery, and development of tecovirimat through NDA submission and subsequent approval for treatment of smallpox are discussed. Google Scholar and PubMed were searched over all available dates for relevant publications. EXPERT OPINION: Approval of tecovirimat to treat smallpox represents an important milestone in biosecurity preparedness. Incorporating tecovirimat into the CDC smallpox response plan, development of pediatric liquid and intravenous formulations, and approval for post-exposure prophylaxis would provide additional health security benefit.Tecovirimat shows broad efficacy against orthopoxviruses in vitro and in vivo and could be developed for use against emerging orthopoxvirus diseases such as monkeypox, vaccination-associated adverse events, and side effects of vaccinia oncolytic virus therapy.

Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry.

Some pathogens and toxins have the potential to be used as weapons of mass destruction and instigate population-based fear. Efforts to mitigate biothreat require development of efficient countermeasures which in turn relies on fast and accurate methods to detect the biological agents in a range of complex matrices including environmental and clinical samples. We report here an mass spectrometry (MS) based methodology, employing both targeted and shot-gun approaches for the verification of biological agents from the environmental samples. Our shot-gun methodology relied on tandem MS analysis of abundant peptides from the spiked samples, whereas, the targeted method was based on an extensive elucidation of marker proteins and unique peptides resulting in the generation of an inclusion list of masses reflecting relevant peptides for the unambiguous identification of nine bacterial species [listed as priority agents of bioterrorism by Centre for Disease Control and Prevention (CDC)] belonging to phylogenetically diverse genera. The marker peptides were elucidated by extensive literature mining, in silico analysis, and tandem MS (MS/MS) analysis of abundant proteins of the cultivated bacterial species in our laboratory. A combination of shot-gun MS/MS analysis and the targeted search using a panel of unique peptides is likely to provide unambiguous verification of biological agents at sub-species level, even with limited fractionation of crude protein extracts from environmental samples. The comprehensive list of peptides reflected in the inclusion list, makes a valuable resource for the multiplex analysis of select biothreat agents and further development of targeted MS/MS assays.

A lanthanide-based magnetic nanosensor as an erasable and visible platform for multi-color point-of-care detection of multiple targets and the potential application by smartphone.

The sensitive, selective and point-of-care detection of dipicolinic acid (DPA) is of great significance for the prevention of the anthrax virus and the containment of bioterrorism. In this work, a multi-color fluorescent nanoprobe composed of lanthanides and magnetic nanoparticles (Fe3O4@CePO4:Tb-EDTA-Eu) has been designed, in which the portion of Fe3O4@CePO4:Tb can be used as the internal stable signal of green fluorescence, while the EDTA-Eu part can be used as the sensitive reaction signal for monitoring DPA. Upon the addition of DPA, the red fluorescence of Eu3+ ions is significantly enhanced, while the fluorescent color of the nanoprobes can change from green to red (such as yellow-green, orange-yellow and orange-red), achieving visual multi-color fluorescent detection even by the naked eye. By using the magnetic separation method, the composites can be easily purified for point-of-care testing. More importantly, the nanoprobe fixed test pieces enable real-time analysis of DPA by using an easy-to-access color-scanning application on a smartphone. Furthermore, the fluorescence intensity can be quenched by the addition of Cu2+, which leads to a rewritable nanosensor and can be used in the detection of cysteine (Cys) with high sensitivity. With the addition of Cys, this erasable nano detection platform can also display the original multi-color visual point-of-care detection. With further optimization, this new type of multi-color fluorescent assay is promising in point-of-care clinics for multi-target diagnostics.

Dissection of the molecular circuitry controlling virulence in Francisella tularensis.

Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, F. tularensis is classified as a category A bioweapon by the US government. F. tularensis virulence stems from genes encoded on the Francisella pathogenicity island (FPI). An unusual set of Francisella regulators-the heteromeric macrophage growth locus protein A (MglA)-stringent starvation protein A (SspA) complex and the DNA-binding protein pathogenicity island gene regulator (PigR)-activates FPI transcription and thus is essential for virulence. Intriguingly, the second messenger, guanosine-tetraphosphate (ppGpp), which is produced during infection, is also involved in coordinating Francisella virulence; however, its role has been unclear. Here we identify MglA-SspA as a novel ppGpp-binding complex and describe structures of apo- and ppGpp-bound MglA-SspA. We demonstrate that MglA-SspA, which binds RNA polymerase (RNAP), also interacts with the C-terminal domain of PigR, thus anchoring the (MglA-SspA)-RNAP complex to the FPI promoter. Furthermore, we show that MglA-SspA must be bound to ppGpp to mediate high-affinity interactions with PigR. Thus, these studies unveil a novel pathway different from those described previously for regulation of transcription by ppGpp. The data also indicate that F. tularensis pathogenesis is controlled by a highly interconnected molecular circuitry in which the virulence machinery directly senses infection via a small molecule stress signal.

Federal Funding for Health Security in FY2016.

This article assesses US government funding in 5 domains critical to strengthening health security: biodefense programs, radiological and nuclear programs, chemical programs, pandemic influenza and emerging infectious disease programs, and multiple-hazard and preparedness programs. This year's article also highlights the emergency funding appropriated in FY2015 to enable the international and domestic response to the Ebola outbreak in West Africa.

Potential biodefense model applications for portable chlorine dioxide gas production.

Development of decontamination methods and strategies to address potential infectious disease outbreaks and bioterrorism events are pertinent to this nation's biodefense strategies and general biosecurity. Chlorine dioxide (ClO2) gas has a history of use as a decontamination agent in response to an act of bioterrorism. However, the more widespread use of ClO2 gas to meet current and unforeseen decontamination needs has been hampered because the gas is too unstable for shipment and must be prepared at the application site. Newer technology allows for easy, onsite gas generation without the need for dedicated equipment, electricity, water, or personnel with advanced training. In a laboratory model system, 2 unique applications (personal protective equipment [PPE] and animal skin) were investigated in the context of potential development of decontamination protocols. Such protocols could serve to reduce human exposure to bacteria in a decontamination response effort. Chlorine dioxide gas was capable of reducing (2-7 logs of vegetative and spore-forming bacteria), and in some instances eliminating, culturable bacteria from difficult to clean areas on PPE facepieces. The gas was effective in eliminating naturally occurring bacteria on animal skin and also on skin inoculated with Bacillus spores. The culturable bacteria, including Bacillus spores, were eliminated in a time- and dose-dependent manner. Results of these studies suggested portable, easily used ClO2 gas generation systems have excellent potential for protocol development to contribute to biodefense strategies and decontamination responses to infectious disease outbreaks or other biothreat events.

Bioterrorismo, riscos biológicos e as medidas de biossegurança aplicáveis ao Brasil / Bioterrorism, biological risks and biosafety measures applicable to Brazil

A história registra o uso de patógenos como potencializadores de recursos bélicos. Considerando os eventos bélicos da contemporaneidade, observa-se a formulação de projetos voltados para elaboração tecnológica sofisticada. Nessa categoria se incluem as armas biológicas, vinculadas aos programas de caráter coercitivo conhecidos como guerras biológicas, que pertencem à lógica da ameaça assimétrica, não definindo território e gerando repercussões econômicas, políticas e sociopsicológicas devastadoras. Esses eventos demandam a elaboração de planos que contemplem o risco, incluindo a capacitação de recursos humanos, investimentos na identificação de materiais empregados em bioterrorismo e também em equipamentos de segurança. Objetiva-se neste artigo discutir a associação entre patógenos, seu potencial de risco e eficácia para o emprego em estratégias de bioterrorismo, destacando as medidas de biossegurança necessárias. Utiliza-se a revisão integrativa para a construção de análises de contextos de risco. O levantamento bibliográfico compreendeu o período 1990/2010, nas bases de dados ISI, LILACS, SciELO e PubMed. Demonstra-se a importância do envolvimento e da capacitação dos profissionais na identificação de agentes biológicos com potencial de risco, considerando que o bioterrorismo pode resultar na sobrecarga dos sistemas de saúde. A biossegurança orienta os procedimentos que devem ser adotados para a contenção dos patógenos, visando ao controle dos riscos...

History records the use of pathogens as improvers of military resources. Considering the events of contemporary war, there is the formulation of projects aimed at sophisticated technological development. They shall include biological weapons, linked to coercive programs known as biological warfare, which belong to the logic of asymmetric threat, not defining territory and generating devastating economic, political and socio-psychological repercussions. These events require the preparation of plans that address the risk, including the training of human resources, investments in the identification of materials used in bioterrorism and also in safety equipment. This paper aims to discuss the association between pathogens, their potential risk and effectiveness for use in bioterrorism strategies, highlighting the necessary biosecurity measures. It uses an integrative review to construct contexts risk analysis. The literature included the period 1990/2010, the ISI databases, LILACS, SciELO and PubMed. It demonstrates the importance of the involvement and training of professionals in the identification of biological agents with potential risk, whereas bioterrorism may result in overload of health systems. Biosecurity guides the procedures to be adopted for the containment of pathogens, aimed at controlling risk...

Targeting ricin to the ribosome.

The plant toxin ricin is highly toxic for mammalian cells and is of concern for bioterrorism. Ricin belongs to a family of functionally related toxins, collectively referred to as ribosome inactivating proteins (RIPs), which disable ribosomes and halt protein synthesis. Currently there are no specific antidotes against ricin or related RIPs. The catalytic subunit of ricin is an N-glycosidase that depurinates a universally conserved adenine residue within the sarcin/ricin loop (SRL) of the 28S rRNA. This depurination activity inhibits translation and its biochemistry has been intensively studied. Yet, recent developments paint a more complex picture of toxicity, with ribosomal proteins and cellular signaling pathways contributing to the potency of ricin. In particular, several studies have now established the importance of the ribosomal stalk structure in facilitating the depurination activity and ribosome specificity of ricin and other RIPs. This review highlights recent developments defining toxin-ribosome interactions and examines the significance of these interactions for toxicity and therapeutic intervention.

A method to characterise site, urban and regional ambient background radiation.

Control dosemeters are routinely provided to customers to monitor the background radiation so that it can be subtracted from the gross response of the dosemeter to arrive at the occupational dose. Landauer, the largest dosimetry processor in the world with subsidiaries in Australia, Brazil, China, France, Japan, Mexico and the UK, has clients in approximately 130 countries. The Glenwood facility processes over 1.1 million controls per year. This network of clients around the world provides a unique ability to monitor the world's ambient background radiation. Control data can be mined to provide useful historical information regarding ambient background rates and provide a historical baseline for geographical areas. Historical baseline can be used to provide site or region-specific background subtraction values, document the variation in ambient background radiation around a client's site or provide a baseline for measuring the efficiency of clean-up efforts in urban areas after a dirty bomb detonation.

Lack of strategic insight: the "dirty bomb" effort.

Multiple countries including the United States and France are investing heavily in countermeasures to the threat of a "dirty bomb." All of the machinery simply involves a variation on a Geiger counter that picks up excess photon irradiation. Classically, a "dirty bomb" is defined as a dangerous radioactive material mixed in a variety of ways with high explosive, so when detonated, radioactive material is dispersed. Solid radioactive material such as Cesium or Cobalt sends off very penetrating ('hard') photons from which one cannot simply be protected by sheet lead or a heavy door. For official occasions with dignitaries of State, such a bomb could prove a modest distraction, but simple radiation physics suggests such a bomb would be limited in the damage it could cause, would largely be a mess to be cleaned up by an appropriately trained crew, would involve a very confined area, and thoroughly fails to comprehend the mentality of al-Queda 'central' that wishes to follow 9/11 with an equal or greater show of terrorist force. The author would argue this sort of mind-think occurs when you have too few people in the hard sciences in your intelligence sections.

Requirements for estimation of doses from contaminants dispersed by a 'dirty bomb' explosion in an urban area.

The ARGOS decision support system is currently being extended to enable estimation of the consequences of terror attacks involving chemical, biological, nuclear and radiological substances. This paper presents elements of the framework that will be applied in ARGOS to calculate the dose contributions from contaminants dispersed in the atmosphere after a 'dirty bomb' explosion. Conceptual methodologies are presented which describe the various dose components on the basis of knowledge of time-integrated contaminant air concentrations. Also the aerosolisation and atmospheric dispersion in a city of different types of conceivable contaminants from a 'dirty bomb' are discussed.

Essential veterinary education in food safety, food hygiene and biosecurity: a global perspective.

A big challenge for veterinary educators is to stimulate interest in public health medicine and make the curriculum interesting, and relevant, to veterinary students. Veterinary public health encompasses many areas, including zoonosis control, food safety, animal health and biosecurity, animals as sentinels of environmental hazards and the contribution of animal waste to pollution of food and water, so there is no shortage of ammunition for the veterinary educator in the competition for students' attention. Veterinary educators, not the students, will have failed if graduates complete their studies without being convinced of the importance and relevance of veterinary public health.

Overview of the inactivation by 254 nm ultraviolet radiation of bacteria with particular relevance to biodefense.

Our goal was to ultimately predict the sensitivity of untested bacteria (including those of biodefense interest) to ultraviolet (UV) radiation. In this study, we present an overview and analysis of the relevant 254 nm data previously reported and available in the literature. The amount of variability in this data prevented us from determining an "average" response for any bacterium. Therefore, we developed particular selection criteria to include the data in our analysis and suggested future guidelines for reporting UV sensitivity results. We then compiled a table of the sensitivity to 254 nm UV for 38 bacteria and three bacterial spores. The UV sensitivity was quite similar (within 10%) among the spores of Bacillus anthracis (strains Vollum 1B and Sterne), Bacillus subtilis, and Bacillus megaterium. These data indicate that spores of B. subtilis and B. megaterium could be adequate simulants of B. anthracis spores in UVC experiments. Spores of B. anthracis, B. subtilis and B. megaterium were 5-10 times more resistant to UV than were their corresponding vegetative cells. The vegetative cells of B. anthracis showed similar UV sensitivity to those of Burkholderia pseudomallei, Shigella sonnei, and a wild-type strain of Escherichia coli. Yersinia enterocolitica and Vibrio cholerae appeared more sensitive to UV and Salmonella typhi slightly more resistant to UV than E. coli. The sensitivity (at 254 nm) of all vegetative bacteria ranged from 11 to 80 Jm(2) for a 1 Log(10) kill and from 25-200 Jm(2) for 4 Log(10) kill.

Bioterrorism: class A agents and their potential presentations in immunocompromised patients.

A bioterrorism attack would be particularly challenging for medical professionals caring for patients with cancer who often have weakened immune systems. Knowledge of the class A agents and the potential variable presentations in immunocompromised patients is key to early recognition of an outbreak and prompt reporting. The purpose of this article is to present the class A agents: Bacillus anthracis (anthrax), botulinum toxin (botulism), variola virus (smallpox), Yersinia pestis (pneumonic plague), and Francisella tularensis (tularemia). The variable signs and symptoms that may be present in immunocompromised patients with cancer will be discussed with a focus on assessment and early recognition of an outbreak. The availability of vaccines and the implications for patients with cancer receiving these vaccines also will be discussed.

Clinical care in the "Hot Zone".

The threat of chemical, biological, radiological and nuclear incidents is unlikely to decrease and preparations to deal with this type of incident are well established in most European emergency medical systems. In the UK medical care is not currently provided in the "Hot" or contaminated zone. This article discusses the background to the current threat and suggests that, where survivors are present in the "Hot Zone", medical care should be started there to minimise delay and maximise the chances of survival.