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PubMed2006

LC16m8: an attenuated smallpox vaccine.

The frequency of moderate to severe adverse reactions associated with smallpox vaccines currently stockpiled in the US, and the continued threat of bioterrorism have prompted the development of effective vaccines with improved safety profiles. LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. It has been shown to have markedly less neurotoxicity than unattenuated vaccines in nonclinical studies. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. This article reviews the history and available scientific literature regarding LC16m8 and provides comparisons to other smallpox vaccines.

Animals↗
PubMed2004

Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin.

In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies.

Animals↗
PubMed2003

Position of the American Dietetic Association: food and water safety.

It is the position of the American Dietetic Association that the public has the right to a safe food and water supply. The Association supports collaboration among dietetics professionals, academics, representatives of the agriculture and food industries, and appropriate government agencies to ensure the safety of the food and water supply by providing education to the public and industry, promoting technologic innovation and applications, and supporting further research. Numerous bacterial, viral, and chemical food and water threats exist with certain populations such as the elderly, children, pregnant women, those in institutionalized settings, and the immune compromised being at high risk. Recent outbreaks of food and waterborne disease and threats of bioterrorism have focused attention on the safety of US food and water systems. The US government and other entities have developed programs to address challenges associated with maintaining food and water safety. Safety initiatives such as the Pathogen Reduction/Hazard Analysis Critical Point (HACCP), revisions to the Food Code, and the National Primary Drinking Water Regulations provide a framework to evaluate current and future challenges to the safety of food and water systems. Dietetics professionals should take a proactive role in ensuring that appropriate food and water safety practices are followed and can also assume major roles in food and water safety education and research.

Bioterrorism↗
PubMed2002

Smallpox and pregnancy: from eradicated disease to bioterrorist threat.

Health care personnel must be prepared for the threat of bioterrorism. Our objective is to educate primary care providers, obstetricians in particular, in the prevention, diagnosis, and treatment of smallpox. Smallpox poses a particularly serious threat because of its high case-fatality rate in unvaccinated populations (no one younger than 25 years has been vaccinated, and older persons have little remaining residual immunity). Routine nonemergency smallpox vaccination is restricted to laboratory staff working with smallpox-related viruses. Under these circumstances, contraindications to vaccination are pregnancy, immunodeficiency, exfoliative skin conditions (eczema), and allergy to vaccine components. In case of an intentional release of the smallpox virus, those directly exposed and their close contacts must be vaccinated and isolated. Under such emergency circumstances, pregnant women exposed to the variola virus should be vaccinated because of the lethality of the disease during pregnancy. Currently, there is a limited supply of vaccine available.

Adult↗
PubMedDate not supplied

Transmission of infectious diseases during commercial air travel.

Because of the increasing ease and affordability of air travel and mobility of people, airborne, food-borne, vector-borne, and zoonotic infectious diseases transmitted during commercial air travel are an important public health issue. Heightened fear of bioterrorism agents has caused health officials to re-examine the potential of these agents to be spread by air travel. The severe acute respiratory syndrome outbreak of 2002 showed how air travel can have an important role in the rapid spread of newly emerging infections and could potentially even start pandemics. In addition to the flight crew, public health officials and health care professionals have an important role in the management of infectious diseases transmitted on airlines and should be familiar with guidelines provided by local and international authorities.

Aerospace Medicine↗
PubMed2003

Carbohydrates and glycoproteins of Bacillus anthracis and related bacilli: targets for biodetection.

The spore is the form released in a bioterrorism attack. There is a real need for definition of new targets for Bacillus anthracis that might be incorporated into emerging biodetection technologies. Particularly of interest are macromolecules found in B. anthracis that are (1) spore-specific, (2) readily accessible on the spore surface and (3) distinct from those present in related organisms. One of the few biochemical methods to identify the spores of B. anthracis is based on the presence of rhamnose and 3-O-methyl rhamnose as determined by gas chromatography-mass spectrometry. Related organisms additionally contain 2-O-methyl rhamnose and fucose. Carbohydrates and glycoproteins of the B. cereus group of organisms and the related B. subilis group are reviewed here. It is hypothesized that the spore-specific carbohydrate is a component of the newly described glycoprotein of the exosporium of B. anthracis. Further work to define the protein and carbohydrate components of the glycoprotein of B. anthracis could be highly useful in developing new technologies for rapid biodetection.

Bacillus anthracis↗
PubMed2003

Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.

In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families.

Antiviral Agents↗
PubMed2003

An innovative approach to training hospital-based clinicians for bioterrorist attacks.

The recent attacks of September 11, 2001, and the subsequent dissemination event of anthrax in the United States demonstrated the necessity for hospitals to initiate bioterrorism education for clinicians. Events such as the release of sarin gas into the Tokyo subway by the Aum Shinrikyo cult provided some insight into how quickly emergency medical personnel may be overwhelmed by causalities of unconventional weapons. Educational interventions to prepare hospital-based practitioners for such disasters must fit among the demands of patient care, administrative duties, and continuing education within specialties. In addition, the priority placed on the topic, confusion about reputable resources to consult, and concerns of funding for preparedness training mandate the need for an authoritative, comprehensive, and easily accessible approach. A pilot project supported in part by the Agency for Healthcare Research and Quality was developed to facilitate streamlining of preparedness efforts through the implementation of interactive screen savers as an alternative to traditional educational modalities. This report presents the successful application of this model, which was quantified with pretests and posttests given to users of the system.

Bioterrorism↗
PubMed2002

A novel recombinant vaccine which protects mice against ricin intoxication.

Ricin toxin (RT) is a plant-derived toxin of extraordinary toxicity; a single molecule successfully internalized into the cytoplasm of a cell is lethal for that cell. An estimated dose of 1-10 microg/kg is lethal to humans, making aerosolized ricin a potential agent for bioterrorism. Vaccination against ricin using either denatured toxin or its modified A chain subunit (RTA) has been successful in experimental animals but both vaccines have potential toxicities. Recombinant (r) RTA has not been evaluated as a vaccine. However, the advantage of such a vaccine is that these potential toxicities can be deleted by appropriate mutations. In this study we have generated three mutants and shown that two lack toxicity as compared to the wild type rRTA. These mutants induce protective humoral immune responses in mice. One or both should be considered for use in humans.

Animals↗
PubMed2003

Bio-diversity: an effective safety net against environmental pollution.

Biodiversity is the feedstock for the biotechnology industry. Hence, the conservation, enhancement and sustainable and equitable use of biodiversity should be accorded high priority in all national environment protection programmes. Lichens serve as useful indicators of environmental health. Similarly, several blue green algae help to sequester salt from water. There is need for the more widespread use of such biomonitoring and bioremediation agents. Bioprospecting research designed to identify novel metabolites must be rooted in the principle of equity in sharing benefits with the holders of traditional knowledge. There is need for greater vigil against alien invasive species, since with growing world trade in food grains and other agricultural commodities, there is an increasing possibility of introducing new pests, weeds and harmful micro-organisms. Finally, biological scientists should place emphasis on their ethical responsibility for the consequences of their research, since otherwise bioterrorism could become a major threat to human security.

Animals↗
PubMed2005

[Glanders, melioidosis and biowarfare].

MANY COMMON FACTORS: Glanders and melioidosis are infectious diseases that are caused by the bacteria of the Burkholderia species. These infections are endemic in tropical regions and can lead to la broad spectrum of common clinical manifestations. TWO PRINCIPLE CLINICAL FORMS: The most frequent clinical presentation is the pulmonary form, which can mimic pulmonary tuberculosis. The septicemic form is the most severe form, and lethal in nearly 50% of cases. WEAPONS FOR BIOTERRORISM AND WAR: Very few organisms are required to cause disease by aerosolisation, which could be the main route of contamination for humans after a deliberate release. This property has permitted yet the use of these bacteria as biological warfare weapon during the past century. We have to consider these agents as possible biological warfare agents. Europeans guidelines for treatment and post-exposure prophylaxis are detailed.

Abscess↗
PubMedDate not supplied

A simple and rapid fluorescence-based immunoassay for the detection of staphylococcal enterotoxin B.

The bioterrorism threat is perceived to be a real challenge to our nation's security. This threat has necessitated the design of better and faster assays for the detection of biothreat agents including staphylococcal enterotoxin B (SEB), a causative agent of food poisoning. This study describes a simple, fast and highly sensitive fluorescence-based immunoassay, in which the antibody is fluorescently-labeled for use in this assay. Use of labeled antibodies resulted in very low level of detection of SEB, 100 pg/well. This method is four times faster than classical and conventional enzyme-linked immunosorbent assay (ELISA).

Bioterrorism↗
PubMed2002

The prophylaxis and treatment of anthrax.

Bacillus anthracis infection can occur in three forms: cutaneous, gastrointestinal and inhalation depending on the mode of infection. Anthrax is a zoonotic disease but the inhalation form can also be used as a biological warfare agent. The recent mail spread outbreak of bioterrorism-related infections in the USA prompted the introduction of specific guidelines by the USA Centers for Disease Control and Prevention. Postexposure prophylaxis is indicated to prevent inhalational anthrax, and therapy with ciprofloxacin or doxycycline is recommended for adults and children for 60 days. The same agents are also advocated for the treatment of inhalation anthrax. However, therapy with two or more antimicrobial agents that are predicted to be effective are recommended. Other agents with in vitro activity are also suggested for be use in conjunction with ciprofloxacin or doxycycline include rifampciin, vancomycin, imipenem, chloramphenicol, penicillin and ampicillin, clindamycin, and clarithromycin.

Anthrax↗
PubMed2003

Tripeptide inhibitors of Yersinia protein-tyrosine phosphatase.

The protein-tyrosine phosphatase (PTP) 'YopH' is a virulence factor of Yersinia pestis, the causative agent of plague. Potential use of Yersinia as a bioterrorism agent renders YopH inhibitors of therapeutic importance. Previously, we had examined the inhibitory potencies of a variety of phosphotyrosyl (pTyr) mimetics against the human PTP1B enzyme by displaying them in the EGFR-derived hexapeptide sequence, 'Ac-Asp-Ala-Asp-Glu-Xxx-Leu-amide', where Xxx=pTyr mimetic. The poor inhibitory potencies of certain of these pTyr mimetics were attributed to restricted orientation within the PTP1B catalytic pocket incurred by extensive peripheral interaction of the hexapeptide platform. Utilizing the smaller tripeptide platform, 'Fmoc-Glu-Xxx-Leu-amide' we demonstrate herein that several of the low affinity hexapeptide-expressed pTyr mimetics exhibit high PTP1B affinity within the context of the tripeptide platform. Of particular note, the mono-anionic 4-(carboxydifluoromethyl)Phe residue exhibits affinity equivalent to the di-anionic F(2)Pmp residue, which had previously been among the most potent PTP-binding motifs. Against YopH, it was found that all tripeptides having Glu residues with an unprotected side chain carboxyl were inactive. Alternatively, in their Glu-OBn ester forms, several of the tripeptides exhibited good YopH affinity with the mono-anionic peptide, Fmoc-Glu(OBn)-Xxx-Leu-amide, where Xxx=4-(carboxymethyloxy)Phe providing an IC(50) value of 2.8 microM. One concern with such inhibitors is that they may potentially function by non-specific mechanisms. Studies with representative inhibitors, while failing to provide evidence of a non-specific promiscuous mode of inhibition, did indicate that non-classical inhibition may be involved.

Algorithms↗
PubMed2004

Inhalational anthrax.

Anthrax remains a real threat. In a spore form, it is highly infectious and dispersible. The initial symptoms are similar to those of influenza, and the early stage of inhalational anthrax may not be recognized. Early antibiotic treatment is important to achieving a good outcome. Contrary to historical experience. many patients with even advanced anthrax can be saved with aggressive medical care. Prevention of anthrax infections requires vigilant infection control methods as well as a rational prophylactic plan. All health care providers should be familiar with the symptoms and treatment of this disease. It is hoped that future research will clarify tests for early diagnosis, the best methods of prophylaxis, and the most effective treatments. Unfortunately the threat of bioterrorism, and anthrax in particular, is unlikely to go away.

Anthrax↗
PubMed2004

Plague.

In the United States, plague poses a threat to humans from the infected animals in the endemic areas of the Western states. Plague may also be used in the near future as an agent of warfare or terrorism. Although the presentation of bubonic plague may be less of a problem, the septicemic and pneumonic forms present challenges to early diagnosis and prompt treatment. The major threat of plague as an agent of terrorism will probably be through the inhalational route. which could result in many cases of the pneumonic form, requiring early recognition and initiation of appropriate therapy. In a mass-casualty scenario, the clinician should be aware of the potential agents of biowarfare and be familiar with the treatment and prophylaxis recommendations outlined by the CDC. It is also prudent to employ universal precautions and respiratory isolation when treating patients with any unknown exposure. In endemic areas, personal protective measures such as use of insecticides, insect repellants, and prompt prophylaxis in cases of exposure to plague are recommended for reducing the incidence of infection. The author also recommends review of CDC website on bioterrorism (http://www.bt.cdc.gov) to keep informed of plague updates.

Bioterrorism↗
PubMed2003

Q fever: a biological weapon in your backyard.

Coxiella burnetii, which causes Q fever, is a highly infectious agent that is widespread among livestock around the world. Although the culture process for coxiella is laborious, large amounts of infectious material can be produced. If used as an aerosolised biological weapon, coxiella may not cause high mortality, but could provoke acute disabling disease. In its late course, Q fever can be complicated by fatal (eg, endocarditis) or debilitating (eg, chronic fatigue syndrome) disorders. The diagnosis of Q fever might be delayed because of non-specific and protean presentations. Effective antibiotic treatment is available for the acute form of disease but not for the chronic complications. Vaccination and chemoprophylaxis in selected individuals may be used in the event of bioterrorism.

Animals↗
PubMed2004

Human monkeypox: an emerging zoonosis.

Human monkeypox is a rare viral zoonosis endemic to central and western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. Although the natural animal reservoir of the monkeypox virus is unknown, rodents are the probable source of its introduction into the USA. A clear understanding of the virulence and transmissibility of human monkeypox has been limited by inconsistencies in epidemiological investigations. Monkeypox is the most important orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s. There is currently no proven treatment for human monkeypox, and questions about its potential as an agent of bioterrorism persist.

Adult↗